Taiwan International Graduate
Program
Molecular Medicine Program
Faculty
Institute of Biomedical Sciences /
National Yang ...
Taiwan International Graduate Program
Molecular Medicine Program
Institute of Biomedical Sciences
Faculty
2
Name in Chinese:張程
Name in English:Chang, Chen
Education: University of Alabama at Birmingham
Affiliation:Institute of Bio...
targeted technology development and imaging data analysis; (2) promote collaborative links between
the MR and basic scienc...
Name in Chinese:常蘭陽
Name in English:Lan-Yang Ch’ang
Education:Vanderbilt University
Affiliation:Institute of Biomedical Sc...
(1.) Functional Genomics
A complexity reduction technology has been developed for profiling the expressed genes in normal
...
differentiation of erythroleukemia K562 cells. J. Biomed. Sci. 11:104-111, 2004.
7
Name in Chinese:趙麗洋
Name in English:Chau, Lee-Young
Education:University of Kentucky
Affiliation:Institute of Biomedical S...
of HO-1. Furthermore, the therapeutic potential of HO-1 in treating cardiovascular diseases was
explored in animal models....
angiotension II-induced cardiac hypertrophy in vitro and in vivo. Circulation accepted
pending revision; 2004.
10
Name in Chinese:陳志成
Name in English:Chen, Chih-Cheng
Education:University College London, UK
Affiliation:Institute of Biom...
2. Pain behavior alteration of mice lack of proton-gated ion channel ASIC3
3. The roles of acid-sensing ion channels in se...
Name in Chinese:張久瑗
Name in English:Chen, Joanne Jeou-Yuan
Education:University of Minnesota
Affiliation:Institute of Biom...
various mRNA RDA, we have identified two thousands more genes that are differentially expressed in
GC. A gastric cancer ge...
Name in Chinese:陳士隆
Name in English:Chen, Steve S.-L.
Education:Purdue University
Affiliation:Institute of Biomedical Scie...
for designing a genetic, immunotherapeutic approach to controlling HIV-1 replication. Moreover, we
will examine whether ex...
cytoplasmic domain of human immunodeficiency type 1 virus transmembrane protein
gp41 on virus replication. J. Virol. 78:51...
Name in Chinese:陳垣崇
Name in English:Chen, Yuan-Tsong
Education:Columbia University
Affiliation:Institute of Biomedical Sci...
2). Functional characterization of a novel glucose transporter and its role in diabetes mellitus. We
cloned a novel glucos...
6. Chen, Y.T. Glycogen storage diseases. In: Harrison Principles of Internal Medicine,
14th Edition, pp 2176-2182, 1998, 1...
Name in Chinese:陳儀莊
Name in English:Chern, Yijuang
Education:University of Massachusetts
Affiliation:Institute of Biomedic...
in vivo. The principal objective of this research group is to understand the molecular mechanisms
underlying the physiolog...
terminus domain of type VI adenylyl cyclase (ACVI) in Gia-mediated inhibition. J.
Biol. Chem. (in press)
23
Name in Chinese:何美鄉
Name in English:Ho, Mei-Shang
Education: Indiana University
Affiliation:Institute of Biomedical Scienc...
recent years. The ongoing projects include establishing animal models to distinguish strain differences
in virulence; stud...
Sci. 11(2):239-248, 2004.
26
Name in Chinese:李旭東
Name in English:Lee, Sho Tone
Education: University of Manitoba, Canada
Affiliation:Institute of Biome...
Southeastern Asia. A C-terminal fragment of JEV envelope (E) protein was found to induce protective
immunity against JEV. ...
Name in Chinese:林天南
Name in English:Lin, Teng-Nan
Education:University of Missouri-Columbia
Affiliation:Institute of Biome...
1. Lin T-N, Wang PY, Chi SI, Kuo JS (1998) Differential regulation of ciliary neurotrophic
factor (CNTF) and CNTF receptor...
Name in Chinese:林文昌
Name in English:Lin, Wen-Chang
Education:Case Western Reserve University
Affiliation:Institute of Biom...
comparative proteomics in human dbEST data-mining efforts. With the CGI tool and human dbEST,
we have discovered over 500,...
5689.
9. Chun-Huang Lai, Chang-Yuan Chou, Lan-Yang Ch'ang, Chung-Shyan Liu, Wen-chang
Lin. 2000. Identification of Novel H...
Name in Chinese:潘文涵
Name in English:Pan, Wen-Harn
Education:Cornell University
Affiliation:Institute of Biomedical Science...
identified a novel splicing regulatory protein, RBM4, that antagonizes the activity of SR proteins in
splice site and exon...
and obesity-related metabolic disorders in Taiwanese and US whites and blacks:
implications for definitions of overweight ...
Name in Chinese:羅傅倫
Name in English:Roffler, Steve R.
Education: University of California, Berkeley
Affiliation:Institute ...
migration, adhesion and invasion of lung adenocarcinoma cells as well as in the regulation of
endothelial cell angiogenesi...
Biochem. Pharmacol., 66: 1181-1187, 2003.
39
Name in Chinese:謝如姬
Name in English:Shieh, Ru-Chi
Education:University of Rochester
Affiliation:Institute of Biomedical Sc...
Selected Recent Publication:
1. R-C Shieh. Mechanisms underlying the time-dependent decay of inward currents
through clone...
Name in Chinese:謝小燕
Name in English:Shieh, Sheau-Yann
Education:Baylor College of Medicine
Affiliation:Institute of Biomed...
have recently identified two cell cycle checkpoint kinases, hCHK1 and CHK2, as p53 kinases that
phosphorylate DNA damage-i...
2001.
44
Name in Chinese:徐松錕
Name in English:Shyue, Song-Kun
Education:Universityn of Texas-Houston
Affiliation:Institute of Biomed...
4. Using microarray and proteomic tools to study the constitutional types in Traditional
Chinese Medicine, such as hot and...
Cardiol. 36(1):129-39, 2004.
47
Name in Chinese:唐堂
Name in English:Tang, Tang k..
Education:Yale University
Affiliation:Institute of Biomedical Sciences, ...
mitosis and genomic instability.
B). Gene Regulation and Germ Cell Development
Spermatogenesis in mammals is a complex sys...
a novel microtubule-destabilizing motif in CPAP that binds to tubulin heterodimers and
inhibits microtubule assembly. Mol....
Name in Chinese:陶秘華
Name in English:Tao, Mi-Hua
Education: Columbia University
Affiliation:Institute of Biomedical Science...
also applied to engineer tumor antigens to generate more potent cancer vaccines.
2.Therapeutic Vaccines for Treatment of C...
Cancer 108: 696-703, 2004.
53
Name in Chinese:譚婉玉
Name in English:Tarn, Woan-Yuh
Education:National Tsing Hua University
Affiliation:Institute of Biomed...
splice site and exon selection5
. We also explore the molecular mechanisms of how transcription factors
control splicing r...
10. Lin, K. T., Leu, R. M. and Tarn, W. Y. The WW domain-containing proteins interact
with the early spliceosome and facil...
Name in Chinese:王寧
Name in English:Wang, Danny Ling
Education: University of Nevada
Affiliation:Institute of Biomedical Sc...
2. The molecular mechanisms of shear-induced protective effects in endothelial cells
3. The role of phosphatase(s) in endo...
Name in Chinese:顏裕庭
Name in English:Yan, Yu-Ting
Education: University of Medicine and Dentistry of New Jersey
Affiliation...
size, genetics, transgenics and reverse genetics or gene targeting. Targeted disruption of mouse Cryptic
results in L-R la...
Name in Chinese:楊瑞彬
Name in English:Yang, Ruey Bing Ray
Education:University of Texas Sounthwestern Medical Center at Dall...
methodologies as well as gene targeting approach to further evaluate their functions in the
cardiovascular, bone and repro...
mouse testis. Biochem. J. 379: 385-393, 2004.
63
Name in Chinese:嚴仲陽
Name in English:Yen, Jeffrey J.Y.
Education: Baylor College of Medicine
Affiliation:Institute of Biome...
profile of GATA family members and their target anti-apoptotic gene E4BP4, suggesting the survival
effect of GATA family p...
Name in Chinese:蕭百忍
Name in English:Yen, Pauline, H.
Education: University of California, Berkeley
Affiliation:Institute o...
elucidate their functions.
Selected Recent Publication:
1. Yen, P.H. Advances in Y-chromosome mapping. Curr. Opin. Obstet....
Taiwan International Graduate Program
Molecular Medicine Program
National Yang Ming University Faculty
68
Name in Chinese:張國威
Name in English:Kuo-Wei Chang
Education:1983, DDS, National Yang-Ming University
1995, PhD, Department...
6. Chang KW, Lin SC, Kwan PS and Wong YK* (2000) Association of p53/p21waf1
expression with
outcomes of veruccous leukopla...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
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Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...
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Molecular Medicine Program Faculty - 12/16/2009 04:39:55 pm ...

  1. 1. Taiwan International Graduate Program Molecular Medicine Program Faculty Institute of Biomedical Sciences / National Yang Ming University
  2. 2. Taiwan International Graduate Program Molecular Medicine Program Institute of Biomedical Sciences Faculty 2
  3. 3. Name in Chinese:張程 Name in English:Chang, Chen Education: University of Alabama at Birmingham Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3032, 886-2-2789-9027 Fax:886-2-2788-7641 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/cchang_c.htm E-mail:bmcchen@ibms.sinica.edu.tw Fields of Specialty: Functional MRI/S , Neuroscience Research Description: My research focus primarily on the development and application of magnetic resonance imaging and spectroscopy techniques for the study of brain metabolic, functional and structural alterations in a variety of cerebral diseases. Specific goals include: 1) developing and validating diffusion and perfusion MRI to evaluate the changes in cerebral hemodynamics as a result of brain damage; 2) combining BOLD-, diffusion tensor- and manganese- MRI to study the functional connectivity in rat brains; 3) developing molecular imaging techniques in studying specific biological pathways, and cell and gene therapy; 4) developing MR microscopy at cellular resolution to follow key intercellular and intracellular events; and 5) developing in vivo localized 1 H NMR spectroscopy to investigate the biochemical and physiological integrity of the brain. We have established a functional and micro-magnetic resonance imaging center (FMIC) core facility in 2002 to serve the Medical Genomics Program. The core is dedicated to: (1) provide state of the art MRI equipments and comprehensive MR technical support, including experimental design, 3
  4. 4. targeted technology development and imaging data analysis; (2) promote collaborative links between the MR and basic science research, and (3) educate and train researchers, fellows, and students in the use of MR imaging technologies in biomedical research. FMIC provides cutting-edge magnetic resonance techniques, emphasizing on providing anatomical, biochemical, functional, genetic and pharmacological information in vivo for small animals. Selected Recent Publication: 1. Chang, C. and Shyu, B. C. A fMRI Study of Brain Activations During Non-noxious and Noxious Electrical Stimulatiion of the Sciatic Nerve of Rats. Brain Res., 2001; 897:71- 81.. 2. Sun, S. W.; Song, S. K.; Hong, C. Y.; Chu, W. C.; and Chang, C. Improving Relative Anisotropy Measurement using Directional Correlation of Diffusion Tensors. Mag. Reson. Med., 2001; 46:1079-1087. 3. Lin, T. N.; Sun, S. W.; Cheung, W. M.; Li, Fuhai and Chang C. Dynamic Changes in Cerebral Blood Flow and Angiogenesis after Transient Focal Cerebral Ischemia in Rats: Evaluation with Serial MRI. Stroke, 2002; 33: 2985 - 2991. 4. Song, S.K.; Sun, S.W.; Ramsbottom, M.J.; Chang, C.; Russell, J. and Cross, H. Dysmyelination Revealed through MRI as Increased Radial (But Unchanged Axial) Diffusion of Water. NeuroImage, 2002; 17:1429-1436. 5. Sun, S. W.; Song, S. K.; Hong, C. Y.; Chu, W. C.; and Chang, C. Directional correlation characterization and classification of white matter tracts: Magn. Reson. Med. 2003; 49:271-275. 6. Lee, W. T. and Chang, C. Magnetic Resonance Imaging and Spectroscopy in Assessing 3- Nitropropionic Acid-Induced Brain Lesions: Animal Model of Huntington's Disease. Progress in Neurobiology 2004, 72:87-110. 7. Shyu, B.C.; Lin, C. Y.; Sun, J.J.; Chen, S. L. and Chang, C. BOLD response to direct thalamic stimulation reveals functional connection of the medial thalamus and anterior cingulate cortex in the rat. Magn. Reson. Med (in press). 8. Shyu, B.C.; Lin, C. Y.; Sun, J.J.; Chen, S. L.; Sylantyeva, S.and Chang, C. A method for direct thalamic stimulation in fMRI studies using a glass-coated carbon fiber electrode. J. Neuro. Methods (in press). 4
  5. 5. Name in Chinese:常蘭陽 Name in English:Lan-Yang Ch’ang Education:Vanderbilt University Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3940, 886-2-2789-9128 Fax:886-2-2785-8847 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/lychang_c.html E-mail:lychang@ibms.sinica.edu.tw Fields of Specialty:Genomics, Bioinformatics Research Description: Our research objective is to dissect the complexity of human biology from the perspectives of genome, transcriptome and proteome. It is thus of critical importance to establish in the laboratory appropriate technological competence that enables the study of large-scale biology. The ultimate goal of this undertaking is to understand better how the complex genetic networks operate and govern all aspects of biological processes in living organisms. The human genomic sequence, completed in 2003, provides us a genetic framework for examining the complexity of life. The functionality of each annotated gene will be described in the context of its biological role under normal physiology or in response to external factors. In the revolutionary era of new biology, this knowledge foundation will greatly assist us to identify genes involved in various disease processes for future development of diagnostic, therapeutic and preventive measures. Our ongoing research efforts cover three major areas of interest: 5
  6. 6. (1.) Functional Genomics A complexity reduction technology has been developed for profiling the expressed genes in normal and diseased conditions, and during early embryogenesis. DNA microarray has also been set up for the analysis of gene expression pattern. Recently we have begun to characterize the function of novel genes in the human genome by the molecular and cellular approaches as well. (2) Bioinformatics We have developed an alternative algorithm –CRASA– for mapping the expressed sequence tags (ESTs) to the genome, which enables us to annotate the transcribed sequence in the public databases. A fully automated gene annotation pipeline has been established for large-scale EST-to- genome mapping. In addition we are in process of developing a new algorithm for the identification of evolutionarily conserved syntenic markers in the mammalian genomes. (2.) Human Genetic Diversity Sequence variation among different individuals accounts for 0.1% of our genomic content. Yet, the biological consequence, or phenotype, is often dictated by the polymorphic genotypes functioning alone or interacting with environmental factors. Currently, we are developing a haplotyping technique to address the correlation between genotype and phenotype using the human disease model. Selected Recent Publication: 1. J.-Y. Chiu, C.-S. Liu, L.-Y. Ch'ang and W.-C. Lin. Comparative Ping-pong Analysis of EST Databases. J. Genet. & Mol. Biol. 2:94-100, 2002. 2. S.-J. Wei, W.-K. Yang, L.-Y. Ch'ang, D.-M. Yang, Y.-M. Hung and W.-C. Lin. Combination Gene Therapy of Cancer: Granulocyte-Macrophage Colony Stimulating Factor Enhances Tumor Regression Induced by Herpes Simplex Virus Thymidine Kinase/ Ganciclovir "Suicidal" Treatment in a Mouse Tumor Model. J. Genet. & Mol. Biol. 3:194- 208, 2002. 3. T.-J. Chuang, W.-c. Lin, H.-C. Lee, C.-W. Wang, K.-L. Hsiao, Z.-H. Wang, D. Hsieh, S.C. Lin and L.-Y. Ch'ang. A Complexity Reduction Algorithm for Analysis and Annotation of Large Genomic Sequence. Genome Res. 13:313-322, 2003 4. Lin, T.-Y., Twu, N.-K., Ho, M.-S., Ch'ang, L.-Y., and Lee, C.-Y. Enterovirus 71 outbreak, Taiwan: occurrence and recognition. J. Emerging Inf. Dis. 9:291-293, 2003. 5. Liu, C.C. and Ch'ang, L.-Y. Down-regulation of human NDR gene in megakaryocytic 6
  7. 7. differentiation of erythroleukemia K562 cells. J. Biomed. Sci. 11:104-111, 2004. 7
  8. 8. Name in Chinese:趙麗洋 Name in English:Chau, Lee-Young Education:University of Kentucky Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3931, 886-2-2789-9137 Fax:886-2-2785-8847 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ lychau_c.html E-mail:lyc@ibms.sinica.edu.tw Fields of Specialty:Cardiovascular Diseases, Inflammation, Gene therapy Research Description: Cardiovascular diseases are the leading cause of morbidity and mortality in developed countries. As the worldwide incidence of cardiac diseases continues to increase steadily, fully understanding the pathological mechanisms underlying the disease development at the molecular and genetic levels as well as developing new successful approaches for the therapeutic intervention imposes a great challenge in biomedical research nowadays. The research interests in my laboratory include the development of gene-based therapeutic treatment for the diseases, and the identification of disease- related genes using ENU-mutagenesis approach. Besides, we are very interested in the study of the cytoprotective function of heme oxygenase-1 (HO-1), which is a stress-inducible enzyme to catalyze the degradation of prooxidant heme to produce carbon monoxide (CO), bilirubin and free iron. Recent studies from our liaboratory and others have demonstrated that HO-1 plays an important role in iron homeostasis and exerts potent anti-inflammatory effect via CO, although the mode of action is not yet clear. Experiments are ongoing to elucidate the signaling network underlying the protective function 8
  9. 9. of HO-1. Furthermore, the therapeutic potential of HO-1 in treating cardiovascular diseases was explored in animal models. Selected Recent Publication: 1. Lee T-S., Yen, H-C., Pan, C-C. and Chau, L-Y. The role of interleukin 12 in the development of atherosclerosis in apoE-deficient mice. Arterioscler. Thromb. Vasc. Biol. 19: 734-742, 1999. 2. Pang, J-H.S. and Chau, L-Y. Copper-induced apoptosis and immediate early gene expression in murine J774.A1 macrophages. Atherosclerosis. 146: 45-52, 1999. 3. Ai, L-S. and Chau, L-Y. Post-transcriptional regulation of H-ferritin mRNA: Identification of a pyrimidine-rich sequence in 3'-untranslated region associated with message stability in human monocytic THP-1 cells. J. Biol. Chem. 274: 30209-30214, 1999. 4. Lee, T-S. and Chau, L-Y. Fas/Fas ligand-mediated pathway is involved in oxidized LDL-induced apoptosis in vascular smooth muscle cells. Am. J. Physiol.Cell Physiol. 280: C709-C718, 2001. 5. Juan, S-H., Lee, T-S., Tseng, K-W., Liou, J-Y., Shyue, S-K., Wu, K-K. and Chau, L-Y. Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apoE-deficient mice. Circulation 104, 1519-1525, 2001. 6. Lee, T-S. and Chau, L-Y. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat. Med. 8, 240-246, 2002. 7. Chen, Y-H., Lin, S-J., Lin, M-W., Tsai, H-L., Kuo, S-S., Chen, J-W., Charng, M-J., Wu, T-C., Chen, L-C., Ding, P.Y-A., Pan, W-H., Jou, Y-S., and Chau, L-Y. Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients. Hum. Genet. 111:1-8; 2002 8. Lee, T-S., Tsai, H-L., and Chau, L-Y. Induction of heme oxygenase-1 expression in muirne macrophages is essential for the anti-inflammatory effect of low dose 15-deoxy- 12,14-prostaglandin J2. J. Biol. Chem. 278:19325-19330; 2003.△ 9. Chen, Y-H, Chau, L-Y, Lin, M-W, Chen, L-C, Yo, M-H, Chen, J-W, and Lin, S-J. Heme oxygenase-1 gene promotor microsatellite polymorphism is associated with angiographic restenosis after coronary stenting. Eur Heart J. 25:39-47; 2004. 10.Hu, C-M., Chen, Y-H., Chiang, M-T., and Chau, L-Y. Heme oxygenase-1 inhibits 9
  10. 10. angiotension II-induced cardiac hypertrophy in vitro and in vivo. Circulation accepted pending revision; 2004. 10
  11. 11. Name in Chinese:陳志成 Name in English:Chen, Chih-Cheng Education:University College London, UK Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Assistant Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3917, 886-2-2789-9057 Fax:886-2-2782-9224 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ccchen_c.html E-mail:chih@ibms.sinica.edu.tw Fields of Specialty: Pain, Neurobiology, Gene Targeting, Mouse Genetics Research Description: Acid (protons) is one of the major factors in pain sensation. High concentrations of protons or tissue acidosis occur in pain associated with inflammation, ischemia, tumors, etc. Therefore, the study of genes involved in acid signaling will be beneficent to the development of new analgesic drugs. We have cloned a few acid-sensing ion channels (ASICs) from sensory neurons and generated ASIC3 knockout and transgenic mice. From the study of ASIC3 knockout mice, we have confirmed that ASIC3 is involved in pain sensation. In many nociceptive tests, we found that mice lack of the ion channels showing hyperalgesic behaviors. This result was surprising but provided us a new insight of role of protons, which may be involved in many different physiological functions. Thus, we will continue screening and cloning the receptor genes for protons, as well as studying their roles in pain sensation and other physiological functions by using transgenic and knockout mice models. Specific projects include: 1. Transgenic & knockout mouse model of human familial disautonomia. 11
  12. 12. 2. Pain behavior alteration of mice lack of proton-gated ion channel ASIC3 3. The roles of acid-sensing ion channels in sensory neurons. 4. Genetic mapping and molecular cloning of genes involved in acid-signaling and nociception Selected Recent Publication: 1. Chen, C.-C., Zimmer, A.M., Sun, W.H., Hall, J.E., Brownstein, M.J., and Zimmer, A. (2002). A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc. Natl. Acad. Sci. USA 99, 8992-8997. 2. Akopian, A.N., Chen, C.-C., Ding, YN., Cesare, P., and Wood, J.N. (2000). A new member of the acid-sensing ion channel family. Neuroreport 11, 2217-2222. 3. Akopian, A.N., Chen, C.-C., Souslova, V., Okuse, K., and Wood, J.N. (2000). Sensory neuron-specific ion channels and receptors. In: Molecular Basis of Pain Induction, ed Wood, J.N., Wiley-Liss Inc., pp.113-128 4. Chen, C.-C., England, S., Akopian, A.N., and Wood, J.N. (1998). A sensory neuron- specific, proton-gated ion channel. Proc. Natl. Acad. Sci. USA 95, 10240-10245. 5. Krylova, O., Chen, C.-C., Akopian, A., Souslova, V., Okuse, K., Abson, N., Ravenal, S., and Wood, J.N. (1997). Ligand-gated ion channels of sensory neurons: from purines to peppers. Biochemical Society Transactions 25, 842-844. 6. King, B., Chen, C.-C., Akopian, A.N., Burnstock, G., and Wood, J.N. (1997). A role for calcineurin in the desensitisation of P2X3. Neuroreport 8, 1009-1102. 7. Chen, C.-C., Akopian, A.N., Sivilotti, L., Colquhoun, D., Burnstock, G., and Wood, J.N. (1995). A P2X purinoceptor expressed by a subset of sensory neurons Nature 377, 428- 431. 8. Hsu, Y.L., Chen, C.-C., and Wu, J.L. (1995). Molecular relationships in infectious pancreatic necrosis virus. Virus Research 37, 239-252. 12
  13. 13. Name in Chinese:張久瑗 Name in English:Chen, Joanne Jeou-Yuan Education:University of Minnesota Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3966, 886-2-2789-9046 Fax:886-2-2785-8594 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/jychen_c.html E-mail:bmchen@ibms.sinica.edu.tw Fields of Specialty:Cancer Genomics, Molecular and Tumor Biology Research Description: A major problem in the management of patients with cancer is the lack of specific tumor markers for the early detection, the accurate prediction of the biological behavior and the accurate assessment of prognosis. The identification of tumor-associated candidate genes provides an answer to this problem. Gastric cancer (GC) is highly prevalent. To systematically dissect the pathways that are involved in the initiation and progression of this disease, various approaches of representational difference analysis (RDA) have been taken to isolate gastric cancer-associated genes. By genomic RDA, chromosomal instability and microsatellite instability have been determined in GC at a genome- wide level. A subset of GC was characteristic of high microsatellite instability as the result of mutations in mismatch repair genes. In other GCs, distinct patterns of chromosomal instability and DNA copy number changes are tightly associated with specific clinicopathologic features. Candidate gene approach is underway to further explore he regions that may harbor candidate oncogenes or tumor suppressor genes dominating the pathogenic development of specific subtypes of GC. By 13
  14. 14. various mRNA RDA, we have identified two thousands more genes that are differentially expressed in GC. A gastric cancer gene chip based on the cDNA of these genes was established and microarray hybridization was performed followed by cluster analyses to identify candidate genes associated with the pathogenic development of GC of specific histopathologic subtypes and stages. Genes that are involved in various pathways regulating cell proliferation or survival are focused and the potential usage of them as molecular markers for GC patients is evaluated. By proteomics, we are using humoral antibodies elicited in the sera of GC patients as reagents to isolate tumor antigens, with the hope to identify overexpressed candidate genes that may play important roles in gastric tumorigenesis. The goals of these studies are to provide a broad scope of the genetic events that are involved in the pathogenic development of gastric adenocarcinoma, with the hope to establish better choices of useful diagnostic and prognostic markers, and in the long run, to provide us the common denominator for understanding, treating, and preventing this disease. Selected Recent Publication: 1. Lo, P.-K., Chen, J.-Y., Tang, P.-P., Lin, J., Lin, C.-H., Su, L.-T., Wu, C.-H., Chen, T.-L., Yang, Y. and Wang, F.-F.* Identification of a mouse thiamine transporter gene as a direct transcriptional target for p53. J. Biol. Chem. 276: 37186-37193, 2001. 2. Wu, C.-W., Chen, G.-D., Fann, C. S.-J., Lee, A. F.-Y., Chi, C.-W., Liu, J. M., Weier, U. and Chen, J.-Y.* Clinical implications of chromosomal abnormalities in gastric adenocarcinomas. Genes, Chromosomes and Cancer. 35:219-231, 2002. 3. Huang, C.-J. and Chen, J.-Y.* Identification of Additional IE2-p86-responsive Cis- repressiive Sequences within the Human Cytomegalovirus Major Immediate Early Promoter. J. Biomed. Sci. 9:460-470, 2002. 4. Fann, C. S.-J., Chen, J.-Y.*, Wu, C.-W., and Chi, C.-W. Regarding clinical implications of chromosomal abnormalities in gastric adenocarcinomas. Genes, Chromosomes, and Cancer 38:204-206, 2003. 5. Kao, C.-F., Chen, S.-Y., Chen, J.-Y., and Lee, Y.-H. W.* Modulation of p53 Transcription Regulatory Activity and Posttranslational Modification by Hepatitis C Virus Core Protein. Oncogene (In press), 2004. 6. Liu, C.-A., Wang, M.-J., Chi, C.-W., Wu, C.-W., and Chen, J.-Y.* Overexpression of Rho Effector Rhotekin Confers Increased Survival in Gastric Adenocarcinoma. J. Biomed. Sci. (In press), 2004. 14
  15. 15. Name in Chinese:陳士隆 Name in English:Chen, Steve S.-L. Education:Purdue University Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3933, 886-2-2789-9035 Fax:886-2-2785-8847 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/slchen_c.html E-mail:schen@ibms.sinica.edu.tw Fields of Specialty:Retrovirology, Virus-host Interactions, Viral Protein Functions, Viral Pathogenesis Research Description: Our current research focuses on HIV-1 viral protein functions, viral protein-protein interactions underlying viral pathogenesis, and on the development of genetic anti-HIV strategies. In the Gag project, we recently demonstrated a novel mode of trans-dominant inhibition in HIV-1 replication by a cytoplasmic domain fusion protein β-gal/706-856. We aim to further understand the molecular, viral, and cellular bases for the role of this inhibitor in modulation of Gag and Env expression. In the Env project, we intend to examine the role of palmitoylation of the Env cytoplasmic domain in viral replication and Env targeting to lipid rafts, and to understand the biological functions of the putative cholesterol-binding motif located in the ectodomain of gp41. In a new SARS coronavirus project, we intend to characterize the biological functions of the heptad repeat (HR)1, and HR2 motifs in the spike protein in virus replication. In the gene transfer and therapy program, we attempt to understand whether IL10, which was known to downregulate HIV-1 replication in vitro, can be used as a candidate 15
  16. 16. for designing a genetic, immunotherapeutic approach to controlling HIV-1 replication. Moreover, we will examine whether expression of a cytoplasmic tail fragment and β-gal/706-856 in lentiviral vector- transduced human CD4+ T cells and primary cells can inhibit HIV-1 replication. Selected Recent Publication: 1. Lee, S.-F., Wang, C.-T., Liang, J. Y.-P., Hong, S.-L., Huang, C.-C. and Chen, S. S.-L. Multimerization potential of the cytoplasmic domain of the human immunodeficiency virus type 1 transmembrane glycoprotein gp41. J. Biol. Chem. 275: 15809-15819, 2000. 2. Wang, C.-T., Chen, S. S.-L., and Chiang, C.-C. Assembly and release of human immunodeficiency virus type 1 Gag proteins containing tandem repeats of the matrix protein coding sequences in the matrix domain. Virology 278: 289-298, 2000. 3. Chiou, S.-H., Liu, J.-H., Hsu, W.-M., Chen, S. S.-L., Chang, S.-Y., Juan, L.-J., Lin, J.- C., Yang, Y.-T., Wong, W.-W., Liu, C.-Y., Lin, Y.-S, Liu, W.-T., and Wu, C.-W. Upregulation of Fas ligand expression by human cytomegalovirus immediate-early gene 2: a novel mechanism in CMV-induced apoptosis in human retina. J. Immnol. 167: 4098- 4103, 2001. 4. Chen, S. S.-L., Lee, S.-F., and Wang, C.-T. Cellular membrane-binding ability of the C- terminal cytoplasmic domain of human immunodeficiency virus type 1 envelope transmembrane protein gp41. J. Virol. 75: 9925-9938, 2001. 5. Lee, S.-F., Ko, C.-Y., Wang, C.-T., and Chen, S. S.-L. Effect of point mutations in the N-terminus of the lentivirus lytic peptide-1 sequence of human immunodeficiency virus type 1 transmembrane protein gp41 on Env stability. J. Biol. Chem. 277: 15363-15375, 2002. 6. Hsu, W.-M., Chen, S. .S.-L., Peng, C.-H., Chen, C.-F., Ko, Y.-C., Tsai, D.-C., Chou, C.- K., Ho, L.-L., Chiou, S.-H., and Liu, J.-H. Elevated nitric oxide level in aqueous humor of AIDS patients with cytomegalovirus retinitis. Ophthalmologica 217: 298-301, 2003. 7. Chen, S.-W., Chiu, H.-C., Liao, W.-H., Wang, F.-D., Chen, S. S.-L., and Wang, C.-T. The virion-associated human immunodeficiency virus type 1 Gag-Pol carrying an active protease domain in the matrix region is severely defective both in autoprocessing and in trans processing of gag particles. Virology 318: 534-541, 2004. 8. Chan, W.-E., Wang, Y.-L., Lin, H.-H., and Chen, S. S.-L. Effect of extension of the 16
  17. 17. cytoplasmic domain of human immunodeficiency type 1 virus transmembrane protein gp41 on virus replication. J. Virol. 78:5157-5159, 2004. 17
  18. 18. Name in Chinese:陳垣崇 Name in English:Chen, Yuan-Tsong Education:Columbia University Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Distinguished Research Fellow/ Director, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3001, 886-2-2789-9104 Fax:886-2-2782-5573 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ytchen_c.htm E-mail:chen0010@ibms.sinica.edu.tw Fields of Specialty:Human Genetics, Genomic Medicine Research Description: Our overall research interests are in translational research. We aim at translating the promise of genomic medicine into clinical reality. Specific projects at present time include: 1). Identification of novel genes/targets associated with human diseases. This includes susceptibility genes for common multi-factorial diseases and pharmacogenetic disorders and disease causing genes for single gene disorders. Genetic epidemiology, mouse ENU mutagenesis, bioinformatics and proteomics are some approaches that we use in identification of novel genes associated with the human disease. Genes for several monogenic diseases have been mapped and/or identified. Genetic markers associated with drug-induced Stevens-Johnson syndrome have been identified. A systematic, genome-wide, phenotype-driven mutagenesis program for gene function studies in the mouse have resulted in the identification of a mouse model resembling human maple syrup urine disease. We will continue our research along these lines to identify more novel disease genes/ targets and to increase our understanding of the diseases. 18
  19. 19. 2). Functional characterization of a novel glucose transporter and its role in diabetes mellitus. We cloned a novel glucose transporter (Glu 10), which is highly expressed in pancreas and liver and is located on a region of a chromosome where a diabetes mellitus type II locus has been mapped. We are currently investigating its role in diabetes by generation of knock out mouse model and by direct genetic association study of human patients affected with diabetes. 3). Enzyme and gene therapy and targeting mechanisms of Pompe disease. Pompe disease is a fatal genetic muscle disorder. As enzyme replacement therapy for Pompe disease moves into clinical trials the fundamental question of how the enzyme targets the heart and skeletal muscle remains unanswered. In vitro studies have established that the uptake of the enzyme in cultured fibroblasts is due to receptor-mediated endocytosis via the mannose-6-phosphate receptor (MPR300), however, it is presently unclear if the same system is involved in vivo. We have generated tissue-specific MPR300 knockout mouse model to help us answer this question and to better define the role of the receptor in vivo. In anticipation of expanding the clinical trial to adult and juvenile patients, we are also evaluating what effects advanced age may have upon the efficacy of the enzyme and gene therapy using animal models. Selected Recent Publication: 1. Sun BD, Chen Y-T, Bird A, Amalfitano A, Koeberl DD. Long-term correction of glycogen storage disease type II with a hybrid adenovirus-adeno-associated virus vector. Mol Ther 7:193-201, 2003. 2. Wu JY, Kao HJ, Li SC, Stevens RD, Hillman S, Millington DS, and Chen YT. ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease. J Clin Invest, 113:434-440, 2004. 3. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JW, Chen YT. A marker for Stevens-Johnson syndrome. Nature, 428:486 2004. 4. Quan H, Athirakul K, Westle, WC, Torres, GE, Stevens R, Chen YT, Coffman TM, Caron MG. Hypertension and impaired glycine handling in mice lacking the orphan transporter XT2. Molecular & Cellular Biology, 24: 4166-4173, 2004. 5. Hwu WL, Yang CF, Fann Cathy S J, Chen CL, Tsai TF, Chien YH, Chiang SC, Chen CH, Hung SI , Wu JY, and Chen YT. Mapping of psoriasis to 17q terminus. J Medical Genetics, in press, 2004. 19
  20. 20. 6. Chen, Y.T. Glycogen storage diseases. In: Harrison Principles of Internal Medicine, 14th Edition, pp 2176-2182, 1998, 15th Edition, pp 2281-2289, 2001, 16th edition, in press 2004. 20
  21. 21. Name in Chinese:陳儀莊 Name in English:Chern, Yijuang Education:University of Massachusetts Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3913, 886-2-2789-9028 Fax:886-2-2782-9143 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ychern_c.html E-mail:bmychern@ccvax.sinica.edu.tw Fields of Specialty:Signal Transduction , Gene Regulation Research Description: We previously cloned the cDNA and the gene of the rat A2A adenosine receptor (A2A-R), which contains seven transmembrane domains and belongs to the G protein-coupled receptor family. Stimulation of A2A-R results in activation of adenylyl cyclase/protein kinase A (PKA) and protein kinase C (PKC). One of A2A-R’s physiological functions is to protect cells against various assaults. Using PC12 as a neuron-like model system, we demonstrated that atypical PKCs function downstream of PKA to mediate the protective effect of the A2A-R against apoptosis evoked by serum withdrawal in PC12 cells. In addition, A2A-R stimulation rescued the blockage of NGF-induced neurite outgrowth when the NGF-evoked MAPK cascade was suppressed. In the central nervous system (CNS), the A2A- R gene is heavily expressed in GABAergic striopallidal neurons, which selectively degenerate during progression of Huntington’s disease (HD). We therefore are investigating the potential therapeutic effects of A2A-R-selective agonists on HD using a transgenic mouse model (R6/2) of HD. Moreover, we also are using cellular and transgenic approaches to study the gene regulation and function of A2A-R 21
  22. 22. in vivo. The principal objective of this research group is to understand the molecular mechanisms underlying the physiological functions and the regulation of A2A-R. Selected Recent Publication: 1. Liu, F.C., Wu, G.C., Hsieh, S.T., Lai, H.L., Wang, H.F., Wang, T.W. and Chern, Y. Expression of type VI adenylyl cyclase in the central nervous system: implication for a potential regulator of multiple signals in different neurotransmitter systems. FEBS Lett. 436: 92-98, 1998. 2. Lai, H.L., Lin, T.H., Kao, Y.Y., Lin, W.J., Hwang, M.J. and Chern, Y. The N terminal domain of type VI adenylyl cyclase mediates its inhibition by protein kinase C. Mol. Pharmacology 56: 644-650, 1999. 3. Lee, Y.C., Chang, C.W., Su, C.W., Lin, T.N., Sun, S.H., Lai, H.L. and Chern, Y. The 5' untranslated regions of rat A2A adenosine receptor gene function as negative translational regulators. J. Neurochem. 73: 1790-1798, 1999. 4. Chern, Y. Regulation of adenylyl cyclase in the central nervous system. Cellular Signalling 12: 195-204, 2000. 5. Huang, N.K., Lin, Y.W., Huang, C.L., Messing, R.O. and Chern, Y. Activation of protein kinase A and atypical protein kinase C by A2A adenosine receptors antagonizes apoptosis due to serum deprivation in PC12 cells. J. Biol. Chem. 276: 13838-13846, 2001. 6. Wu, G.C., Lai, H.L., Lin, Y.W., Chu, Y.T. and Chern, Y. N-glycosylation and residues Asn805 and Asn890 are involved in the functional properties of type VI adenylyl cyclase. J. Biol. Chem. 276: 35450-35457, 2001. 7. Lin, T.H., Lai, H.L., Kao, Y.Y., Sun, C.N., Hwang, M.J. and Chern, Y. Protein kinase C inhibits type VI adenylyl cyclase (ACVI) by phosphorylating the regulatory N domain and two catalytic C1 and C2 domains. J. Biol. Chem. 277: 15721-15728, 2002. 8. Lee Y.-C., Chien C.-L., Sun C.-N., Chiang, M. C., Huang C.-L., Huang N.-K., Lai H.- L., Lin Y.-S., Chiou S.-Y., Liao W.-L., Liu F.-C., Wang L., Tai M.-H., Lin T.-N. and Chern Y. Characterization of the rat A2A adenosine receptor gene: a 4.8-kb promoter- proximal DNA fragment confers selective expression in the central nervous system. Eur. J. Neurosci. 18: 1786- 1796,2003. 9. Kao, Y.Y., Lai, H.L., Hwang, M.J. and Chern, Y. An important functional role of the N 22
  23. 23. terminus domain of type VI adenylyl cyclase (ACVI) in Gia-mediated inhibition. J. Biol. Chem. (in press) 23
  24. 24. Name in Chinese:何美鄉 Name in English:Ho, Mei-Shang Education: Indiana University Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3045, 886-2-2789-9120 Fax:886-2-2782-3047 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ msho_c.html E-mail:homs@ibms.sinica.edu.tw Fields of Specialty:Epidemiology ,Virology. Research Description:. Probing into the biological basis that renders the wide spectrum of clinical outcomes of microbial infections represents one of the most intriguing aspects in clinical practice and research in infectious diseases. It is generally contended that the interplay between hosts and micriobes contributes to the main thrust in steering an infectious process towards a certain clinical outcome, i.e., the microbial virulent or attenuated genes/factors vis-a- vis host 掇 susceptible factors derived at the genetic level or during the process of immunological response. The central themes in our laboratory are revolved around queries into precisely the above question by studying two infection models: hepatitis B virus (HBV) and enterovirus 71. For HBV investigation, our focus is on vaccine-related issues with emphasis on vaccine failure and chronic HBV infection of vaccines. The ongoing projects include study of genetic predisposition for chronic infection by the immune escape mutants and study of human susceptible genes for HBV infection by genetic epidemiological approach. Enterovirus 71 - the newly identified neurotropic enteroviruse, is epidemic prone in causing morbidity and mortality in 24
  25. 25. recent years. The ongoing projects include establishing animal models to distinguish strain differences in virulence; studying the molecular basis for viral virulence by infectious clones derived from reverse genetic technology, therefore, the host-virus interaction can be further studied by series of in vivo experiments using mutant and chimera virus in conjunction with knock-out mice. Furthermore, we are identifying the mammalian cellular receptors for enterovirus 71 which would provide basis for establishment of a susceptible transgenic mice model for enterovirus 71 in vivo study. Selected Recent Publication: 1. Ho, M.S., Mau, Y.C., Lu, C.F., Huang, S.F., Hsu, L.C., Lin, S.R. and Hsu, H.M. Patterns of circulating hepatitis B surface antigen variants among vaccinated children born to hepatitis B surface antigen carrier and non-carrier mothers. Journal of Biomedical Science 5: 355-362, 1998. 2. Shih, S.R., Ho, M.S., Lin, K.H., Wu, S.L., Chen, Y.T., Wu, C.N., Lin, T.Y., Chang, L.Y., Tsao, K.C., Ning, H.C., Chang, P.Y., Jung, S.M., Hsueh, C. and Chang, K.S.Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in Taiwan, 1998. Virus Research 68: 127-136, 2000. 3. Wu, C.N., Lin, Y.C., Fann, C., Liao, N.S., Shih, S.R. and Ho, M.S. Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1 accines and inactivated virus. Vaccine 20: 895-400, 2002. 4. Lin, Y.C., Wu, C.N., Shih, S.R. and Ho, M.S. Characterization of a vero cell-adapted virulent strain of enterovirus 71 suitable for use as a vaccine candidate. Vaccine 2002. 5. Ho, M.S., Chiu, L.Y., Lin, Y.C., Hu, C.Y., Lee, T.D., Fann, C.S.J., Tsai, J.F. and Chen, D.S. Genetic predisposition to chronic hepatitis B infection in vaccinated children with emphasis on immune escape variants. J. Med. Virology 2002. 6. Lin, Y.-C., Wu, C.-N., Shih, S.-R. and Ho, M.-S. Characterization of a vero cell-adapted virulent strain of enterovirus 71 suitable for use as a vaccine candidate. Vaccine 20, 2485-2493, 2002. 7. Lin, T.-Y., Twu, S.-J., Ho, M.-S., Ch'ang, L.-Y. and Lee, C.-Y. Enterovirus 71 outbreak, Taiwan: occurrence and recognition. J. Emerging Infectious Disease 9:291-293, 2003. 8. Shih, S.-R., Chiang, C., Chen, T.-C., Wu, C.-N., Hsu, J.-T., Lee, J.-C., Hwang, M.-J.,Li, M.-L., Chen, G..-W. and Ho, M.-S. Mutations at KFRDI and VGK domains of enterovirus 71 3C protease affect its RNA binding and proteolytic activities. J. Biomed. 25
  26. 26. Sci. 11(2):239-248, 2004. 26
  27. 27. Name in Chinese:李旭東 Name in English:Lee, Sho Tone Education: University of Manitoba, Canada Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3935, 886-2-2789-9170 Fax:886-2-2785-8847 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/stlee_c.html E-mail:bmtom@ccvax.sinica.edu.tw Fields of Specialty: Drug Resistance ,Vaccine Development Research Description: As a member of the Division of Infectious Diseases, our laboratory focuses our effort on two topics: (1) study of the mechanism of genesis of drug resistance and gene amplification in protozoan Leishmania parasites and the mechanism(s) of infection of Leishmania parasite to host mononuclear phagocytes and (2) development of subunit and DNA vaccines against flavivirus. In drug resistance: (i) a genome wide search of the genes activated during resistance induction in order to understand the mechanisms of genesis behind drug resistance and gene amplification. Subtractive hybridization and proteomic approaches are used for a genome wide comparison between the wildtype and the drug-resistant Leishmania; (ii) an intercellular adhesive molecule (ICAM) cloned and expressed is used to investigate the mechanism involved in the interaction between the parasite and its host macrophage. In the flaviral vaccine study, we focus on the development of subunit and DNA vaccines against Japanese encephalitis virus (JEV) which is an important pathogen in Taiwan as well as in Eastern and 27
  28. 28. Southeastern Asia. A C-terminal fragment of JEV envelope (E) protein was found to induce protective immunity against JEV. We are now mapping the smallest and most immunodominant fragment of this antigen for inducing protective immunity against JEV using DNA priming-protein boosting strategies. Selected Recent Publication: 1. Singh, A.K. and Lee, S.T. Status of respiration and ATP content in arsenite resistant Leishmania mexicana amazonensis. Microbiol. Pathogen. 26(3): 171-174, 1999. 2. Lye, L.F., Chiang, S.C., Hsu, J.Y. and Lee, S.T. Expression and cellular localization of ribonucleotide reductase small subunit M2 protein in hydroxyurea-resistant Leishmania mexicana amazonensis Mol. Biochem. Parasitol. 102: 263-271, 1999. 3. Chiang, S.C., Ali, V., Haung, A.L., Chu K.U., and Lee, S.T. Molecular, cellular and functional characterizations of a novel ICAM-like molecule of the Ig-superfamily from L. m. amazonensis. Mol. Biochem. Parasitol. 112: 263-275, 2001. 4. Chia, S.C., Leung, P.S.C., Liao, C.P., Huang, J.H. and Lee, S.T. Fragment of Japanese encephalitis virus envelope protein produced in Escherichia coli protects mice from virus challenge. Microbial Pathogenesis 31(1): 9-19, 2001. 5. Chang, Y.H., Lee, S.T. and Lin, W.W. Effects of cannabionoids on LPS-stimulated inflammatory mediator release from macrophages: involvement of Eicosanoids. J. Cell. Biochem. 81: 715-723, 2001. 6. Chiang, S.C., Chang, S.C. and Lee, S.T. ICAM-L gene is conserved only in Leishmania species in the family of kinetoplastida. Mol. Biochem. Parasitol. 124: 47-50, 2002. 7. Hsu, M.J., Lee, S.S., Lee, S.T. and Lin, W.W. Signaling mechanisms of enhanced neutrophil phagocytosis and chemotaxis by the polysaccharide purified from Ganoderma lucidum. Br. J. Pharmacol. 139(2): 289-98, 2003. 8. Chen, C.W., Lee, S.T., Wu, W.T., Fu W.M., Ho, F.M. and Lin, W.W. Signal transduction for inhibition of inducible nitric oxide synthase and cyclooxygenase-2 induction by capsaicin and related analogs in macrophages. Br. J. Pharmacol. 140: 1077-1087, 2003. 9. Wu, H.W., Chen, C.T., Lin, Y.L. and Lee, S.T. Subfragments of the envelope gene are highly protective against the Japanese encephalitis virus lethal infection in DNA priming/protein boosting immunization strategies. Vaccine, 22: 793-800, 2004. 28
  29. 29. Name in Chinese:林天南 Name in English:Lin, Teng-Nan Education:University of Missouri-Columbia Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3396, 886-2-2789-9141 Fax:886-2-2785-8847 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/tnlin_c.html E-mail:bmlth@ibms.sinica.edu.tw Fields of Specialty:Cerebral Ischemia , Angiogenesis ,Neurochemistry Research Description: Brain injury as a result of cerebral vascular disease (stroke) is a major health problem in Taiwan. Unfortunately, no treatment to limit brain damage is yet available. The need for intervention is great, both because of the seriousness of the disorder and its prevalence. The ultimate goal for us is to unravel the cellular and molecular mechanism of neuronal injury and/or recovery following ischemia-reperfusion. Both in vivo “focal cerebral ischemia model (MCAO)” and in vitro “primary neuronal and glial cultures” are using in our laboratory to explore these questions. Both pharmacological and genetic approaches are using to facilitate our goal. Research Interest: 1. Mechanism of Angiogenesis 2. Gene regulation of growth factors and their receptor 3. Cellular and molecular mechanism of neuronal injury and recovery 4. Gene transfer in CNS Selected Recent Publication: 29
  30. 30. 1. Lin T-N, Wang PY, Chi SI, Kuo JS (1998) Differential regulation of ciliary neurotrophic factor (CNTF) and CNTF receptor α(CNTFRα) expression following focal cerebral ischemia. Mol Brain Res 55:71-80. 2. Cheung WM, Wang CK, Kuo JS, Lin T-N (1999) Changes in the level of glial fibrillary acidic protein (GFAP) after mild and severe focal cerebral ischemia. Chinese J Physiology 42(4):227-235. 3. Lin T-N, Wang CK, Cheung WM, Hsu CY (2000) Induction of angiopoietin and tie receptor mRNA expression following cerebral ischemia-reperfusion. J. Cereb. Blood Flow Metab. 20:387-395. 4. Cheung WM, Chen SF, Nian GM, Lin T-N (2000) Induction of angiogenesis related genes in the contralateral cortex with a rat three-vessel occlusion model. Chinese J Physiology 43(3):119-124. 5. Chi SI, Wang CK, Chen JJ, Chau LY, Lin T-N (2000) Differential regulation of H- and L-ferritin mRNA subunits, ferritin protein and iron following focal cerebral ischemia- reperfusion. Neuroscience 100(3):475-484. 6. Shih CL, Chi SI, Chiu TH, Sun GY, Lin T-N (2001) Ethanol Effects on Nitric Oxide Production in Cerebral Pial Cultures. Alcoholism: Clin. Exp. Res. 25(4):612-618. 7. Lin T-N, Nian GM, Chen SF, Cheung WM, Chang C, Lin WC, Hsu CY (2001) Induction of Tie-1 and Tie-2 protein expression after cerebral ischemia-reperfusion. J. Cereb. Blood Flow Metab. 21(6):690-701. 8. Lin H, Lin T-N, Cheung WM, Nian GM, Tseng PH, Chen SF, Chen JJ, Shyue SK, Liou JY, Wu CW, Wu KK (2002) Cyclooxygenase-1 (COX-1) and Bicistronic COX- 1/Prostacyclin synthase gene transfer protect against ischemic cerebral infarction. Circulation 105:1962-1969 (r67-r74). 9. Lin T-N, Sun SW, Cheung WM, Li F, Chang C (2002) Dynamic changes in cerebral blood flow and angiogenesis after transient focal cerebral ischemia in rats: evaluation with serial MRI. Stroke 33:2985-2991. 10.Lin T-N, Kim GM, Chen JJ, Cheung WM, He YY, Hsu CY (2003) Differential regulation of TSP-1 and TSP-2 following focal cerebral ischemia-reperfusion. Stroke 34:177-186. 30
  31. 31. Name in Chinese:林文昌 Name in English:Lin, Wen-Chang Education:Case Western Reserve University Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3967, 886-2-2789-9148 Fax:886-2-2785-8594 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ wclin_c.html E-mail:wenlin@ibms.sinica.edu.tw Fields of Specialty:Bioinformatics, Tumor Biology, Cancer Metastasis Research Description: The long-term research goal of our laboratory is to utilize bioinformatic tools/databases in elucidating molecular and cellular aspects of tumor progression and host-tumor immune responses. Our research efforts are intended to improve treatment strategies of human cancer patients. Current major projects involve: 1. Examination of protein tyrosine-kinase and tyrosine-phosphatase expression profiles in human gastric cancer tissues. By using degenerated PCR primers according to the consensus catalytic domain motifs, we could amplify kinase/phosphatase molecules from cancer tissues. We have identified more than 50 different protein kinases as well as 20 different new protein kinase genes. We have demonstrated that expression of tie-1 and mkk4 kinases correlates with prognostic outcomes of gastric cancer patients. RAGE based bioinformatic tools are now in development to improve their applications in clinical studies. Bioinformatic is emerging as a new research field and becoming an important research tool. We have created a novel comparative-gene-identification (CGI) approach by applying 31
  32. 32. comparative proteomics in human dbEST data-mining efforts. With the CGI tool and human dbEST, we have discovered over 500,000 cSNP and a new wobble splicing mechanism in human gene transcripts. Our present goal is to integrate protein functional motif discovery and bioinformatic databases by building bioinformatic data-mining tools. Selected Recent Publication: 1. Hsiao-Wei Kao, Huan-Chen Chen , Hsing-Jien Kung, and Wen-chang Lin. 2003. Tyrosine-Kinase Expression Profiles in Human Gastric Cancer Cell Lines and Their Modulations with Retinoic Acids. British Journal of Cancer. 88: 1058-1064. 2. Chew-Wun Wu, Anna F.-Y. Li, Chin-Wen Chi, Cheng-Jien Huang, Chen Lung Huang, Wing-Yiu Liu, and Wen-chang Lin. 2003. Arg Tyrosine Kinase Expression in Human Gastric Adenocarcinoma is Associated with Vessel Invasion. Anticancer Res. 23: 205- 210. 3. Trees-Juen Chuang, Wen-Chang Lin, Hurng-Chun Lee, Chi-Wei Wang, Keh-Lin Hsiao, Zi-Hao Wang, Danny Shieh, Simon C. Lin, and Lan-Yang Ch'ang. 2003. A Complexity Reduction Algorithm for Analysis and Annotation of Large Genomic Sequences. Genome Research. 13: 313-322. 4. Wen-chang Lin. 2002. Protein Tyrosine Kinase and Phosphatase Expression Profiling in Human Cancers. In Methods in Molecular Medicine, Vol. 218: Cancer Cell Signaling: Methods and Protocols (David M. Terrian, ed.), Humana Press, Inc., Totowa, N.J. pp. 113-125. 5. Chew-Wun Wu, Anna F.-Y. Li, Chin-Wen Chi, Chun-Hung Lai, Chen Lung Huang, Su- Shun Lo, Wing-Yiu Liu, Wen-chang Lin. 2002. Clinical Significance of Axl Kinase Family in Gastric Cancer. Anticancer Res. 22: 1071-1078. 6. Chew-Wun Wu, Chin-Wen Chi, and Wen-chang Lin. 2002. Gastric Cancer: Prognostic and Diagnostic Advances. Expert Reviews in Molecular Medicine. 21 March, " http://www-ermm.cbcu.cam.ac.uk/02004337h.htm ". 7. Chun-Hung Lai, Jian-Yuan Chiu, and Wen-chang Lin. 2001. Identification of the Human crooked neck gene by Comparative Gene Identification. Biochimica et Biophysica Acta. 1517: 449-454. 8. Wen-chang Lin, Hsiao-Wei Kao, Daniel Robbinson, Hsing-Jien Kung, Chew-Wun Wu, and Hua-Chien Chen. 2000. Tyrosine Kinases and Gastric Cancer. Oncogene. 19: 5680- 32
  33. 33. 5689. 9. Chun-Huang Lai, Chang-Yuan Chou, Lan-Yang Ch'ang, Chung-Shyan Liu, Wen-chang Lin. 2000. Identification of Novel Human Genes Evolutionarily Conserved in C. elegans by Comparative Proteomics. Genome Res. 10: 703-713. 33
  34. 34. Name in Chinese:潘文涵 Name in English:Pan, Wen-Harn Education:Cornell University Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3042, 886-2-2789-9121 Fax:886-2-2782-3047 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/whpan_c.html E-mail:pan@ibms.sinica.edu.tw Fields of Specialty: Cardiovascular, Nutrition, Genetic Epidemiology Research Description: Our research mainly focuses on mRNA processing and transport in eukaryotic cells. The splicing of precursor mRNA is a key step of gene expression. In higher eukaryotes, alternative splicing of pre-mRNAs greatly increases the complexity of the genome8 . We have been interested in the molecular mechanisms by which alternative splicing is controlled. Serine/arginine-rich splicing factors (SR proteins) play important roles in both constitutive and regulated splicing. Dynamic localization of splicing regulatory factors provides a means by which splicing can be regulated. We therefore investigate the nucleocytoplasmic transport of SR proteins. We have identified an importin- beta family member, termed transportin-SR, and found that it is responsible for nuclear import of phosphorylated SR proteins3, 4 . We have also examined the roles of SR proteins in post-splicing mRNA maturation events9 . We are interested in how cellular signaling controls phosphorylation of SR proteins. We recently found that an SR protein becomes hyperphosphorylated upon inhibition of mRNA synthesis and that this SR protein is destabilized when hyperphosphorylated6 . In addition, we 34
  35. 35. identified a novel splicing regulatory protein, RBM4, that antagonizes the activity of SR proteins in splice site and exon selection5 . We also explore the molecular mechanisms of how transcription factors control splicing regulation2 and orchestrate the assembly of the spliceosome10 . RNA export is also a key step of gene expression. We recently found that SR-like protein Pnn/DRS becomes associated with the spliced mature mRNA during the splicing process. Our study indicates that Pnn functions as a platform for the assembly of splicing and/or export complexes in the nucleus7. At present, we continue to study whether phosphorylation of export factors has any effect on mRNA export. Selected Recent Publication: 1. Chang, H.Y., Suchindran, C.M. and Pan, W.H. Using the overdispersed exponential family to estimate the distribution of usual daily intakes of people aged between 18 and 28 in Taiwan. Statistics in Medicine 20(15): 2337-2350, 2001. 2. Chang, H.Y., Pan, W.H., Yeh, W.T. and Tsai, K.S. Hyperuricemia and gout in Taiwan: results from the Nutritional and Health Survey in Taiwan (NAHSIT: 1993-96). Journal of Rheumatology 28(7): 1640-1646, 2001. 3. Pan, W.H., Chang, H.Y., Yeh, W.T., Hsiao, S.Y. and Hung, Y.T. Prevalence, awareness, treatment and control of hypertension in Taiwan: results of nutrition and health survey in Taiwan (NAHSIT) 1993-1996. Journal Human Hypertension 15(11): 793-798, 2001. 4. Yeh, C.J., Pan, W.H., Jong, Y.S., Kuo, Y.Y. and Lo, C.H. Incidence and predictors of isolated systolic hypertension and isolated diastolic hypertension in Taiwan. Journal Formos Med Assoc. 100(10): 668-75, 2001. 5. Wu, S.Y., Fann, C.S.J., Chen, J.W., Jou, Y.S. and Pan, W.H. Association between markers in chromosomal region 17q23 and young-onset hypertension: A TDT study. Journal of Medical Genetics 39: 42-44, 2002. 6. Pan W.H., Yeh W.T., Chang H.Y., Hwu C.M., Ho L.T.. Prevalence and awareness of diabetes and mean fasting glucose by age, sex, and region: results from the Nutrition and Health Survey in Taiwan, 1993-1996. Diabet Med. 20(3):182-5, 2003. 7. Kang M.J., Lin Y.C., Yeh W.H., Pan W.H. Vitamin E status and its dietary determinants in Taiwanese: Results of the Nutrition and Health Survey in Taiwan 1993-1996. Eur J Nutr. 43(2): 86-92, 2004. 8. Pan W.H., Flegal K.M., Chang H.Y., Yeh W.T., Yeh C.J., Lee W.C. Body mass index 35
  36. 36. and obesity-related metabolic disorders in Taiwanese and US whites and blacks: implications for definitions of overweight and obesity for Asians. Am. J. of Clinical Nutrition 79: 31-39, 2004. 36
  37. 37. Name in Chinese:羅傅倫 Name in English:Roffler, Steve R. Education: University of California, Berkeley Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3079 886-2-2789-9152 Fax:886-2-2782-9142 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/roffler_c.html E-mail:sroff@ibms.sinica.edu.tw Fields of Specialty:Monoclonal Antibodies, Prodrugs, Surface Expression, Directed Molecular Evolution Research Description: We have synthesized glucuronide prodrugs that can be preferentially activated at tumor cells by antibody-enzyme conjugates (immunoenzymes). Current studies are focused on improving the utility of recombinant immunoenzymes by directed molecular evolution and translation of prodrug therapy to the clinic. We are also investigating the efficacy and mode of action of a new glucuronide prodrug of 9-aminocamptothecin that displays good antitumor activity without immunoenzyme pretargeting. Another area of interest is the development of novel gene-therapy strategies based on the expression of chimeric proteins on the surface of mammalian cells. We are focusing on the expression of enzymes for prodrug activation and single-chain antibodies for specific regulation of lymphocytes. We are interested in understanding how different domains of chimeric proteins affect their transport and retention on the cell surface. We have also developed monoclonal antibodies that identify proteins that are involved in the 37
  38. 38. migration, adhesion and invasion of lung adenocarcinoma cells as well as in the regulation of endothelial cell angiogenesis. Current studies are focused on investigation of protein-protein interactions and signal transduction pathways involved in cancer cell metastasis and angiogenesis. Selected Recent Publication: 1. NM Tsai, TL Cheng and SR Roffler. Sensitive quantitation of poly(ethylene glycol)- modified proteins. Biotechniques 30: 396-402, 2001. 2. BM Chen, TL Cheng, SC Tzou and SR Roffler. Potentiation of antitumor immunity by antibody-directed enzyme prodrug therapy. Int. J. Cancer, 94: 850-858, 2001. 3. JW Chen, K Peck, TM Hong, SC Yang, YP Sher, JY Shih, R Wu, JL Cheng, SR Roffler, CW Wu and PC Yang. Global Analysis of Gene Expression in Invasion by a Lung Cancer Model. Cancer Res., 61: 5223-5230, 2001. 4. KW Liao, WC Chou, YC Lo and SR Roffler. Design of transgenes for efficient expression of active chimeric proteins on mammalian cells. Biotechnol Bioeng, 73:313- 323, 2001. 5. ZM Prijovich, BM Chen, YL Leu, JW Chern and SR Roffler. Antitumor activity and toxicity of the new glucuronide prodrug 9-aminocamptothecin glucuronide (9ACG) in mice. Br. J. Cancer, 86: 1634-1638, 2002. 6. KM Bernt, DS Steinwaerder, S Ni, ZY Li, SR Roffler and A Lieber. Enzyme-activated prodrug therapy enhances tumor-specific replication of adenovirus vectors. Cancer Res., 62: 6089-98, 2002. 7. YR Kao, JY Shih, WC Wen, YP Ko, BM Chen, YL Chan, YW Chu, PC Yang, CW Wu and SR Roffler. Tumor-associated antigen L6 (TAL6) and the invasion of human lung cancer cells. Clin. Cancer Res., 9: 2807-2816, 2003. 8. KW Liao, BM Chen, TB Liu, SC Tzo, YM Lin, KF Lin, CI Su and SR Roffler. Stable expression of chimeric anti-CD3 receptors on mammalian cells for stimulation of anti- tumor immunity. Cancer Gene Therapy. 10: 779-790, 2003. 9. CH Lo, SC Lee, PY Wu, WY Pan, J Su, CW Cheng, SR Roffler, BL Chiang, CN Lee, CW Wu and MH Tao. Antitumor and antimetastatic activity of IL-23. J. Immunol. 171: 600-607, 2003. 10.ZM Prijovich, YL Leu and SR Roffler. Stability of the new prodrug 9- aminocamptothecin glucuronide (9ACG) in the presence of human serum albumin. 38
  39. 39. Biochem. Pharmacol., 66: 1181-1187, 2003. 39
  40. 40. Name in Chinese:謝如姬 Name in English:Shieh, Ru-Chi Education:University of Rochester Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3914, 886-2-2789-9024 Fax:886-2-2782-9143 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ruchi_c.html E-mail:ruchi@ibms.sinica.edu.tw Fields of Specialty:Electrophysiology, Biophysics, Fluorescence Research Description: Inward rectifier K+ channels (Kir) are important in maintaining stable resting membrane potentials and controlling excitability of many cells. These channels are also involved in other physiological processes such as vascular tone, heart rate, renal salt flow, and insulin release. The focus of our laboratory is on the ion permeating and gating processes in Kir2.1 channels. Recently, we have combined electrophysiology, site-directed mutangensis, and chemical modification to probe the conformational changes in Kir2.1 channels during membrane voltage-induced inactivation. Using this combination of techniques, we are currently studying the ion-ion interaction involved in ion permeation through the Kir2.1 channel. These experiments may shed light on the voltage-dependent gating processes of Kir2.1 channels and provide further insights into the interaction of permeant ions and blockers with the Kir2.1 channels. 40
  41. 41. Selected Recent Publication: 1. R-C Shieh. Mechanisms underlying the time-dependent decay of inward currents through cloned Kir2.1 channels expressed in Xenopus oocytes. J Physiol (Lond), 526.2:241-252, 2000. 2. R-C Shieh and Y-L Lee. Ammonium ions induce inactivation of Kir2.1 channels expressed in Xenopus oocytes. J Physiol (Lond), 535.2:359-370, 2001. 3. Wang, I., Wu, S.H., Chang, H.K., Shieh, R-C, Yu, H.M. and Chen, C. Solution structure of a K+ -channel blocker from the scorpion toxin of Tityus cambridgei. Protein Science 11: 390-400, 2002. 4. H-KChang and R-C Shieh. Conformational Changes in Kir2.1 Channels during NH4 + - Induced Inactivation. J Biol Chem 278 (2): 908-918, 2003. 5. H-K Chang, S-H Yeh, R-C Shieh. The effects of spermine on the accessibility of residues in the M2 segment of Kir2.1 channels expressed in Xenopus oocytes.J Physiol, 553(1):101-12, 2003. 41
  42. 42. Name in Chinese:謝小燕 Name in English:Shieh, Sheau-Yann Education:Baylor College of Medicine Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Assistant Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3916, 886-2-2789-9056 Fax:886-2-2782-9143 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ssy_c.html E-mail:sy88@ibms.sinica.edu.tw Fields of Specialty:Cancer Research, Molecular Biology, Biochemistry Research Description: The tumor suppressor protein p53 play an important role in maintaining genome stability. The significance is fully illustrated by its high frequency (over 50%) of deletion or mutation in tumors. Under normal condition, the cellular p53 protein is unstable and barely detectable. However, upon genotoxic stress such as ionizing radiation, UV, hypoxia, or even nutrient depletion, p53 is stabilized and activated, which then leads to either G1/G2 growth arrest or programmed cell death (apoptosis). Our main interest is to decipher the signal transduction pathways and the molecular mechanisms underlying p53 induction. DNA damage-induced p53 phosphorylation The possibility that phosphorylation may play a role in the signaling to p53 has been a subject of intense investigation. In fact, we and others have discovered that DNA damage induces p53 phosphorylation at multiple sites in the N-terminus and the C-terminus of the protein. However, the connection between these phosphorylation events and p53 induction remains to be established. We 42
  43. 43. have recently identified two cell cycle checkpoint kinases, hCHK1 and CHK2, as p53 kinases that phosphorylate DNA damage-inducible sites in vitro. The possibility that other cell cycle checkpoint players may also participate in the signal transduction process upstream of CHKs is now under investigation. We are also interested in identifying additional p53 kinases and their interacting proteins, as well as their effects on p53. Molecular mechanism underlying p53 stabilization Several proteins have been shown to regulate the half-life of p53 either directly or indirectly. One of them, the oncoprotein MDM2, binds the N-terminus of p53, and as a result, inhibits transcription activation by p53 and promotes p53 degredation through ubiquitin / proteasome pathway. Although p53 N-terminal phosphorylation can modulate MDM2-p53 interaction, some stress-related stabilization of p53 does not appear to involve phosphorylation. Other lines of evidence also suggest that different genotoxic agents may signal to p53 through different pathways. We are interested in locating the responsible p53 domain(s) that can mediate these stabilizing effects, as well as potential proteins that interact with these domains. Selected Recent Publication: 1. Tibbetts, R.S., Brumbaugh, K.M., Williams, J.M., Sarkaria, J.N., Cliby, W.A., Shieh, S.Y., Taya, Y., Prives, C. and Abraham, R.T. A role for ATR in the DNA damage- induced phosphorylation of p53. Genes & Dev. 13: 152-157, 1999. 2. Shieh, S.Y., Taya, Y. and Prives, C. DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, serine 20, requires tetramerization. EMBO J. 18: 1815-1823, 1999. 3. Shieh, S.Y., Ahn, J., Tamai, K., Taya, Y. and Prives, C. The human homologues of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage inducible sites. Genes & Dev. 14: 289-300[user1], 2000. 4. Gottifredi, V., Shieh, S. -Y. and Prives, C. Regulation of p53 after different forms of stress and at different cell cycle stage. Cold Spring Harbor Symp. Quant. Biol. LXV: 483-487, 2000. 5. Gottifredi, V., Karni-Schmidt, O., Shieh, S.-Y. and Prives, C. p53 down-regulates CHK1 through p21 and the retinoblastoma protein. Mol. Cell. Biol. 21: 1066-1076, 2001. 6. Gottifredi, V., Shieh, S.Y., Taya, Y. and Prives, C. p53 accumulates but is functionally impaired when DNA synthesis is blocked. Proc. Natl. Acad. Sci. USA 98: 1036-1041, 43
  44. 44. 2001. 44
  45. 45. Name in Chinese:徐松錕 Name in English:Shyue, Song-Kun Education:Universityn of Texas-Houston Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Assistant Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3962, 886-2-2789-9153 Fax:886-2-2785-8847 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/skshyue_c.html E-mail:skshyue@ibms.sinica.edu.tw Fields of Specialty: Viral Vector Gene Transfer, Cardiovascular Diseases Research Description: We have been working with adenovirus (Ad) mediated gene transfer and therapy to study cardiovascular related diseases and molecular mechanism. Ad is one of the most efficient delivering vectors for in vivo and in vitro gene transfer. First and E2b deleted second generation Ad systems have been established in our laboratory. We have constructed many recombinant Ads related to antioxidants, vasoprotection and immune response. We are currently focusing on the following projects: 1. Modifying Ad delivery system by: 1) Cells and protocol modification to improve viral packaging and production efficiency to save time and cost. 2) To improve and develop 2nd and 3rd generation Ad in their construct and production for long term gene therapy. 2. Investigating the protection and therapeutic effects as well as their molecular mechanisms of vasoprotective molecules in cardiovascular diseases, including atherosclerosis and pulmonary hypertension. 3. Gene regulation and its mechanism of caveolin-1 in cancer cells. 45
  46. 46. 4. Using microarray and proteomic tools to study the constitutional types in Traditional Chinese Medicine, such as hot and cold, to unveil their related genes and proteins, and to investigate the molecular mechanism of Traditional Chinese Medicine. Selected Recent Publication: 1. Li, W. H., Boissinot, S., Tan, Y., Shyue, S.K. and Hewett-Emmett, D. Evolutionary genetics of primate color vision. Evolutionary Biology 32: 151-178, 2000. 2. Shyue, S.K., Tsai, M.J., Liou, J.Y., Willerson, J.T. and Wu, K.K. Selective augmentation of prostacyclin production by combined prostacyclin synthase and cyclooxygenase-1 gene transfer. Circulation 103:2090-2095, 2001. 3. Liou, J.Y., Deng, W.G., Gilroy, D.K., Shyue, S.K. and Wu, K.K. Colocalization and interaction of cyclooxygenase-2 with caveolin-1 in human fibroblasts. J. Biol. Chem. 276: 34975-82, 2001. 4. Juan, S.H., Lee, T.S., Tseng, K.W., Liou, J.Y., Shyue, S.K., Wu, K.K. and Chau, L.Y. Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apoE-deficient mice. Circulation 104: 1519-25, 2001. 5. Lin H, Lin TN, Cheung WM, Nian GM, Tseng PH, Chen SF, Chen JJ, Shyue SK, Liou JY, Wu CW, Wu KK. Cyclooxygenase-1 and bicistronic cyclooxygenase-1/prostacyclin synthase gene transfer protect against ischemic cerebral infarction. Circulation Apr 23;105(16):1962-9, 2002. 6. Yu, N, Chen, FC, Ota, S, Jorde, LB, Pamilo, P, Patthy, L, Ramsay, M, Jenkins, T, Shyue, SK, Li, WH. Larger genetic differences within africans than between africans and eurasians. Genetics 161(1):269-74, 2002. 7. Huang CL, Huang NK, Shyue SK, Chern Y. Hydrogen peroxide induces loss of dopamine transporter activity: a calcium-dependent oxidative mechanism. J Neurochem. 86(5):1247-59, 2003. 8. 游恆懿、徐松錕、陳光偉 以基因晶片分析經附子乾薑培養的腎細胞基因表達。中西 整合醫學雜誌 4(1):1-6, 2003. 9. Lin SJ, Shyue SK, Liu PL, Chen YH, Ku HH, Chen JW, Tam KB and Chen YL Adenovirus-mediated overexpression of catalase attenuates oxLDL-induced apoptosis in human aortic endothelial cells via AP-1 and C-Jun N-terminal kinase/extracellular signal-regulated kinase mitogen-activated protein kinase pathways. J. Mol. Cell. 46
  47. 47. Cardiol. 36(1):129-39, 2004. 47
  48. 48. Name in Chinese:唐堂 Name in English:Tang, Tang k.. Education:Yale University Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3901, 886-2-2789-9156 Fax:886-2-2782-9143 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ttang_c.html E-mail:tktang@ibms.sinica.edu.tw Fields of Specialty:Cell and Developmental Biology, Cell Mitosis and Germ Cell Development Research Description: A). Cell Cycle Control and Cancer Genetic Instability Genetic instability is a common characteristic of many human cancers. Although, little is known about the mechanisms that generate genetic abnormality, missegregation of chromosomes through the assembly of dysfunctional mitotic spindles may play essential roles. The centrosome functions as the major microtubule organizing center of the cells. During cell mitosis, the centrosome organizes the microtubule array of the mitotic spindle and thereby makes possible equal segregation of sister chromatids into two daughter cells. Many reports have shown that defects in centrosome function lead to aneuploid and genetic instability in cancer cells. We previously identified several centrosomal proteins including aurora-A, CPAP, protein 4.1 and NuMA. In this project, we propose to systematically and qualitatively analyze the protein composition of centrosome by proteomic approach, particularly focusing on the identification of novel centrosomal kinases and their substrates. Furthermore, we will examine the possible roles of these newly identified proteins involved in cell 48
  49. 49. mitosis and genomic instability. B). Gene Regulation and Germ Cell Development Spermatogenesis in mammals is a complex system that leads to the formation of male gametes. During spermatogenesis, male germ cells undergo major morphological and biochemical changes, which are regulated by the stage-specific transcriptional and translational activation of numerous genes and protein kinases. We previously identified a novel serine/threonine kinase, Aie1 (aurora-C) and its gene regulator Tzfp (testis zinc finger protein). Both Aie1 and Tzfp are expressed in testis and particularly in meiotic pachytene spermatocytes, suggesting a possible role of these two proteins involved in spermatogenesis. Recently, we demonstrate that Tzfp binds to the promoter region of Aie1 gene through its carboxyl zinc finger domain, which suggests that the expression of Aie1 gene may be regulated by Tzfp. We currently produced Tzfp knockout mice. The possible roles of these two proteins are currently under investigation. The results from these studies should explore the unrevealed signaling pathways and regulation in germ cell development in the future. Selected Recent Publication: 1. Hung, L-Y., Tang, C-J. C., Tang, T.K. (2000). P4.1R (135 kDa) interacts with a novel centrosomal protein (CPAP), which is associated with the -tubulin complex. Mol. Cell. Biol. 20, 7813-7825. 2. Tang, C-J.C., Chuang, C-K., Hu, H-M., and Tang, T.K. (2001) The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. J. Biol. Chem. 276, 19631-19639. 3. Chen, S-H., and Tang T.K. (2002) Mutational analysis of the phosphorylation sites of the Aie1(aurora-C) kinase in vitro. DNA Cell Biol. 21, 41-46. 4. Peng, B., Sutherland, K.D., Sum, E.Y.M., Olayioye, M., Wittlin, S., Tang, T.K., Lindeman, G.J., and Visvader, J.E. (2002) CPAP is novel Stat5-interacting cofactor that augments Stat5-mediated transcriptional activity. Mol. Endocrinol. 16, 2019-2033. 5. Hung, L-Y., Chang, C-W., and Tang, T. K. (2003) Methods and compositions for destabilizing microtubules. USA Patent-pending application 6. Tang, C-J. C., Hu, H-M, and Tang, T. K. (2004) NuMA (Nuclear Mitotic Apparatus Protein) expression and function in mouse oocyte and early embryo. J. Biomed. Sci. (in press). 7. Hung, L-Y., Chen, H-L., Chang, C-W., Li, B-R., and Tang, T. K. (2004) Identification of 49
  50. 50. a novel microtubule-destabilizing motif in CPAP that binds to tubulin heterodimers and inhibits microtubule assembly. Mol. Biol. Cell. (in press) 50
  51. 51. Name in Chinese:陶秘華 Name in English:Tao, Mi-Hua Education: Columbia University Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3078, 886-2-2789-9151 Fax:886-2-2782-9142 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/ tao_c.html E-mail:bmtao@ibms.sinica.edu.tw Fields of Specialty:Infectious Disease, Immunology, Vaccines, Tumor immunology, Hepatitis B virus immunology Research Description: The major interest of our laboratory is to develop novel immunotherapeutic methods for treating cancers and chronic hepatitis B virus infection. We focus on applying cytokines and immune costimulatory molecules to modulate immune responses for enhancing the therapeutic effects. The state of the art technologies, such as DNA vaccines, dendritic cell vaccines, in vivo electroporation, and engineered antibodies are used in these studies. Details of our current research projects can be found at the web site www.ibms.sinica.edu.tw/%7Ebmtao/. Following are brief summaries of some of our research activities: 1. Cancer Immunotherapy and Gene Therapy We have generated immunocytokines that can target cytokines to the tumor site to enhance their tumoricidal effects. Application of immunocytokines is one of the most promising approaches developed recently for cancer immunotherapy. Cytokines and other costimulatory molecules are 51
  52. 52. also applied to engineer tumor antigens to generate more potent cancer vaccines. 2.Therapeutic Vaccines for Treatment of Chronic Hepatitis B Virus Infection We have previously demonstrated that plasmid DNA encoding HBsAg induced humoral and cellular immune responses. We also demonstrated that the magnitude and nature of the immune responses induced by HBsAg DNA vaccine could be modulated by coexpression of cytokine plasmids. Based on these results, we are now developing therapeutic vaccines against chronic HBV infections using several novel approaches including DNA vaccines, dendritic-cell-based vaccines, and adenovirus producing cytokines/costimulatory molecules. A number of HBV transgenic mouse strains have been generated as animal models for HBV chronic infection. Selected Recent Publication: 1. Huang, T.H., Wu, P.Y., Lee, C.N., Huang, H.I., Hsieh, S.L., Kung, J. and Tao, M.H. Enhanced antitumor immunity by fusion of CTLA-4 to a self tumor antigen. Blood (Plenary paper) 96: 3663-3670, 2000. 2. Chen, H.W., Pan, C.H., Huang, H.W., Liau, M.Y., Chiang, J.R. and Tao, M.H.. Suppression of immune response and protective immunity to a Japanese encephalitis virus DNA vaccine by coadministration of an IL-12-expressing plasmid. J. Immunol. 166: 7419-7426, 2001. 3. Pan, C.H., Chen, H.W., Huang, H.W. and Tao, M.H.. Protective mechanisms induced by a Japanese encephalitis virus DNA vaccine: requirement for antibody but not CD8+ cytotoxic T cell responses. J. Virol. 75: 11457-11463, 2001 4. Lee, S.C., Wu, C.J., Wu, P.Y., Huang, Y.L., Wu, C.W. and Tao, M.H. Inhibition of estabhished subcutaneous and metastatic murine tumors by intramuscular electroporation of the Interleukin 12 gene. J. Biomed. Sci. 10: 73-86, 2003 5. Lo, C.H., Lee, S.C., Wu, P.Y., Pan, W.Y., Su, J., Cheng, C.W., Roffler, S.R., Chiang, B.L., Lee, C.N., Wu, C.W. and Tao, M.H. Antitumor and antimetastatic activity of Interleukin 23. J. Immunol. 171: 600-607, 2003 6. Wu, C.J., Huang, H.W. and Tao, M.H. Induction of cross-protection against two wild- type Taiwanese isolates of Japanese encephalitis virus using Beijing-1 strain DNA vaccine. Vaccine 21: 3938-3945, 2003 7. Huang, H.I., Wu, P.Y., Teo, C.Y., Chen, M.N., Chen, Y.C. and Tao, M.H. Idiotype-CD40 ligand fusion protein induces protective immunity against B-cell lymphoma. Int. J. 52
  53. 53. Cancer 108: 696-703, 2004. 53
  54. 54. Name in Chinese:譚婉玉 Name in English:Tarn, Woan-Yuh Education:National Tsing Hua University Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3052, 886-2-2789-9015 Fax:886-2-2782-9142 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/wutarn_c.html E-mail:wtarn@ibms.sinica.edu.tw Fields of Specialty:mRNA processing, Nucleocytoplasmic transport Research Description: Our research mainly focuses on mRNA processing and transport in eukaryotic cells. The splicing of precursor mRNA is a key step of gene expression. In higher eukaryotes, alternative splicing of pre-mRNAs greatly increases the complexity of the genome8 . We have been interested in the molecular mechanisms by which alternative splicing is controlled. Serine/arginine-rich splicing factors (SR proteins) play important roles in both constitutive and regulated splicing. Dynamic localization of splicing regulatory factors provides a means by which splicing can be regulated. We therefore investigate the nucleocytoplasmic transport of SR proteins. We have identified an importin- beta family member, termed transportin-SR, and found that it is responsible for nuclear import of phosphorylated SR proteins3, 4 . We have also examined the roles of SR proteins in post-splicing mRNA maturation events9 . We are interested in how cellular signaling controls phosphorylation of SR proteins. We recently found that an SR protein becomes hyperphosphorylated upon inhibition of mRNA synthesis and that this SR protein is destabilized when hyperphosphorylated6 . In addition, we identified a novel splicing regulatory protein, RBM4, that antagonizes the activity of SR proteins in 54
  55. 55. splice site and exon selection5 . We also explore the molecular mechanisms of how transcription factors control splicing regulation2 and orchestrate the assembly of the spliceosome10 . RNA export is also a key step of gene expression. We recently found that SR-like protein Pnn/DRS becomes associated with the spliced mature mRNA during the splicing process. Our study indicates that Pnn functions as a platform for the assembly of splicing and/or export complexes in the nucleus7. At present, we continue to study whether phosphorylation of export factors has any effect on mRNA export. Selected Recent Publication: 1. Tarn, W. Y. and Steitz, J. A. Pre-mRNA splicing: the discovery of a new spliceosome doubles the challenge. Trends Biochem. Sci. 22: 132-137, 1997. 2. Lai, M. C., Teh, B. H. and Tarn, W. Y. A human papillomavirus E2 transcriptional activator: the interactions with cellular splicing factors and potential function in pre- mRNA processing. J. Biol. Chem. 274: 11832-11841, 1999. 3. Lai, M. C., Lin, R. I., Huang, S. Y., Tsai, C. W. and Tarn, W. Y. A human importin-_ family protein, transportin-SR2, interacts with the phosphorylated RS domain of SR proteins. J. Biol. Chem. 275: 7950-7957, 2000. 4. Lai, M. C., Lin, R. I. and Tarn, W. Y. Transportin-SR2 mediates nuclear import of phosphorylated SR proteins. Proc. Natl. Acad. Sci. USA 98: 10154-10159, 2001. 5. Lai, M. C., Kuo, H. W., Chang, W. C. and Tarn, W. Y. A novel splicing regulator shares a nuclear import pathway with SR proteins. EMBO J. 22: 1359-1369, 2003. 6. Lai, M. C., Lin, R. I. and Tarn, W. Y. Differential Effects of Hyperphosphorylation on Splicing Factor SRp55. Biochem. J. 371: 937-945, 2003. 7. Li, C. Lin, R. I., Lai, M. C., Ouyang, P., and Tarn, W. Y. Nuclear Pnn/DRS protein binds to spliced mRNPs and participates in mRNA processing and export via the interaction with RNPS1. Mol. Cell. Biol. 23:7363-7376, 2003. 8. Lai, M. C. and Tarn, W. Y. Hypophosphorylated ASF/SF2 binds TAP and is present in mRNPs. J. Biol. Chem. (in press), 2004. 9. Li, C., and Tarn, W.-Y. Splicing. In: Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine. (ed) K. Ruckpaul and D. Ganten; Springer-Verlag. (in press), 2004 55
  56. 56. 10. Lin, K. T., Leu, R. M. and Tarn, W. Y. The WW domain-containing proteins interact with the early spliceosome and facilitate 3' splice site selection. (manuscript submitted), 2004. 56
  57. 57. Name in Chinese:王寧 Name in English:Wang, Danny Ling Education: University of Nevada Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3907, 886-2-2789-9132 Fax:886-2-2782-9143 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/lwang_c.html E-mail:lingwang@ibms.sinica.edu.tw Fields of Specialty:Vascular Biology, Gene Regulation ,Oxidative Stress Research Description: Vascular endothelial cells play an important role in maintaining vessel integrity. Oxidative stress to endothelial cells contributes to the pathogenesis of vascular diseases. Our studies suggest that changes of intracellular redox status may be the underlying mechanism that modulates signaling pathways and result in alteration of gene expression in endothelial cells under chemical or mechanical stimuli. Endothelial cells under hemodynamic flow protect themselves from cytokine-induced responses. These protective mechanisms are not clear. Protein tyrosine phosphatases may play important roles in suppressing signaling pathways. In addition, endothelial cells constantly release nitric oxide that plays as a negative regulator for endothelial responses. How nitric oxide affects signaling pathways and gene expression is not well defined. The consequence of interplay between reactive oxygen species and nitrogen species may determine the endothelial responses to various stimuli. Our research interests have been focusing on: 1. Signaling mechanisms and gene regulation in endothelial cells under oxidative stress. 57
  58. 58. 2. The molecular mechanisms of shear-induced protective effects in endothelial cells 3. The role of phosphatase(s) in endothelial cells under inflammatory condition. 4. The protective role of nitric oxide in endothelial cells 5.The interaction of endothelial cells with smooth muscle cells and leukocytes that contribute to vessel dysfunction. Selected Recent Publication: 1. Chiu, J.J., Wung, B.S., Hsieh, H.J., Lo, L.W. and Wang, D.L. Nitric oxide regulates shear stress-induced early growth response-1 expression via the extracellular signal-regulated kinase pathway in endothelial cells. Circ. Res. 85: 238-246, 1999. 2. Lo, L.W., Cheng, J.J., Chiu, J.J., Wung, B.S., Lu, Y.C. and Wang, D.L. Endothelial exposure to hypoxia induces Egr-1 expression involving PKC a-mediated Ras/Raf/ERK1/2 pathway. J. Cell. Physiol., 188: 304-312, 2001. 3. Chang, Y.L., Shen, J.J., Wung, B.S., Cheng, J.J. and Wang, D.L. Chinese herbal remedy wogonin inhibits monocyte chemotactic protein-1 gene expression in human endothelial cells. Mol. Pharmocol. 60: 507-513, 2001. 4. Cheng, J.J., Wung, B.S., Chao, Y.J. and Wang, D.L.Sequential activation of protein kinase C-a and -e is required for cyclic strain-induced ERK1/2 activity in endothelial cells. J. Biol. Chem. 276(33): 31368-31375, 2001. 5. Wung, B.S. and Wang, D. L.NO modulates monocyte chemotactic protein-1 expression in endothelial cells under cyclic strain. Arterioscler. Thromb. Vasc. Biol. 21: 1941-47, 2001. 6. Cheng Jing-Jy, Chao Y-J and Wang D.L. “Cyclic Strain Activates Redox-Sensitive Proline- Rich Tyrosine Kinase (PYK2) in Endothelial Cells” J. Biol. Chem. 277 (50): 48152-57, 2002. 7. Ni C-W., Wang D.L., Lien S-C., Cheng J-J., Chao Y-J, And Hsieh H-J. “Activation of PKC-ε and ERK1/2 participates in shear-induced endothelial MCP-1 expression that is repressed by nitric oxide” J. Cell. Physiol. 195:428-434 (2003). 8. Ni C-W., Hsieh H-J, Chao Y-J and Wang D.L. “Shear Flow Attenuates Serun-Induced STAT3 Activation in Endothelial Cells.” J. Biol. Chem. 278 (22):19702-08, 2003. 9. Chen S. H., Wang D. L. “Nitric oxide inhibiting MMP–2 Expression is mediated via the induction of activating transcription factor (ATF3) in endothelial cells.” Mol. Pharmacology 65(5) (in press). 2004. 58
  59. 59. Name in Chinese:顏裕庭 Name in English:Yan, Yu-Ting Education: University of Medicine and Dentistry of New Jersey Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Assistant Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3914 886-2-2789-9061 Fax:886-2-2785-8847 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/yyt_c.html E-mail:yyan@ibms.sinica.edu.tw Fields of Specialty:Molecular Genetics, Developmental Biology Research Description: The left-right (L-R) asymmetry of visceral organs is known to depend on left- and right-side specific cascades of gene expression during gastrulation and early post-gastrulation stages of embryogenesis. Failure to establish correct pattern of L-R axis results in heterotaxy, either expressed as randomization (situs ambiguous) or complete reversal (situs inversus) of normal organ position. In mammals, the correct pattern of the L-R axis is very critical for viability, since defects in the L-R laterality in newborn children are often associated with severe complex congenital cardiovascular defects, such as atrial or ventricular septal defect (ASD or VSD) and transposition of great arteries (TAG). The major research interest of our laboratory is to elucidate the molecular and biochemical mechanism of specification of L-R axis patterning of mammals, and to understand how L-R positional information is interpreted at a tissue-specific level during organogenesis. We utilize mouse as an experimental system, taking advantage of the assets that the system has to offer, including its small 59
  60. 60. size, genetics, transgenics and reverse genetics or gene targeting. Targeted disruption of mouse Cryptic results in L-R laterality defects including randomization of abdominal situs, hyposplenia, and pulmonary right isomerism, as well as randomized embryo turning and cardiac looping. Currently, the work of my laboratory is focused on the following two projects: (1) investigation of L-R axis lateral defects on the development cardiac and vascular system using Cryptic mutant mouse as a study model, (2) identification and characterization of new candidate genes involved in determination of L-R axis. Selected Recent Publication: 1. Iratni, R., Yan, Y.-T., Chen, C., Ding, J., Zhang, Y., Price, S. M., Reinberg, D., and Shen, M. M. (2002). Inhibition of excess Nodal signaling during mouse gastrulation by the transcriptional corepressor DRAP1. Science 298, 1996-1999. 2. Yan, Y.-T., Liu, J.-J., Luo, Y., E, C., Haltiwanger, R. S., Abate-Shen, C., and Shen, M. M. (2002). Dual roles of Cripto as a ligand and co-receptor in the Nodal signaling pathway. Mol. Cell. Biol. 22, 4439-4449. 3. Yan, Y.-T., Stein, S. M., Ding, J., Shen, M. M., and Abate-Shen, C. (2000). A novel PF/PN motif inhibits nuclear localization and DNA binding activity of the ESX1 homeoprotein. Mol. Cell. Biol. 20, 661-671. 4. Yan, Y.-T., Gritsman, K., Ding, J., Burdine, R. D., Corrales, J. D., Price, S. M., Talbot, W. S., Schier, A. F., and Shen, M. M. (1999). Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation. Genes Dev. 13, 2527-2537. 60
  61. 61. Name in Chinese:楊瑞彬 Name in English:Yang, Ruey Bing Ray Education:University of Texas Sounthwestern Medical Center at Dallas Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Associate Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3943, 886-2-2789-9063 Fax:886-2-2785-8847 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/rbyang_c.html E-mail:rbyang@ibms.sinica.edu.tw Fields of Specialty:Receptor biology, Signal Transduction , Vascular Biology, Genomics Research Description: Current research interest of our laboratory is to unravel the biological functions of several novel cell-surface proteins. We have previously utilized a combination of high throughput sequencing and genome-wide microarray profiling analyses to identify novel cell-surface proteins expressed in human umbilical vein endothelial cells. One gene family identified by this approach encodes potential secreted proteins harboring multiple copies of epidermal growth factor-like domain and one CUB domain at the carboxyl terminus. Recently, we have identified one additional member with an osteoblast-enriched expression profile that is completely distinct from the endothelial expression of two previously identified family members. Recent immunohistochemical staining and molecular genetic studies suggested that members of this gene family may play important roles in the pathogenesis of cardiovascular or bone diseases. Another gene identified by this approach encodes a novel type I transmembrane receptor expressed in a testis-specific fashion. In the near future, we will apply molecular and biochemical 61
  62. 62. methodologies as well as gene targeting approach to further evaluate their functions in the cardiovascular, bone and reproductive biology. Selected Recent Publication: 1. Brightbill, H.D., Libraty, D.H., Krutzik, S.R., Yang, R.-B., Belisle, J.T., Maitlan, M., Norgard, M.V., Plevy, S.E., Smale, S.T., Brennan, P.J., Bloom, B.R., Godowski, P.J., and Modlin, R.L. Microbial lipoproteins trigger host defense mechanisms via Toll-like receptors. Science 285: 732-736, 1999. 2. Yang, R.-B., Mark, M.R., Gurney, A.L., and Godowski, P.J. Signaling events induced by lipopolysaccharide-activated Toll-like receptor-2. J. Immunol. 163: 639-643, 1999. 3. Yang, R.-B., Robinson, S.W., Birch, D.G., and Garbers, D.L. Disruption of a retinal guanylyl cyclase gene leads to cone-specific dystrophy and paradoxical rod behavior. J. Neurosci. 19: 5889-5897, 1999. 4. Aliprants, A.O., Yang, R.-B., Weiss, D.S., Godowski, P.J., and Zychlinsky, A. The apoptotic signaling pathway activated by Toll-like receptor 2. EMBO J. 19: 3325-3336, 2000. 5. Hollopeter, G., Jantzen, H.-M., Vincent, D., Li, G., England, L., Ramakrishnan, V., Yang, R.-B., Nurden, P., Nurden, A., Julius, D., and Conley, P.B. Molecular identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 409: 202-207, 2001. 6. Yang, R.-B., Ng, C.K.D., Wasserman, S.M., Komuves, L.G., Tomlinson, J.E., and Topper, J.N. Identification of a family of cell-surface proteins expressed in human vascular endothelium. J. Biol. Chem. 277: 46364-46373, 2002. 7. Wasserman, S.M., Mehraban, F., Komuves, L.G., Yang, R.-B., Tomlinson, J.E., Spriggs, F. and Topper, J.N. Gene Expression profile of human endothelial cells exposed to sustained fluid shear stress. Physiol. Genomics 12: 13-23, 2002. 8. Yang, R.-B.*, Ng, C.K.D., Wasserman, S.M., Komuves, L.G., Gerritsen, M.E., and Topper, J.N. A novel IL-17 receptor-like protein identified in human umbilical vein endothelial cells antagonizes basic fibroblast growth factor-induced signaling. J. Biol. Chem. 278: 33232-33238, 2003. (* Corresponding author) 9. Kuhn, M., Ng, C.K.D., Su, Y.-H., Kilic, A., Mitko, D., Bien-Ly, N., Komuves, L.G., Yang, R.-B. Identification of a novel receptor guanylyl cyclase selectively expressed in 62
  63. 63. mouse testis. Biochem. J. 379: 385-393, 2004. 63
  64. 64. Name in Chinese:嚴仲陽 Name in English:Yen, Jeffrey J.Y. Education: Baylor College of Medicine Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3077 886-2-2789-9017 Fax:886-2-2782-9142 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/yen_c.html E-mail:bmjyen@ibms.sinica.edu.tw Fields of Specialty: Molecular & Cell Biology, Hematopoiesis, Apoptosis Regulation Research Description: The long term interest of my laboratory has been on the growth and death regulation of hematopoietic cell lineages due to the underlying mechanism may shed lights on many human detrimental diseases, including leukemia, immunodeficiencies, allergic disorders, asthma, and autoimmunities. In the past ten years, we have applied standard molecular and cellular biology techniques to pursue our goals in terms of involvement of specific genes in the death regulation of hematopoietic cells. We continued to work on the molecular mechanism triggering the programmed cell death when cytokine was depleted. A novel cytokine receptor associated signaling molecule as well as a novel cytokine deprivation-induced early gene are identified. They both were found to be strongly apoptogenic to hematopoietic cells, suggesting the likelihood of the involvement of these novel molecules in this process. On the other hand, we discovered the involvement of the erythroid transcriptional factor GATA-1 in transducing anti-apoptotic acitivity of interleukin 3 in cytokine dependent hematopoietic cell line. Intriguingly, there is a strong correlation between tissue expression 64
  65. 65. profile of GATA family members and their target anti-apoptotic gene E4BP4, suggesting the survival effect of GATA family proteins may play an important role in multiple organ development. In the new millennium, we also included molecular genetic and functional genomic approaches to tackle the regulatory mechanism of apoptosis control. We are currently actively participating in the genome-wide phenotype-driven ENU-mutagenized mice screening program for the hematopoietic deficiency phenotype. Once the mutation is confirmed and chromosomal location is mapped, high- resolution genetic mapping and molecular cloning of the defected gene will be pursued using various genomic research tools, such as SNP discovery, bioinformatics and transgenic rescue. We are at present working on a mutant mouse line with segmental progeroid symdrome and another line with lymphocytopenia and combined immune deficiency. Our preliminary study suggested that both mutations affect the survival of either stem cell population or lymphoid cell lineages. Selected Recent Publication: 1. Huang, H.M., Li, J.C., Hsieh, Y.C., Yang-Yen, H.F. and Yen, J.J.Y. Optimal proliferation of a hematopoietic progenitor cell line requires either costimulation with stem cell factor or increase of receptor expression that can be replaced by overexpression of Bcl- 2. Blood 93: 2569-2577, 1999. 2. Lee, S.F., Huang, H.M., Chao, J.R., Lin, S., Yang-Yen, H.F. and Yen, J.J.Y. Cytokine receptor common a chain as a potential activator of cytokine withdrawal-induced apoptosis. Mol. Cell. Biol. 19: 7399-7409, 1999. 3. Huang, H.M., Huang, C.J. and Yen, J.J.Y. Mcl-1 is a common target of stem cell factor and interleukin 5 for apoptosis prevention activity via MEK/MAPK and PI-3K/Akt pathways. Blood 96: 1764-1771, 2000. 4. Chen, W., Yu, Y.L., Lee, S.F., Chiang, Y.J., Chao, J.R., Huang, J.H., Chiong, J.H., Huang, C.J., Lai, M.Z., Yang-Yen, H.F. and Yen, J.J.Y. CREB is one component of the binding complex of the Ces-2/E2A-HLF binding element and is an integral part of the IL-3 survival signal. Mol. Cell. Biol. 21: 4636-4646, 2001. 5. Yu, Y.L., Chiang, Y.J., and Yen, J.J.Y. GATA factors are essential for transcription of the survival gene E4BP4 and the viability response of interleukin-3 in Ba/F3 hematopoietic cells. J. Biol. Chem.277:27144-27153, 2002. 65
  66. 66. Name in Chinese:蕭百忍 Name in English:Yen, Pauline, H. Education: University of California, Berkeley Affiliation:Institute of Biomedical Sciences, Academia Sinica, Taipei Title:Research Fellow, Institute of Biomedical Sciences, Academia Sinica Tel:886-2-2652-3912 886-2-2789-9055 Fax:886-2-2782-9224 My Personal Homepage:http://www.ibms.sinica.edu.tw/html/PI/pyen_c.html E-mail:pyen@ibms.sinica.edu.tw Fields of Specialty:Human Genetics Research Description: The mammalian sex chromosomes play important roles in spermatogenesis. More than half of the genes on the human Y chromosome and numerous genes on the X chromosome are expressed exclusively in the testis. Microdeletion of the Y chromosome and the presence of an extra X chromosome in the Klinefelter syndrome patients are two major causes of male infertility. Our research focuses on the Deleted in Azoospermia (DAZ) gene family on the Y chromosome long arm that is frequently deleted in infertile men. We perform functional analyses of the DAZ protein and study polymorphisms associated with the DAZ genes in the male population. Our results indicate that sister chromatid exchange plays a significant role in Y chromosome polymorphism. We also study two X-linked genes with testis-specific expression to test the hypothesis that the spermatogenic failure in Klinefelter syndrome patients is caused by increased expression of X-linked spermatogenesis genes during male germ cell development. We study the temporal and spatial expression of Tex11 and Usp26 during testis development, determine their subcellular localization, and generate null mutants to 66
  67. 67. elucidate their functions. Selected Recent Publication: 1. Yen, P.H. Advances in Y-chromosome mapping. Curr. Opin. Obstet. Gynecol. 11:275- 281, 1999. 2. Tsui, S., Dai, T., Warren, S.T., Salido, E.C., and Yen, P.H. Association of the infertility factor DAZL1 with actively translating polyribosomes. Biol. Reprod. 62:1655-1660, 2000. 3. Tsui, S., Dai, T., Roettger, S., Schempp, W., Salido, E.C., and Yen, P.H. Identification of two novel proteins that interact with germ-cell specific RNA-binding proteins DAZ and DAZL1. Genomics, 65:266-273, 2000. 4. Moro, E., Ferlin, A, Yen, P.H., Franchi, P.G., Palka, G., and Foresta C. Male infertility caused by a de novo partial deletion of the DAZ cluster on the Y chromosome. J. Clin. Endocrinol. Metab. 85:4069-4073, 2000 5. Roettger, S., Pasantes, J.J., Baldermann, C., Reichl, E., Yen, P.H., Hansmann, I., Schempp, W. Familial mosaicism of del(Y) and inv del(Y). Cytogenet. Cell Genet. 91:208-211, 2000. 6. Lue, Y., Rao, P.N., Sinha Hikim, A.P., Im, M., Salameh, W, Yen, P.H., Wang, C., and Swerdloff, R.S. Progressive loss of germ cells by apoptosis in XXY male mice: An experimental model for Klinefelter Syndrome. Endocrinology 142:1461-1470, 2001. 7. Yen, P. The fragility of fertility. NatureGenet. 29:243-244, 2001. 8. Vera, Y., Dai, T., Lue, Y., Sinha-Hikim, A.P., Salido, E.C., Swerdloff, R.S., and Yen, P.H. DAZAP1, a DAZ associated protein, shuttles between nucleus and cytoplasm during normal germ cell maturation. J. Andrology 23:622-628, 2002. 9. Roettger, S., Yen, P.H., and Schempp, W. A fiber-FISH contig spanning the non- recombining region of the human Y chromosome. Chrom. Res. 10:621-635, 2002. 10.Yen PH (2004) Putative biological functions of the DAZ family. Int. J. Androl. 27: 125- 129. 67
  68. 68. Taiwan International Graduate Program Molecular Medicine Program National Yang Ming University Faculty 68
  69. 69. Name in Chinese:張國威 Name in English:Kuo-Wei Chang Education:1983, DDS, National Yang-Ming University 1995, PhD, Department of Pathology, Northwestern University Affiliation:Department of Dentistry, National Yang-Ming University Title:Professor Tel:886-2-2826-7223 Fax:886-2-2826-4053 My Personal Homepage:http://www.ym.edu.tw/iob E-mail:ckcw@ym.edu.tw Fields of Specialty:Oral Pathology/Molecular Pathology Research Description: My investigation targets on oral carcinogenesis. Identification of tumor markers and karyotypic dissection of oral cancers have been my major research topics. Selected Recent Publication: 1. Liu SY, Yang SC, Yen CY, Chang KW* (2004, In press) Overexpression of Rac-1 small GTPase binding protein in areca quid-associated oral squamous cell carcinoma. J Oral Maxillofac Surg. 2. Wong YK, Lin SC, Liu CJ, Tzeng YS, Lin HC, Wong CY, Chang KW* (2003) Cyclin D1 genotype in areca-associated oral squamous cell carcinoma. J Oral Pathol Med 32: 265-70. 3. Chang, KW, Kao, SY, Tzeng RJ, Liu, CJ, Cheng AJ, Wong, YK, Yang SC and Lin SC* (2002) Multiple molecular alterations of FHIT in betel-associated oral squamous cell carcinoma. J Pathol 2002 196:300-6. 4. Lin SC, Chen YJ, Hsu MD, Chang CS, Liu TY, Lin CH and Chang KW* (2002) The chromosomal changes of oral squamous cell carcinoma associated with betel quid use. Oral Oncol 38: 266-73. 5. Chang KW, Lin SC, Chao SY, Kwan PC and Wong YK* (2001) Establishment and characterization of a new oral melanoma cell line (ME). Oral Oncol 37: 301-7. 69
  70. 70. 6. Chang KW, Lin SC, Kwan PS and Wong YK* (2000) Association of p53/p21waf1 expression with outcomes of veruccous leukoplakia in Taiwan. J Oral Pathol Med 29: 56-62. 7. Chang, KW, Sarraj S, Lin SC, Tsai, PI and Solt DB* (2000) p53 expression, p53 and Ha-ras mutation, and telomerase activation during nitrosamine-mediated hamster pouch carcinogenesis. Carcinogenesis 21: 1441-51. 8. Chang KW*, Lin SC, Wong YK, Liu TY and Chang CS (2000) Alterations of APC in oral squamous cell carcinoma in Taiwan. Int J Oral-Maxillofac Surg 29: 223-6. 9. Chang LY, Lin SC, Chang CS, Wong YK, Hu YC and Chang KW* (1999) Telomerase activity and in situ telomerase RNA expression in oral carcinogenesis. J Oral Pathol Med 28: 389-396. 10. Chen YJ, Lin SC, Kao T, Chang CS, Hong PS, Shieh TM and Chang KW* (In Revision) Genome profiling of oral squamous cell carcinoma and identification of Serpine1 (Plasminogen Activator Inhibitor-1, PAI-1) expression as an important event for oral carcinogenesis. J Pathol. 70

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