Your SlideShare is downloading. ×
FTA page.doc.doc
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

FTA page.doc.doc

159
views

Published on


0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
159
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
0
Comments
0
Likes
0
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Dr. Francis Y.M. Choy B.Sc. (Microbiology, University of Manitoba), M.Sc., (Microbiology, University of North Dakota), Ph.D. (Biochemistry, University of North Dakota), Professor, Centre for Biomedical Research. Teaching: Cell Biology (Biol. 225), Genetics (Biol. 230), Molecular Genetics (Biol. 361), Biotechnolgy and Principles of Genetics (Biol. 401A), Human Molecular Genetics (Biol. 436), and Advanced Human Molecular Genetics (Biol. 536). Honours: Recipient of the Excellence in Teaching Award, Faculty of Science, University of Victoria, 2002. Research: Molecular genetics and enzymology of lysosomal storage diseases; molecular evolution of ß-glucosidase gene among primates; functional genomics. My research is focussed on the molecular biology and biochemistry of lysosomal enzymes, and their implications in lipid metabolism and mental function. I have chosen glucocerebrosidase as a model for my study. Glucocerebrosidase is of interest to me because its activity is profoundly deficient in an inherited metabolic disorder known as Gaucher disease prevalent among human, canine and rodent species. The natural substrate of glucocerebrosidase is glucocerebroside, an ubiquitous lipid present in the plasma membrane of all mammalian cells. It is not well understood why deficient activity of apparently the same enzyme will result in very different forms of Gaucher disease, varying from the non-neuronopathic and occasionally asymptomatic type 1 form to the devastating type 2 form that results in death before two years of age. My research objectives are to identify and characterize the various mutations from fibroblast cell lines of patient with different clinical subtypes, and to correlate the nature of the genetic defect(s) at the DNA level to the biochemical defect(s) at the protein-enzyme level. Data obtained will be useful towards a better understanding of the role of lysosomal enzyme in lipid metabolism, and in genetic counselling, and in the development of enzyme- and gene-replacement therapies. Since a pseudogene that shares 96% sequence similarity is found proximal to the functional gene in human, we are surveying and characterizing the pseudogene among primates and other mammalian species in order to understand more about its molecular evolution. Francis Y.M. Choy, Weimin Zhang, Hui-Ping Shi, Agnes Zay, Tessa Campbell, Nelson Tang, and Patrick Ferreira. Gaucher disease among Chinese patients: Review on genotype/phenotype correlation from 29 patients and identification of novel and rare alleles. Blood Cells, Molecules, and Diseases. In press, November, 2006. Graham B. Sinclair, Francis Y.M. Choy, Gareth Jevon, Karen E. Colobong, Derrick R. Randall, and Lorne A. Clarke. Generation of a conditional knockout
  • 2. model of murine glucocerebrosidase: Utility for the study of Gaucher disease. Molecular Genetics and Metabolism, accepted for publication, September, 2006. Bandsmer J, Campbell T, Cheyne I, and Choy, F.Y.M. 2006. Expression of active α-N-acetylglucosaminidase/TAT chimerae in Spodoptera frugiperda (Sf9) cells. Protein and Peptide Research Letter 13:353-356. Sinclair, G., Pfeiffer, T., Gligliatti, T., and Choy, F.Y.M. 2006. Secretion of human glucocerebrosidase from stable transfected insect cells using native signal sequences. Biochemistry and Cell Biology 84:148-156. Tang, N.S.L., Zhang, W., Grabowski, G.A., To, K.F., Choy, F.Y.M., Ma, S.L., and Shi, H.P. 2005. Novel mutations in type 2 Gaucher disease in Chinese patients and their functional characterization by in-vitro expression. Human Mutation 26(1):59-62, 2005. Full length article available on line from the journal at http://www3.interscience.wiley.com/homepages/38515/pdf/819.pdf Vaags, A., Campbell, T. and Choy, F.Y.M. 2005. HIV TAT variants differentially influence the production of glucocerebrosidase in Sf9 cells. 2005. Genetics and Molecular Research, 4(3): 491-495. Wafaei J.R. and Choy, F.Y.M. 2005. Glucocerebrosidase recombinant allele: Molecular evolution of the functional gene and pseudogene. 2005. Blood Cells, Molecules, and Diseases 35:277-285. Campbell, T. and Choy, F.Y.M. 2005. RNA interference: Past, present and future. Current Topics in Molecular Biology, 7:1-6. Campbell, T. and Choy, F.Y.M. 2004. Knockdown of chimeric glucocerebrosidase by green fluorescent protein-directed small interfering RNA.Genetics and Molecular Research, 3 (2): 282-287. Choy, F.Y.M. 2003. Identification of a promoter defect in the Gaucher Gene. Proceedings to the Symposium on Lysosomal Storage Disorders, 3:33-34. Choy, F.Y. M., Vaags, A., Wong, C., and Prassad, C., 2002. Identification of two novel mutations (L105R and C342R) in two type 1 Gaucher disease patients. Clinical Genetics, 61:229-231. Sinclair, G. and Choy, F.Y.M., 2002. Codon bias and utilisation by Pichia pastoris in the functional expression of human recombinant glucocerebroisdase. Protein Expression and Purification, 26 96-105. Campbell, T. and Choy, F.Y.M.. 2002. Screening of genomic library among prokaryotes. Journal of Molecular Microbiology and Biotechnology, 4 (6), 551- 554. Campbell, T. and Choy, F.Y.M. 2002. Expression of two green fluorescent protein variants in citrate-buffered media in Pichia pastoris. Analytical Biochemistry, 311:193-195. Campbell, T. and Choy, F.Y.M. (2001) Screening bacterial and yeast transformants using PCR. Biotechnology Journal International, 6(6):10-11. Campbell, T. and Choy, F.Y.M. (2001) Protein trafficking in the biosynthetic pathway. Molecular Biology Today, 2(3):67-76. Sinclair, G., Choy, F.Y.M., Ferreira, P. (2001) Heterologous expression and characterization of a rare Gaucher Disease mutation (P122S) from a Canadian aboriginal population using archival tissue samples. Molecular Genetics and Metabolism, 74:345-352.
  • 3. Campbell, Tessa N. and Choy, F.Y.M. (2001) Large-scale colony screening and insert orientation determination using PCR. Biotechniques 30:32-34. Campbell, Tessa N. and Choy, F.Y.M. (2001) The effect of pH on green fluorescent protein: A brief review. Molecular Biology Today 2:1-4. Choy, F.Y.M., Sharp, L., and Applegarth, D. (2000) Glycine cleavage enzyme complex: Rabbit H-protein cDNA sequence analysis and comparison to human, cow and chicken. Biochemistry and Cell Biology 78:175-180. Choy, F.Y.M., Sharp, L., and Applegarth, D. Nucleotide sequence of the complete coding region of rabbit (Oryctolagus caniculus) hydrogen carrier (H-) protein gene. Genebank Accession No. BankIt 318281 AF231451, May, 2000. Devost, N. and Choy, F.Y.M. (2000) Mutation analysis of Gaucher disease using dot blood samples on FTA filter papers. American Journal of Medical Genetics 94:417-420. Choy, F.Y.M., Wong, K., Vallence, D.H., and Baldwin, V. Novel point mutation (W184R) in neonatal type 2 Gaucher disease. (2000) Pediatric and Developmental Pathology 3:1-5. Choy, F.Y.M, Wong, K., and Shi, H.P. (1999) Glucocerebrosidase mutations among Chinese neuronopathic and non-neuronopathic Gaucher disease patients. American Journal of Medical Genetics 84:484-486. Sinclair G, Choy FYM, Humphries L (1998) A novel complex allele and two new point mutations in type 2 (acute neuronopathic) Gaucher disease. Blood Cells, Molecules, and Diseases 24: (20) 420-427. Choy FYM, Humphries ML, Ben-Yoseph Y (1998) Gaucher type 2 disease: Identification of a novel transversion mutation in a French-Irish patient. American Journal of Medical Genetics 78: (1) 92-93. Choy FYM, Humphries L, Ben-Yoseph Y (1998) A novel mutation (V191G) in a German-British type 1 Gaucher disease patient. Human Mutation vol.11, p.411- 412. Choy, F.Y.M., Humphries, M.L. and Shi, H.P. 1997. Identification of two novel and four uncommon missense mutations among Chinese Gaucher disease patients. Am. J. Med. Gen. 71: 172-178. Choy, F.Y.M., Humphries, M.L. and Ferreira, P. 1997. Novel Insertion Mutation in a Non-Jewish Caucasian Type 1 Gaucher Disease Patient. Am. J Med. Gen. 68: 211-215. Choy, F.Y.M., Linsey, J. and MacLeod, P.D. 1997. Gaucher disease: molecular screening of the glucocerebrosidase 1601G and 1601A alleles in Victoria, British Columbia, Canada. J Med. Gen. 34(1): 83-85. Choy, F.Y.M., Wei, C. and Levin, D. 1996. Gaucher Disease: Functional Expression of the Normal Glucocerebrosidase and Gaucher T1366G and G1604A Alleles in Baculovirus-Transfected Spodoptera frugiperda Cells. Am. J Med. Gen. 65: 184-189. Choy, F.Y.M. and Wei, C. 1995. Identification of a New Mutation (P178S) in an African-American Patient With Type 2 Gaucher Disease. Human Mutation 5: 345-347. Choy, F.Y.M. 1995. Type 2 Gaucher disease without the complex alleles. Journal of Clinical Laboratory Analysis 9:340-341.
  • 4. Choy, F.Y.M., Wei, C., Applegarth, D.A. and McGillirray, B.1994. DNA analysis of an uncommon missense mutation in a Gaucher disease patient of Jewish-Polish-Russian descent. American Journal of Medical Genetics 51: 156- 160. Choy, F.Y.M., Wei, C., Applegarth, D.A. and Yong, S.L., 1994. A new missense mutation in glucocerebrosidase exon 9 of a non-Jewish Caucasian type 1 Gaucher disease patient. Human Molecular Genetics 3: 821-823.

×