This document provides a publication list for Dr. Kevin D. Brown including 36 peer-reviewed publications from 1990 to 2008. The publications focus on characterizing cytoskeletal proteins, identifying their roles in cell cycle regulation and DNA damage response pathways, and investigating epigenetic silencing of tumor suppressor genes in cancer development.
“Possible Role Of Mitochondria DNA Mutations In Chronic Periodontitis”- Guest lecture as a part of AP State Periodontists Meet, 13/4/2010, Sri Sai College of Dental Surgery, Vikarabad, India.
Hairy research: Can hair tell the story about your health?Firhan Malik
In 2004-05, my honours thesis in Biochemistry, at Laurentian University, proposed using human hair samples to look at the concentration of heavy metals. We wanted to see to whether you could relate the metal concentration to a person's health status. These slides were originally used during my research proposal presentation. They provide evidence in the literature demonstrating links between metal concentrations and disease.
“Possible Role Of Mitochondria DNA Mutations In Chronic Periodontitis”- Guest lecture as a part of AP State Periodontists Meet, 13/4/2010, Sri Sai College of Dental Surgery, Vikarabad, India.
Hairy research: Can hair tell the story about your health?Firhan Malik
In 2004-05, my honours thesis in Biochemistry, at Laurentian University, proposed using human hair samples to look at the concentration of heavy metals. We wanted to see to whether you could relate the metal concentration to a person's health status. These slides were originally used during my research proposal presentation. They provide evidence in the literature demonstrating links between metal concentrations and disease.
Trade-Offs and Kinetic Control for Kinetic Proofreading Networks in Biologica...JoelMallory2
Complex biological processes are known for their remarkable ability to select the correct substrate out of a pool of chemically similar substrates. Indeed, the enzymes that mediate the biological processes of DNA replication, mRNA transcription, and protein translation can activate so-called kinetic proofreading (KPR) mechanisms to enhance their accuracy at the cost of additional energy expenditure from futile cycles. What physicochemical properties of the participating enzymes are most important for the functionality of these biological processes with KPR? Upon investigating trade-offs between four physicochemical properties, namely, error rate, speed, noise, and energy dissipation, for the T7 DNA polymerase and Escherichia coli ribosome, we determined that these properties cannot all be optimized at the same time due to trade-offs between them. In addition, we ranked the importance of the properties and found that the enzyme speed is most important followed by the energy dissipation, error rate, and noise. Furthermore, another intriguing aspect of biological systems is their ability to regulate the stationary fluxes of the elementary biochemical reactions, but the fundamental factors that govern the flux regulation are not well understood. Which features of the underlying free energy landscape control the stationary flux distribution of biological systems? We have proven that the ratios of the steady-state fluxes are invariant to energy perturbations of the intermediate states and are only affected by the transition state energy barriers on the free energy landscape. Therefore, we have established that the physicochemical properties that depend on the steady-state flux ratios (e.g., the error rate and energy dissipation) are purely under kinetic and not thermodynamic control. The invariance proof has revealed important implications for various drug perturbations and genetic mutations to influence the physicochemical properties of a wide range of biological processes. For example, we illustrated the generality of the invariance proof for protein folding motivated by hen egg-white lysozyme, aminoacyl-tRNA selection during protein translation in the E. coli ribosome, and the myosin-V motor protein that walks on actin cytoskeleton filaments.
Trade-Offs and Kinetic Control for Kinetic Proofreading Networks in Biologica...JoelMallory2
Complex biological processes are known for their remarkable ability to select the correct substrate out of a pool of chemically similar substrates. Indeed, the enzymes that mediate the biological processes of DNA replication, mRNA transcription, and protein translation can activate so-called kinetic proofreading (KPR) mechanisms to enhance their accuracy at the cost of additional energy expenditure from futile cycles. What physicochemical properties of the participating enzymes are most important for the functionality of these biological processes with KPR? Upon investigating trade-offs between four physicochemical properties, namely, error rate, speed, noise, and energy dissipation, for the T7 DNA polymerase and Escherichia coli ribosome, we determined that these properties cannot all be optimized at the same time due to trade-offs between them. In addition, we ranked the importance of the properties and found that the enzyme speed is most important followed by the energy dissipation, error rate, and noise. Furthermore, another intriguing aspect of biological systems is their ability to regulate the stationary fluxes of the elementary biochemical reactions, but the fundamental factors that govern the flux regulation are not well understood. Which features of the underlying free energy landscape control the stationary flux distribution of biological systems? We have proven that the ratios of the steady-state fluxes are invariant to energy perturbations of the intermediate states and are only affected by the transition state energy barriers on the free energy landscape. Therefore, we have established that the physicochemical properties that depend on the steady-state flux ratios (e.g., the error rate and energy dissipation) are purely under kinetic and not thermodynamic control. The invariance proof has revealed important implications for various drug perturbations and genetic mutations to influence the physicochemical properties of a wide range of biological processes. For example, we illustrated the generality of the invariance proof for protein folding motivated by hen egg-white lysozyme, aminoacyl-tRNA selection during protein translation in the E. coli ribosome, and the myosin-V motor protein that walks on actin cytoskeleton filaments.
Application Security Vulnerabilities: OWASP Top 10 -2007Vaibhav Gupta
General concepts of web application security vulnerabilities primarily based on OWASP Top 10 list-2007(I know its too old :-))
I, along with Sandeep and Vishal, presented on this at IIIT-Delhi college in April, 2014
1. Dr. Kevin D. Brown
Complete Publication Listing
(1/9/2017)
Peer-Reviewed Publications
Brown, K.D. and L.I. Binder. 1990. Identification and characterization of a novel mammalian intermediate
filament-associated protein. Cell Motil. Cytoskel. 17:19-33.
Brown, K.D. and L.I. Binder. 1992. Identification of the IFAP gyronemin as the actin-binding protein filamin:
implication for a novel mechanism of cytoskeletal interaction. J. Cell Sci. 102:19-30.
Brown, K.D., R.P. Zinkowski, S.E. Hays, and L.I. Binder. 1993. Actin-binding protein (ABP) is a component of
bovine erythrocytes. Cell Motil. Cytoskel. 24:100-108.
Brown, K.D. and L.I. Binder. 1993. Expression of the cytoskeletal-associated protein filamin in adult rat
organs. Exp. Cell Res. 209:325-332.
Brown, K.D., R.M.R. Coulson, T.J. Yen, and D.W. Cleveland. 1994. Cyclin-like accumulation and loss of the
putative kinetochore motor CENP-E results from coupling continuous synthesis with specific degradation
at the end of mitosis. J. Cell Biol. 125:1303-1312.
Balczon, R.D., L. Bao, W.E. Zimmer, K.D. Brown, R.P. Zinkowski, and B.R. Brinkley. 1995. The dissociation of
centrosome replication events from cycles of DNA synthesis and mitotic division in hydroxyurea-arrested
CHO cells. J. Cell Biol. 130:105-116.
Quinton, T.M., K.D. Brown, and W.L. Dean. 1996. Inositol 1,4,5-triphosphate-mediated calcium release from
platelet internal membranes is regulated by differential phosphorylation. Biochemistry 35:6865-6871.
Brown, K.D., K.W. Wood, and D.W. Cleveland. 1996. The kinesin-like protein CENP-E is kinetochore-
associated throughout poleward segregation during anaphase-A. J. Cell Sci. 109:961-969.
Gilad, S., A. Bar-Shira, R. Harnik, D. Shkedi, Y. Ziv, R. Hosravi, K. Brown, L. Vanagaite, G. Xu, M. Frydman,
M. Lavin, D. Hill, D.A. Tagle, and Y. Shiloh. 1996. Ataxia-telangiectasia: founder effect among North
African Jews. Hum. Mol. Genet. 5: 2033-2037.
Duesbery N.S., T. Choi, K. D. Brown, K.W. Wood, J. Resau, K. Fukasawa, D.W. Cleveland, and G.F. Vande
Woude. 1997. CENP-E is an essential kinetochore motor in maturing oocytes and is masked during Mos-
dependent, cell cycle arrest at metaphase II. Proc. Natl. Acad. Sci. USA 94: 9165-9170.
Brown, K.D., Y. Ziv, S.N. Sadandanan, L. Chessa, F.S. Collins, Y. Shiloh, and D.A. Tagle. 1997. The ataxia-
telangiectasia gene product, a constitutively expressed nuclear protein that is not upregulated following
genome damage. Proc. Natl. Acad. Sci. 94: 1840-1845.
Brown, K.D.*, C. Barlow*, C.-X. Deng, D. A. Tagle , and A. Wynshaw-Boris. 1997. Atm selectively regulates
p53-dependent cell cycle checkpoints and apoptotic pathways. Nature Genetics 17:453-
456. [*contributed equally]
Barlow, C., M. Liyanage, P. Moens, K. Nagashima, K.D. Brown, S. Rottinghaus, S. Jackson, D.
Tagle,T. Ried, and A. Wynshaw-Boris. 1998. Atm deficiency results in severe meiotic disruption as early
as leptonema of prophase I. Development 125:4007-4017.
Guru, S.C., J.S. Crabtree, K.D. Brown, K.J. Dunn, P. Manickam, N.B. Prasad, D. Wangsa, A.L. Burns, A.M.
Spiegel, S.J. Marx, W.J. Pavan, F.S. Collins, S.C. Chandrasekharappa. 1999. Isolation, genomic
organization and expression analysis of Men1, the murine homolog of the MEN1 gene. Mammal. Genome
10:592-596.
Brown, K.D., C. Barlow, and A. Wynshaw-Boris. 1999. Multiple ATM-dependent pathways: an explanation for
pleiotropy. Am. J. Hum. Genet. 64:46-50
Barlow, C., C. Ribaut-Barassin, T.A. Zwingman, A.J. Pope, K.D. Brown, J.W. Owens, D. Larson, E.A.
Harrington, A.M. Haeberle, J.Mariani, M. Eckhaus, K. Herrup, Y. Bailly, A. Wynshaw-Boris. 2000. ATM is
a cytoplasmic protein in mouse brain required to prevent lysosomal accumulation. Proc. Natl. Acad. Sci.
97:871-876.
2. Brown, K.D., T. Lataxes, S. Shangary, J. Mannino, J. Giardina, J. Chen, and R. Baskaran. 2000. Ionizing
radiation exposure results in upregulation of Ku70 via a p53 / ATM dependent mechanism. J. Biol. Chem.
275:6651-6656.
Shangary, S. , K.D. Brown , A.W. Adamson, S. Edmonson , T. Pandita , J. Yalowich , G.E. Taccioli, and R.
Baskaran. 2000. Regulation of DNA-PK activity by IR-activated Abl kinase is an ATM-dependent process.
J. Biol. Chem. 275:30163-30168.
Allen D.M., H. van Praag, J. Ray, Z. Weaver, C.J. Winrow, T.A. Carter, R. Braquet, E. Harrington, T. Ried, K.D.
Brown, F.H. Gage, and C. Barlow 2001. Ataxia telangiectasia mutated is essential during adult
neurogenesis. Genes Dev. 15:554-566.
Mannino, J.L., W.J. Kim, M. Wernick, S.V. Nguyen, R. Braquet, A.W. Adamson, Z. Den, W.-J. Kim, M.A.
Batzer, C.C. Collins, and K.D. Brown. 2001. Evidence for alternate splicing within the mRNA transcript of
the DNA damage-response kinase ATR. Gene 272:35-43.
Kim, W-J, Q.N. Vo, M. Shrivastav, T.A. Lataxes, and K. D. Brown. 2002. Aberrant methylation of the ATM
promoter correlates with increased radiosensitivity in a human colorectal tumor cell line. Oncogene
21:3864-3871.
Zhan, Q., Jin, S., Ng, B., Plisket, J., Shangary, S., Rathi, A., Brown, K.D., and R. Baskaran. 2002. Caspase-
mediated cleavage of BRCA1 during UV-induced apoptosis. Oncogene 21:5335-5345,
Adamson, A.W., W.-J. Kim, S. Shangary, R. Baskaran, and K. D. Brown. 2002. ATM is activated in
response to N-Methyl-N'-nitro-N-nitrosoguanidine-induced DNA alkylation. J. Biol. Chem. 277:38222-
28229.
Brown, K.D., A. Rathi, R. Kamath, D.I. Beardsley, Q. Zhan, J.L. Mannino, and R. Baskaran 2003. The
mismatch repair system is required for S-phase checkpoint activation. Nature Genet. 33:80-84.
Beardsley, D.I., Kowbel, D., Lataxes, T.A., Mannino, J.M., Kim, W.J., Xin, H., Collins, C.C. and Brown, K.D.
2003. Characterization of the Novel Amplified in Breast Cancer-1 (NABC1) Gene Product. Exp. Cell Res
290:402-413.
Ai, L. Vo, Q.N., Zuo, C., Suen, J.Y., Hanna, E. Brown, K.D. and Fan, C.-Y. 2004. Ataxia-Telangiectasia-
Mutated (ATM) Gene in Head and Neck Squamous Cell Carcinoma: Promoter Methylation with Clinical
Correlation in 100 Cases. Cancer Epidemiol Biomarkers Prev. 13:150-156
Wakeman, T.P., Kim, W.-J., Callens, S, Chiu, A., Brown, K.D., Xu, B. 2004. The ATM-SMC1 Pathway is
Essential for activation of the Chromium [VI]-induced S-Phase Checkpoint. Mutation Res. 554:241-
251.
Vo, Q.N., Kim, W.-J., Cvitanovic, L., Boudreau, D.A., Ginzinger, D.G., and Brown, K.D. 2004. The ATM
gene is a target for epigenetic silencing in locally advanced breast cancer. Oncogene 23:9432-9437.
Singh, S.V., Antosiewicz, A.H., Singh, A.V., Lew, K.L., Kamath, R., Brown, K.D., Zhang, L., Baskaran R. 2004.
Sulforaphane-Induced G2/M Phase Cell Cycle Arrest Involves Checkpoint Kinase 2 Mediated
Phosphorylation of Cdc25C. J. Biol. Chem. 279:25813-22.
Vaidyanathan, G., Cismowski, M., Wang, G., Vincent, T.S., Brown, K.D., Lanier, S.M. 2004. The Ras-related
protein AGS1/RASD1 suppresses cell growth. Oncogene 23:5858-63
Kim, W.-J., Adamson, A.W., Beardsley, D.I., and Brown, K.D. 2005. The monofunctional alkylating agent
N-methyl-N’-nitro-N-nitrosoguanidine triggers apoptosis through p53-dependent and -independent
pathways. Toxicol. Appl. Pharm. 202:84-98.
Adamson, A.W., Beardsley, D.I., Kim, W-J, Gao, Y., Baskaran, R. and Brown, K.D. 2005. Methylator-
Induced, Mismatch Repair-Dependent G2 Arrest is Activated Through Chk1 and Chk2. Mol. Biol. Cell.
16:1513-26
Beardsley, D.I., Kim, W.-J. and Brown, K.D. 2005. N-methyl-N’-nitro-N-nitrosoguanidine activates cell
cycle arrest through distinct mechanisms activated in a dose-dependent manner. Mol. Pharm.
68:1049-1060
3. Bolt, J., Vo, Q.N., Kim, W.-J., McWhorter, A.J., Thomson, J., Hagensee, M.E., Friedlander, P., Brown,
K.D., Gilbert, J. 2005. The ATM/p53 pathway is commonly targeted for inactivation in squamous cell
carcinoma of the head and neck (SCCHN) by multiple molecular mechanisms. Oral Oncology 41:1013-
1020.
Turner J, Koumenis C, Kute TE, Planalp RP, Brechbiel MW, Beardsley DI, Cody B, Brown KD, Torti FM, Torti
SV. 2005. Tachpyridine, a metal chelator, induces G2 cell cycle arrest, activates checkpoint kinases, and
sensitizes cells to ionizing radiation. Blood 106:3191-3199.
Ai, L, Tao, Q, Zhong, S, Fields, CR, Kim, W-J, Lee, MW, Cui, Y, Brown, KD and Robertson, KD. 2006.
Inactivation of Wnt inhibitory factor-1 (WIF1) expression by epigenetic silencing is a common event in
breast cancer Carcinogenesis 27:1341-48.
Ai, L, Kim, W-J, Kim,
T-Y, Fields, CR, Massoll, NA, Robertson, KD, Brown, KD. 2006. Epigenetic silencing of
the tumor suppressor cystatin M occurs during breast cancer progression. Cancer Research 66:7899-
7909.
Kim, WJ, Rajasekaran, B, and Brown, KD. 2007. MLH1 and ATM-dependent MAP kinase signaling is
activated through c-Abl in response to the alkylator N-methyl-N’-nitro-N-nitrosoguanidine J. Biol. Chem.
282:32021-32031.
Lee, MW, Kim, WJ, Beardsley, DI and Brown, KD. 2007. N-methyl-N’-nitro-N-nitrosoguanidine activates
both caspase-dependent and independent cell death mechanisms in human fibroblasts DNA and Cell
Biol. 26: 683-694.
Brown, KD and Robertson, KD. 2007. DNMT1 knockout delivers a strong blow to genome stability and
cell viability. Nature Genetics 39:289-90.
Palii, S., Van Emburgh, B.O., Sankpal, U.T, Brown, K.D. and Robertson, K.D. 2008. The DNA methylation
inhibitor 5-aza-2’-deoxycytidine (5-azadC) induces reversible genome-wide DNA damage that is distinctly
influenced by DNA methyltransferases (DNMTs) 1 and 3B. Molec. Cell Biol. 28:752-71.
Zheng, L., Asprodites, N., Keene, A.H., Rodriguez, P., K.D. Brown, and Davila, E. 2008. TLR engagement on
CD4 T lymphocytes represses γ-radiation–induced apoptosis through activation of checkpoint kinase
response elements. Blood 111(5):2704-13.
Ai, L., Kim, W-J, Demircan,
B., Dyer, L.M., Bray, K.J., Skehan, R.R, Massoll, N.A., Brown, K.D. 2008. The
transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is
epigenetically silenced in breast cancer. Carcinogenesis 29(3):510-8.
Qiu, J., Ai, L., Ramachandran, C., Yao,B., Gopalakrishnan, S., Fields, C.R., Delmas, A.L,. Dyer, L.M., Melnick,
S.J., Yachnis, A.T., Schwartz, P.H., Fine, H.A., Brown, K.D. and Robertson, K.D. 2008. Invasion
suppressor cystatin E/M (CST6): High-level cell type-specific expression in normal brain and epigenetic
silencing in brain tumors. Lab Invest. 9:910-25.
Demircan, B., Dyer, LM, Gerace, M, Lobenhofer, E.K., Robertson, KD and Brown, KD. 2009. Comparative
epigenomics of human and mouse mammary tumors. Genes, Chrom and Cancer 48:83-97.
Orlando, FA, Brown, KD. 2009. Unraveling Breast Cancer Heterogeneity Through Transcriptomic and
Epigenomic Analysis. Ann. Surg. Oncol. 16(8):2270-9.
Darst RP, Pardo CE, Ai L, Brown KD, Kladde MP. 2010. Bisulfite sequencing of DNA. Curr Protoc Mol Biol.
Chapter 7:Unit 7.9.1-17.
Jiang Z, Jin S, Yalowich JC, Brown KD, Rajasekaran B. 2010. The Mismatch Repair System Modulates
Curcumin Sensitivity through Induction of DNA Strand Breaks and Activation of G2-M Checkpoint. Mol
Cancer Ther. 9:558-68.
Dyer LM, Schooler KP, Ai L, Klop C, Qiu J, Robertson KD, Brown KD. 2011. The transglutaminase 2 gene is
aberrantly hypermethylated in glioma. J Neurooncol. 101:429-40.
Ha K, Lee GE, Palii SS, Brown KD, Takeda Y, Liu K, Bhalla KN, Robertson KD. 2011. Rapid and transient
recruitment of DNMT1 to DNA double-strand breaks is mediated by its interaction with multiple components
of the DNA damage response machinery. Hum Mol Genet. 20:126-40.
4. Delmas, AL, Riggs, BM, Pardo, CE, Dyer, LM, Darst, RP, Izumchenko, E, Monroe, M, Hakam, A, Kladde, MP,
Siegel, EM and Brown, KD. 2011. WIF1 is a Frequent Target for Epigenetic Silencing in Squamous Cell
Carcinoma of the Cervix. Carcinogenesis 32:1625-33.
Chen M, Shabashvili D, Nawab A, Yang SX, Dyer LM, Brown KD, Hollingshead M, Hunter KW, Kaye FJ,
Hochwald SN, Marquez VE, Steeg P, Zajac-Kaye M. 2012. DNA methyltransferase inhibitor, zebularine,
delays tumor growth and induces apoptosis in a genetically engineered mouse model of breast cancer.
Mol Cancer Ther. 11:370-82.
Ai, L, Skehan, RR, Saydi, J, Lin, T, and Brown, KD. 2012. Ataxia-Telangiectasia, Mutated (ATM) / Nuclear
Factor Kappa light chain enhancer of activated B cells (NF kappaB) Signaling Controls Basal and DNA
Damage-Induced Transglutaminase 2 Expression. J. Biol. Chem 287:18330-41.
Izumchenko E, Saydi J, and KD Brown. 2012. Exonuclease 1 (Exo1) is required for activating response to
SN1 DNA methylating agents. DNA Repair 11(12):951-64.
Brown, KD. 2013. Transglutaminase 2 and NF-κB: an odd couple that shapes breast cancer phenotype.
Breast Cancer Res Treat. 137(2):329-36.
Ai L, Kim WJ, Alpay M, Tang M, Pardo CE, Hatakeyama S, May WS, Kladde MP, Heldermon CD, Siegel
EM, Brown KD. 2014. TRIM29 suppresses TWIST1 and invasive breast cancer behavior. Cancer Res.
74(17):4875-87
Salz T, Deng C, Pampo C, Siemann D, Qiu Y, Brown K, Huang S. 2015. Histone methyltransferase hSETD1A
is a Novel Regulator of Metastasis in Breast Cancer. Mol Cancer Res. 13(3):461-9
Alpay M, Backman LR, Cheng X, Dukel M, Kim WJ, Ai L, Brown KD. 2015. Oxidative stress shapes breast
cancer phenotype through chronic activation of ATM-dependent signaling. Breast Cancer Res Treat.
151(1):75-87
Cheng X, Byrne M, Brown KD, Konopleva MY, Kornblau SM, Bennett RL, May WS. 2015. PKR inhibits the
DNA damage response, and is associated with poor survival in AML and accelerated leukemia in NHD13
mice. Blood. 126(13):1585-94.
Dükel M, Streitfeld WS, Tang TC, Backman LR, Ai L, May WS, Brown KD. 2016. The Breast Cancer Tumor
Suppressor TRIM29 is Expressed via ATM-Dependent Signaling in Response to Hypoxia. J Biol Chem.
291(41): 21541-52.
Dyer LM, Ai L, Xu J, Kim WJ, Tang M, Reinhard MK, Backman LRF, Treiber N, Scharffetter-Kochanek K,
Leeuwenburgh C, McKinnon PJ, and Brown KD. ATM is required for SOD2 Expression and Homeostasis
within the Lactating Mammary Gland. Developmental Biology (in revision)
Book Chapters
Balczon, R.D., L. Bao, W.E. Zimmer, K.D. Brown, R.P. Zinkowski, and B.R. Brinkley. 1994. Analysis of
centrosome replication events in mammalian cells. In : The Cell Cycle: Regulators, Targets, and Clinical
Applications. V.W. Hu, ed. Plenum Press, New York.
Brown, K.D. and D.A. Tagle. 1997. Molecular perspectives on cancer, the cell cycle and the inherited disorder
ataxia-telangiectasia. In: Progress in Clinical and Biological Research Vol. 369: Etiology of Breast and
Gynecological Cancers. C.M. Aldaz, M. N. Gould, J. McLachlan, T.J. Slaga, eds. Wylie-Liss, New York.
Shivastav, M. and K.D. Brown. 2002. ATM and cancer risk. In : Recent Research Developments in Human
Genetics. Research Signpost, Kerala, India. 1:63-81.
Demircan B, and KD Brown. 2008. Cancer Epigenetics. In: Encyclopedia of Cancer. Ed: Manfred Schwab.
Springer-Verlag, New York, NY.
Orlando, FA, Dyer, LM, and KD Brown 2009. Chapter 12 - Epigenetic Analysis in Breast Cancer Progression.
In: Epigenetics: Mechanisms, Functions and Human Effects. Eds: B. Pinter and Z. Meszaros. Nova
Science Publishers Hauppauge, New York.
Orlando, FA, Dyer, LM, and KD Brown. 2009. Chapter 13 - Cancer Epigenetics. In: Epigenetics:
Mechanisms, Functions and Human Effects. Eds: B. Pinter and Z. Meszaros. Nova Science Publishers
Hauppauge, New York.