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Sundar Venkatachalam F235 Walters Life Sciences |
Keywords:
Cancer, mouse models, cell cycle, chromatin remodeling, genomic instability
Research Area:
The primary focus of my research involves the developoment of mutant mouse models to understand the roles of specific genetic pathways involved in cancer formation.
Description of Research:
The historical utility of mouse models to study complex human disorders and the recent sequencing of the mouse genome are expected to have a major impact on research aimed at understanding the genetic basis of a variety of human disorders. Cancer is primarily a cell cycle disease that leads to unlimited cell division cycles. We are interested in understanding the genetic pathways that lead to unregulated cell proliferation and cancer. All or our research projects have a systems biology based approach in which we perform functional analysis of specific genes at the molecular, cellular, and organismal levels. To date, we have generated several mutant mouse models for cell cycle checkpoint and chromatin remodeling proteins. Graduate research projects for doctoral students who are interested in stydying the molecular and cellular basis of cancer formation are available.
Selected Publications:
- Venkatachalam S (2005) Aging, p53 and the '24 gene mutant': getting it right A reply to Vijg and Hasty. Aging Cell 4(6):335-8.
- Gentry A and Venkatachalam S (2005) Complicating the role of p53 in aging. Aging Cell 4: 157-160.
- Dumble M, Gatza C, Tyner S, Venkatachalam and Donehower LA (2004) Insights into aging obtained from p53 mutant mouse models. Ann N Y Acad Sciences 1019: 171-7.
- Moore L, Venkatachalam S, Vogel H, Watt J, Wu C, Jones SN and Donehower LA (2003) Cooperativity of p19ARF, Mdm2, and p53 in murine tumorigenesis. Oncogene 22(49): 7831-7837.
- Tyner S*, Venkatachalam S*, Choi J, Jones SN, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Park SH, Thompson T, Karsenty G, Bradley A and Donehower LA (2002) p53 mutant mice that display early aging associated phenotypes. Nature 415: 45-53. * equal contribution.
- Venkatachalam S, Tyner S, Harvey M, Sands A, Boley S, Recio L, French JE and Donehower LA (2001) Is p53 Haploinsufficient for Tumor Suppression? Implications for the p53+/- Mouse Model in Carcinogenicity Testing. Toxicol Pathology 20: S-147-154.
- Venkatachalam S, Tyner S and Donehower LA (2001) The p53 knockout mice as a cancer model. Tumor Models in Cancer Research: Cancer Drug Discovery and Development series Humana Press.
- Wani MA, Zhu QZ, El-Mahdy M, Venkatachalam S and Wani AA (2000) Enhanced sensitivity to anti-BPDE DNA damage correlates with decreased global genomic repair due to abrogated p53 function in human cells. Cancer Research 60(8): 2273-80.
- Venkatachalam S and Donehower LA (1998) Murine Tumor Suppressor models. Mutation Research 400: 391-407.
- Venkatachalam S, Shi Y, Jones SN, Vogel H, Bradley A, Pinkel D and Donehower LA (1998) Retention of wt p53 in tumors from p53 heterozygous mice: reduction in p53 gene dosage can promote cancer formation. EMBO Journal 16: 4657-4667.
- Venkatachalam S, Denissenko M, Wani AA (1997) Modulation of anti-BPDE mediated p53 accumulation by inhibitors of protein kinase C and poly(ADP-ribose)polymerase. Oncogene 14: 801-809.
- Denissenko M, Venkatachalam S, Ma Y and Wani AA (1996) Site-specific induction and repair of benzo[a]pyrene diol epoxide DNA damage in human H-ras proto-oncogene as revealed by restriction cleavage inhibition. Mutation Research 363: 27-42.
- Denissenko M, Venkatachalam S, Ma Y and Wani AA (1995) Single-tube immuno-capture and PCR of genotoxin-modified DNA: application to gene-specific damage analysis. Biotechniques 21(2): 187-188.
- Venkatachalam S, Denissenko M and Wani AA (1995) DNA repair in human cells: quantitative assessment of bulky anti-BPDE DNA adducts by non-competitive immunoassays. Carcinogenesis 16: 2029-2036.
- Denissenko M, Venkatachalam S, Yamasaki EF and Wani AA (1994) Assessment of DNA damage and repair in specific genomic regions by quantitative immuno-coupled PCR. Nucleic Acids Research 22: 2351-2359.
- Venkatachalam S and Wani AA (1994) Differential recognition of stereochemically defined base adducts by antibodies against anti-benzo[a]pyrene diol epoxide modified DNA. Carcinogenesis 15: 565-572.
- Venkatachalam S, Denissenko M, Alvi N and Wani AA (1993) Rapid activation of apoptosis in human promyelocytic leukemic cells by anti-benzo[a]pyrene diol epoxide induced DNA damage. Biochem. Biophys. Res. Commun. 197: 722-729.