Dharini Shah

Education

Post-doctoral Associate, Mentor – Prof. Leona D. Samson August 2003 - Present Biological Engineering Division, Center for Environmental Health Sciences Massachusetts Institute of Technology

Doctor of Philosophy (Ph.D.) Advisor – Prof. Barry Gold - April 2003 Eppley Institute for Research in Cancer and Allied Diseases & Department of Pharmaceutical Sciences. University of Nebraska Medical Center.

B.S. in Pharmaceutical Sciences - August 1997 Bombay College of Pharmacy, University of Bombay, Mumbai – India

CDP research

Systems Biology and Computational approach to understand DNA damage responsive network

This project involves constructing a predictive model in human lymphoblastoid cell lines that would correlate dynamic intracellular signaling to different phenotypic responses like survival, apoptosis and necrosis in response to DNA damaging agents. Optimized highly quantitative western analysis for measuring activation of numerous DNA damage responsive proteins by either measuring phosphorylation status or their localization in subcellular compartments. Established multiple cell death (apoptosis, necrosis) assays using multicolor FACS analysis. Developed an HPLC and LC/MS method to identify and quantify DNA lesions in femtomolar ranges and quantify strand breaks by pulse gel electrophoresis that are results of DNA lesions processing. Currently I am learning modeling techniques like Principal Component Analysis/ Partial Least Regression Analysis and Ordinary Differential Equations (ODEs) by participating in a modeling course in BE department at MIT.

Mouse models to understand interaction of DNA repair and DNA damage checkpoints machinery

Samson lab has generated mice that are WT, single mutant in different DNA repair machinery and cell cycle checkpoints and double mutants that are both DNA repair and checkpoint nulls. Identified drastic differences in contribution of cell cycle checkpoints and DNA repair proteins that is cell type specific (bone marrow and mouse embryonic fibroblast) and DNA alkylating agent specific

Publications

Longerich S, Meira L, Shah D, Samson LD, and Storb U. Alkyladenine DNA glyocsylase (Aag) in somatic hypermutation and class switch recombination. (2007) DNA Repair (in press)

Monti, P., Iannone, R., Campomenosi, P., Ciribilli, Y., Inga, A., Varadarajan, S., Shah, D., Menichini, P., Gold, B., and Fronza, G. Influences of nucleotide and base excision repair defects on the lethality and mutagenicity induced by Me-lex, a sequence selective N3-adenine methylating agent (2004) Biochemistry 43, 5592-5599.

Shah, D., and Gold B. Evidence in Escherichia coli that N3-methyladenine lesions and cytotoxicity induced by a minor groove binding methyl sulfonate ester can be modulated in vivo by netropsin. (2003) Biochemistry 42, 12610-12616.

Varadarajan, S. *, Shah, D.*, Dande, P., Settless, S., Chen, F-X., Fronza, G., and Gold, B. DNA damage and cytotoxicity induced by minor groove binding methyl sulfonate esters. (2003) Biochemistry 42, 14318-14327. *Both authors contributed equally.

Monti, P., Campomenosi, P., Ciribilli, Y., Iannone.R., Inga, A., Shah, D., Scott, G., Burns, P., Menichini, P., Abbondandolo, A., Gold, B., and Fronza, G. Influences of Base Excision Repair Defects on the lethality and mutagenicity induced by a Me-lex, a sequence-selective N3-adenine methylating agent (2002) Journal of Biological Chemistry 277, 28663-28668.

Shah, D., Kelly, J., Zhang, Y., Dande, P., Martinez, J., Ortiz, G., Fronza, G., Tran, H., Soto, A., Marky, L., and Gold, B. Evidence in Escherichia coli that N3-methyladenine lesions induced by a minor groove binding methyl sulfonate ester can be processed by both Base and Nucleotide Excision Repair (2001) Biochemistry 40 (6), 1796-1803: Erratum, Biochemistry (2001) 40 (27), 8180.

Kelly, J., Inga, A., Chen, F. X., Dande, P., Shah, D., Monti, P., Aprile, A., Burns, P.A., Scott, G., Abbondolo, A., Gold, B., and Fronza, G. Relationship between DNA methylation and mutational patterns induced by a sequence selective minor groove methylating agent (1999) Journal of Biological Chemistry 274, 18327-18334.

Kelly, J., Shah, D., Chen, F.X., Wurdeman. R. and Gold, B. Quantitative and qualitative analysis of DNA methylation at N3-adenine by N-methyl-N-nitrosourea (1998) Chemical Research in Toxicology 11, 1481-1486.