Malathy Shekhar, Ph.D.
421 E. Canfield Street, Suite 1148
Detroit, MI 48201
Mentoring: Brittany Haynes ( Graduated 08/04/2017 )
- Breast Cancer research is the major focus of my laboratory.
- Current projects: Studies on Rad6, a fundamental component of the postreplication DNA repair pathway: drug sensitivity/resistance mechanisms, gene regulation, stabilization/activation of Wnt/beta-catenin signaling, crosstalk between DNA repair pathways.
- Stromal-epithelial interactions and its role in hormonal sensitivity/resistance.
The long term goal of our research is to understand the molecular and cellular basis by which breast cancer cells become resistant to therapy. Our laboratory uses in vivo and in vitro three-dimensional breast cancer culture systems to investigate host stromal interactions and their role in breast cancer hormone sensitivity and progression. Our laboratory has investigated Rad6, an ubiquitin conjugating enzyme, and a fundamental component of postreplication DNA repair pathway in breast cancer development, progression and sensitivity to DNA damaging drugs. We showed a direct relationship between Rad6 expression, postreplication repair activity, and sensitivity to DNA damaging drugs. Our laboratory uncovered a novel function for Rad6 in beta-catenin stabilization and activation. Interestingly, Rad6 is a transcriptional target of beta-catenin, thus revealing a positive feedback loop between Rad6 gene expression and beta-catenin stabilization. Our current studies are focused on identifying small molecules with Rad6 inhibitory activity for breast cancer therapy.
Saadat N, Liu F, Haynes B, Nangia-Makker P, Bao X, Li J, Polin LA, Gupta S, Mao G, Shekhar MP. Nano-targeted Delivery of Rad6/Translesion Synthesis Inhibitor for Triple Negative Breast Cancer Therapy. Mol Can Ther , 2018 (in press).
Pharmacological targeting of RAD6 enzyme-mediated translesion synthesis overcomes resistance to platinum-based drugs. Sanders MA, Haynes B, Nangia-Makker P, Polin LA, Shekhar MP. J Biol Chem. 2017;292:10347-63.
Breast cancer complexity: implications of intratumoral heterogeneity in clinical management. Haynes B, Sarma A, Nangia-Makker P, Shekhar MP. Cancer Metastasis Rev. 2017 Jul 27.
Gold nanoparticle conjugated Rad6 inhibitor induces cell death in triple negative breast cancer cells by inducing mitochondrial dysfunction and PARP-1 hyperactivation: Synthesis and characterization. Haynes B, Zhang Y, Liu F, Li J, Petit S, Kothayer H, Bao X, Westwell AD, Mao G, Shekhar MPV. Nanomedicine. 2016;12:745-57
Crosstalk between translesion synthesis, Fanconi anemia network, and homologous recombination repair pathways in interstrand DNA crosslink repair and development of chemoresistance. Haynes B, Saadat N, Myung B, Shekhar MP. Mutat Res Rev Mutat Res. 2015;763:258-66.
Education and Training:
PhD in Biochemistry, The Indian Institute of Science, Bangalore, India.
Cancer Biology Courses Taught:
CB7210 Fundamentals of Cancer Biology
CB7220 Molecular Biology of Cancer Development (Course Director)
CB7300 Special Topics Breast Cancer (Course Director)
CB7300 Special Topics F31 Grant Writing Course
CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling