Malathy Puthan Shekhar
Malathy Puthan Shekhar
421 E. Canfield Street, Suite 1148
Detroit, MI 48201
• Breast Cancer and melanoma research
• Current projects:
Crosstalk between Translesion DNA synthesis and BRCA-dependent DNA repair pathways in triple negative breast cancer
Cell metabolism reprogramming in drug resistance
Elucidation of Rad6 involvement in Wnt/beta-catenin activation and melanomagenesis
The goal of our research is to understand the molecular and cellular basis of breast cancer and melanoma development and progression. Our laboratory uses in vivo and in vitro three-dimensional culture systems to investigate the contributions of host stromal interactions in melanoma and breast cancer development and therapy responses. These studies have uncovered a novel role for Rad6 in activation of canonical Wnt signaling besides its bonafide function in the translesion DNA synthesis (TLS) pathway. Our laboratory developed the first Rad6-selective small molecule inhibitor. Using this inhibitor and CrispR technology, we are interrogating Rad6/TLS crosstalk with DNA double strand break repair mechanisms and Rad6 crosstalk with canonical Wnt signaling, and developing strategies to harness its therapeutic potential for treatment of melanoma and triple negative breast cancer.
Haynes B, Gajan A, Nangia-Makker P, Shekhar MP. RAD6B is a major mediator of triple negative breast cancer cisplatin resistance: Regulation of Translesion synthesis/Fanconi anemia crosstalk and BRCA1 independence. BBA Mol Basis of Dis. 2020;1866:165561.
Gajan A, Martin C, Kim S, Joshi M, Michelhaugh S, Sloma I, Mittal S, Firestine S, Shekhar MP. Alternative splicing of Rad6B and not Rad6A is selectively increased in melanoma: Identification and functional characterization. Cells 2019;8:13175.
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;17:2586-97. .
Sanders MA, Haynes B, Nangia-Makker P, Polin LA, Shekhar MP. Pharmacological targeting of RAD6 enzyme-mediated translesion synthesis overcomes resistance to platinum-based drugs. J Biol Chem. 2017;292:10347-63.
Haynes B, Sarma A, Nangia-Makker P, Shekhar MP. Breast cancer complexity: implications of intratumoral heterogeneity in clinical management. Cancer Metastasis Rev. 2017 Jul 27.
Sanders MA, Brahemi G, Nangia-Makker P, Balan V, Morelli M, Kothayer H, Westwell AD, Shekhar MP. Novel inhibitors of Rad6 ubiquitin conjugating enzyme: Design, synthesis, identification and functional characterization. Mol Cancer Ther, 12:373-383, 2013.
Shekhar MP, Gerard B, Pauley RJ, Williams BO, Tait L. Rad6B is a positive regulator of β-catenin stabilization. Cancer Res, 68:1741-50, 2008.
Lyakhovich, A. and Shekhar, M.P. RAD6B overexpression confers chemoresistance: RAD6 distribution during cell cycle, and its redistribution to chromatin during DNA damage-induced response. Oncogene, 23:3098-3107, 2004.
Lyakhovich A, Shekhar MP. Supramolecular complex formation between Rad6 and proteins of p53 pathway during DNA damage-induced response. Mol Cell Biol, 23: 2463-2475, 2003.
Shekhar MP, Werdell J, Tait L. Interaction with endothelial cells is a prerequisite for branching ductal-alveolar morphogenesis and hyperplasia of preneoplastic human breast epithelial cells: Regulation by estrogen. Cancer Res. 60: 439-49, 2000.
PhD in Biochemistry, The Indian Institute of Science, Bangalore, India.
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
MBG7400 Molecular Biology of Cellular Signaling
BIO5640 Cancer Biology