Malathy Shekhar, Ph.D.
421 E. Canfield Street, Suite 1148
Detroit, MI 48201
Mentoring: Brittany Haynes ( Senior Student )
- 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.
Heppner GH, Shekhar M. Tumor heterogeneity is fundamental to the tumor ecosystem. Oncology (Williston Park). 2014;28: 201366.
Rosner K, Mehregan DR, Kirou E, Abrams J, Kim S, Campbell M, Frieder J, Lawrence K, Haynes B, Shekhar MP. Melanoma Development and Progression Are Associated with Rad6 Upregulation and β -Catenin Relocation to the Cell Membrane. J Skin Cancer. 2014;2014:439205. Epub 2014 May 6.
Rosner K, Adsule S, Haynes B, Kirou E, Kato I, Mehregan DR, Shekhar MP. Rad6 is a Potential Early Marker of Melanoma Development. Transl Oncol. 2014:S1936-5233-00044-8. [Epub ahead of print]
Haagenson KK, Zhang JW, Xu Z, Shekhar MP, Wu GS. Functional analysis of MKP-1 and MKP-2 in breast cancer tamoxifen sensitivity. Oncotarget. 2014;5:1101-10.
Kothayer H, Elshanawani AA, Abu Kull ME, El-Sabbagh OI, Shekhar MP, Brancale A, Jones AT, Westwell AD. Design, synthesis and in vitro anticancer evaluation of 4,6-diamino-1,3,5-triazine-2-carbohydrazides and -carboxamides. Bioorg Med Chem Lett. 2013;23:6886-9.
Shekhar MP, Kato I, Nangia-Makker P, Tait L. Comedo-DCIS is a precursor lesion for basal-like breast carcinoma: identification of a novel p63/Her2/neu expressing subgroup. Oncotarget. 2013;4:231-41.
Nangia-Makker P, Raz T, Tait L, Shekhar MP, Li H, Balan V, Makker H, Fridman R, Maddipati K, Raz A. Ocimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matrix metalloproteases. Cancer Biol Ther. 2013;14:417-27.
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. 2013;12:373-83.
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