Malathy Puthan Shekhar
Position Title
Professor
Basic Science
Office Location
Karmanos Cancer Institute
Elliman Building, RM -1148
421 E Canfield
Detroit, MI 48201
Mailing Address
Office Phone
313-578-4326
Office Fax
313-831-7518Education Training
Education
(1985) Ph.D. Biochemistry, Indian Institute of Science, Bangalore, India
(1979) M.Phil Biochemistry, University of Madras, India
(1978) M.Sc. Biochemistry, University of Madras, India
(1976) B.Sc. (Major: Chemistry; Ancillary, Physics), Stella Maris College, University of Madras, India
Postgraduate Training
(1986-1989) Research Associate, Dept. of Animal Science, University of Missouri-Columbia, Columbia, MO
(1985-1986) Post-Doctoral Fellow, Dept. of Obstetrics and Gynecology, Kansas University Medical Center, Kansas City, KS
Professional Experience
Faculty Appointments
(2015-Present) Professor, Department of Oncology, Wayne State University School of Medicine, Detroit, MI
(2015-Present) Professor, Department of Pathology, Wayne State University School of Medicine, Detroit, MI
(1998-Present) Member of Cancer Biology Graduate Program, Wayne State University
(2011-2015) Associate Professor (Tenured 2011), Department of Pathology, Wayne State University School of Medicine
(2010-2015) Associate Professor (Tenured 2011), Department of Oncology, Wayne State University School of Medicine
(1999-2015) Associate Professor, Department of Pathology, Wayne State University
(1995-1999) Assistant Professor, Department of Pathology, Wayne State University
Hospital or Other Professional Appointments
(2013-Present) Member, Molecular Therapeutics Program, Karmanos Cancer Institute
(2006-Present) Member, Environmental Health Sciences Center in Molecular and Cellular Toxicology
(1997-Present) Member, Breast Cancer Biology Program, Karmanos Cancer Institute
(2009-2012) Member, Molecular Biology & Genetics Program, Karmanos Cancer Institute
(1994-1997) Assistant Member, Breast Cancer Program, Michigan Cancer Foundation
(1989-1994) Assistant Member, Molecular Biology Program, Michigan Cancer Foundation
Major Professional Societies
(2007-Present) American Association of Indian Scientists in Cancer Research
(2003-Present) American Association for Cancer Research
(2003-Present) New York Academy of Sciences
(2000-Present) American Association for the Advancement of Science
(2000-Present) Women in Cancer Research
Honors and Awards
(2010) Heroes of Breast Cancer Award The Michael J Brennan Award for Scientific Distinction
(2006, 2014) Wayne State University School of Medicine Teaching Award
(1997) President's award for excellence in Basic Research, Karmanos Cancer Institute
(1985-1987) Rockefeller Foundation Fellowship
Courses taught
CB 7210: Fundamentals of Cancer Biology
CB 7220: Molecular Biology of Cancer Development
CB 7300 F31: Special Topics in Cancer Biology - Grant Writing Minicourse
CB 7300: Special Topics in Cancer Biology - Clinical and Basic Aspects of Breast Cancer
CB 7460: Mechanisms of Neoplasia - Alterations to Cellular Signaling
MGG 7400: Molecular Biology of Cancer Signaling
Research Interests
The long term goal of our research is to understand the molecular and cellular basis of breast cancer development and therapy response/resistance mechanisms. 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 development, progression and hormonal response. We identified Rad6B, an ubiquitin conjugating enzyme, and a fundamental component of postreplication DNA repair pathway, to play a critical role in breast cancer development, progression and chemosensitivity. Studies from our laboratory also uncovered a novel function for Rad6B in beta-catenin stabilization and transcriptional activation. Interestingly, Rad6B is a transcriptional target of beta-catenin, thus revealing a positive feedback loop between Rad6B gene expression and beta-catenin stabilization. We have recently identified a small molecule inhibitor of Rad6, and our current studies are focused on unraveling crosstalk between BRCA/Fanconi anemia and Rad6 DNA repair pathways in triple negative breast cancer.
Publications
1. Haynes B, Zhang Y, Liu F, Li J, Petit S, Xun B, Westwell AD, Mao G. Shekhar MP. 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. Nanomedicine: Nanotechnology, Biology and Medicine, 12:745-757, 2016. doi: 10.1016/j.nano.2015.10.010. [Epub ahead of print]
2. Sanders MA, Brahemi G, Nangia-Makker P, Balan V, Morelli M, Kothayer H, Westwell A, Shekhar MP. Novel inhibitors of Rad6 Ubiquitin Conjugating Enzyme: Design, synthesis, identification and functional characterization. Mol Cancer Ther 12:373-383, 2013. PMID: 23339190. (featured on the cover).
3. Shekhar MP, Kato I, Nangia-Makker P, Tait L. Comedo-DCIS is a precursor lesion for basal-like breast cancer: Identification of a novel p63/Her2/neu expressing subgroup. Oncotarget 4:231-241, 2013. PMID: 23548208.
4. Shekhar MP, Gerard B, Pauley RJ, Williams BO, Tait L. Rad6B is a positive regulator of beta-catenin stabilization. Cancer Res. 2008 Mar 15;68(6):1741-50. PMID: 18339854.
5.Shekhar MP, Santner S, Carolin-Amirikia K., and Tait, L. Direct involvement of breast tumor fibroblasts in the modulation of tamoxifen sensitivity. Amer. J Pathol. 2007 May;170(5):1546-60. PMID: 17456761.
6. Shekhar MP, Tait, L., and Gerard, B. Essential role of TCF/b-catenin in regulation of Rad6B: A potential mechanism for Rad6B overexpression in breast cancer cells. Mol. Cancer Res. 2006 Oct;4(10): 729-45.PMID: 17050667.
7. Lyakhovich A, Shekhar MP. RAD6B overexpression confers chemoresistance: RAD6 distribution during cell cycle, and its redistribution to chromatin during DNA damage-induced response. Oncogene, 23:3098-3107, 2004. PMID: 14981545.
8. Lyakhovich A, Shekhar MP (2003) Supramolecular complex formation between Rad6 and proteins of the p53 pathway during DNA damage-induced response. Mol. Cell Biol. 2003 Apr:23(7): 2463-2475. PMID: 12640129.
9. Shekhar MP, Lyakhovich A, Heng H, Visscher DW, Kondrat, N. RAD6 overexpression induces centrosome amplification, abnormal mitosis, aneuploidy and transformation. Cancer Res, 62:2115-2124, 2002. PMID: 11929833.
10. Shekhar MP, Werdell J, Santner S, Pauley RJ, Tait L. Breast stroma plays a dominant regulatory role in breast epithelial growth and differentiation: implications for tumor development and progression. Cancer Res., 61: 1320-1326, 2001. PMID: 11245428.
https://www.ncbi.nlm.nih.gov/sites/myncbi/10ezcneTh0F5S/bibliography/46314279/public/?sort=date&direction=descending