Office LocationRoom B4334, Research & Development Section
John D. Dingell VA Medical Center,
4646 John R,
Detroit, MI 48201
(1987) Ph.D. Molecular Biology, Imperial College of Science , Technology and Medicine, University of London, London, U.K.
(1984) M.Sc. Biochemistry, University College London, University of London, U.K.
(1988-1990) Post-doctoral Associate, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
(1987-1988) Postdoctoral Associate, Center for Environmental Health Sciences, M.I.T. Cambridge, MA, USA
(2010-Present) Professor (tenured), Department of Oncology (Primary Appointment), and the Department Internal Medicine (Secondary Appointment), Wayne State University School of Medicine, Detroit, MI.
(2001-Present) Health Science Specialist (Research), Department of Veterans Affairs, Room B4334, John D. Dingell VA Medical Center, Detroit, MI
(1998-2010) Associate Professor (tenured), Barbara Ann Karmanos Cancer Institute (Primary Appointment), and the Department Internal Medicine (Secondary Appointment), Wayne State University School of Medicine, Detroit, MI.
(1994-1998) Assistant Professor, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
(1991-1994) Assistant Professor, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
Hospital or Other Professional Appointments
(1998-Present) Member, Barbara Ann Karmanos Cancer Institute, Detroit, MI
CB 7220: Molecular Biology of Cancer Development
CB 7460: Mechanisms of Neoplasia - Alterations to Cellular Signaling
MGG: Cellular Signaling
My research focuses on studying pathways and molecular mechanisms regulating cell growth/survival and death/apoptosis. By utilizing a functional gene-knockout approach we identified and characterized a novel, apoptosis inducing protein termed CARP-1/CCAR1. CARP-1 regulates apoptosis signaling induced by an apoptogenic retinoid CD437, Adriamycin, Etoposide, but not by chemotherapy agents such as Cisplatin. CARP-1 also mediates apoptosis by EGFR-targeted therapeutics such as Gefitinib. CARP-1 is a tyrosine and well as serine phoshorylated protein that functions in part by interacting with multiple regulators of cell growth and apoptosis signaling. The growing list of CARP-1 interactors include the tumor suppressor protein p53, cell cycle regulatory Anaphase Promoting Complex (APC)-2, nuclear factor kappa B upstream kinase subunit gamma (IKKgamma/NEMO), stress-activated map kinase p38, nuclear receptors of steroid/thyroid superfamily, 14-3-3, and TAZ, proteins. Elucidation of CARP-1 interactions with APC/C permitted us to identify a novel class of small molecule compounds termed CARP-1 Functional Mimetics (CFMs). CFMs function in part by binding with CARP-1 and prevent its interaction with APC/C, and stimulate G2M arrest and apoptosis in cancer cells. Our CFM compounds are inhibitors of a variety of cancers including the triple-negative breast, non-small cell lung cancers, mesotheliomas, as well as medulloblastomas and neuroblastomas. Thus our CFM compounds and their future analogs provide us with valuable tools to develop novel strategies for effective management of a variety of cancers. Our on-going studies are focused to further define the cell cycle and apoptosis mechanisms that involve CARP-1, and exploitation of this knowledge to develop strategies for treatment of range of pathologies including the drug-resistant cancers.
1. Muthu, M., Cheriyan, V.T., Rishi, A.K. CARP-1/CCAR1: A biphasic regulator of cancer cell growth and apoptosis. Oncotarget 6(9): 6499-510, 2015.
2. Muthu, M., Somagoni, J.M., Cheriyan, V.T., Munie, S., Levi, E., Ashour, A.E., Alafeefy, A.M., Sochacki, P., Polin, L.A., Reddy, K.B., Larsen, S.D., Singh, M., and Rishi, A.K. Identification and testing of novel CARP-1 functional mimetic compounds as inhibitors of non-small cell lung and triple-negative breast cancers. J. Biomed. Nanotechnol. 11: 1608-1627, 2015.
3. Muthu, M., Cheriyan, V.T., Munie, M., Levi, E., Frank, J., Ashour A.E., Singh, M., Rishi, A.K. Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics. PLoS One 9(7): e102567, 2014.
4. Jamal, S., Cheriyan, V.T., Muthu, M., Munie, S., Levi, E., Ashour, A.E., Pass, H.I., Wali, A., Singh, M., Rishi, A.K. CARP-1 functional mimetics are a novel class of small molecule inhibitors of malignant pleural mesothelioma cells. PLoS One 9 (3), e89146, 2014.
5. Ashour, A.E., Jamal, S., Cheryan, V.T., Muthu, M., Zoheir, K.M.A., Alafeefy, A.M., Abd-allah, A.R., Levi, E., Tarca, A.L., Polin, L.A., Rishi, A.K. CARP-1 functional mimetics: A novel class of small molecule inhibitors of medulloblastoma cell growth. PLoS One 8(6), e66733, 2013.
6. Puliyappadamba, V.T, Wu, W., Bevis, D., Zhang, L., Polin, L., Kilkuskie, R., Finley Jr., R.L., Larsen, S.D., Levi, E., Miller, F.R., Wali, A., Rishi, A.K. Antagonists of anaphase promoting complex (APC)-2-cell cycle and apoptosis regulatory protein (CARP)-1 interaction are novel regulators of cell growth and apoptosis. J. Biol. Chem., 286 (44): 38000-38017, 2011.
7. Zhang, X., Tang, N., Hadden, T. J., and Rishi, A.K. Akt, FoxO and regulation of apoptosis. Biochimica et Biophysica Acta, Molecular Cell Research, 1813: 1978-1986, 2011.
8. Zhang, L., Levi, E., Majumder, P., Yu, Y., Aboukameel, A., Du, J., Xu, H., Mohammad, R.M., Hatfield, J.S., Wali, A., Adsay, V., Majumdar, A.P.N., and Rishi, A.K. TAT-tagged Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 peptides suppress growth of human breast cancer cells in vitro and in vivo. Mol. Cancer Ther. 6(5): 1661-1672, 2007.
9. Rishi, A.K., Zhang, L., Yu, Y., Jiang, Y., Nautiyal, J., Wali, A., Fontana, J.A., Levi, E., Majumdar, A.P.N. Cell cycle and apoptosis regulatory protein (CARP)-1 is involved in apoptosis signaling by epidermal growth factor receptor. J. Biol. Chem., 281(19): 13188-98, 2006.
10. Rishi, A.K., Zhang, L., Boyanapalli, M., Wali, A., Mohammad, R.M., Yu, Y., Fontana, J.A., Hatfield, J.S., Dawson, M.I., Majumdar, A.P.N., and Reichert, U. Identification and characterization of a Cell-Cycle and Apoptosis Regulatory Protein (CARP)-1 as a novel mediator of apoptosis signaling by retinoid CD437. J. Biol. Chem. 278, 33422-33435, 2003.