Arun K. Rishi
Arun K. Rishi, Ph.D.
4646 John R.
John D. Dingell VA Medical Center
Detroit, MI 48201
- Apoptosis signaling by CARP-1.
Cell growth inhibition by CARP-1-inducing Small molecule(s).
Research in our laboratory focuses on elucidating pathways regulating cellular growth and apoptosis. By utilizing a functional gene-knockout approach, we identified and characterized a novel, apoptosis inducing protein termed CARP-1/CCAR1. CARP-1 regulates cell-growth inhibitory and apoptosis-promoting signals by chemotherapy drug adriamycin, as well as a novel class of apoptosis-inducing adamantyl retinoids. CARP-1 also regulates epidermal growth factor (EGFR)-dependent signaling events since inhibition of EGFR results in increased levels of CARP-1 and apoptosis. CARP-1 is a tyrosine as 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 interacting proteins 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, TAZ, and p21Rac-1 proteins. Our data from biopsies of human breast and colon cancers, and lymphomas suggest an inverse correlation of CARP-1 expression with tumor grades, indicating a potential tumor suppressor property of CARP-1. Administration of peptide(s) derived from CARP-1 suppresses growth of human breast cancer and lymphoma cells in vitro, as well as of tumor xenografts. The molecular complexity of cancers and therapy-associated side effects often limit effectiveness of many therapies, and warrant development of new agents for specific molecular targets, while minimizing off-target effects. Our long-term goal is to develop mechanism-based novel, safer and effective targeted anti-cancer therapies.
Cheriyan, V.T., Muthu, M., Sekhar, S., Patel, K., Larsen, S.D., Rajeswaran, W., Polin, L. A., Levi, E., Singh, M., Rishi, A.K. CARP-1 functional mimetics are novel inhibitors of drug-resistant triple-negative breast cancers. Oncotarget (in Press).
Muthu, M., Cheriyan, V.T., Rishi, A.K. CARP-1/CCAR1: A biphasic regulator of cancer cell growth and apoptosis. Oncotarget 2015;6:6499-510.
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. 2015;11:1608-27.
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 2014;9:e102567.
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 2014;9:e89146.
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 2013;8:e66733.
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. 2011;286:38000-17.
Education and Training:
MSc Biochemistry: University College of London, University of London, United Kingdom
PhD Molecular Biology: Imperial College of Science, Technology, and Medicine, University of London, UK
Post-Doc: Massachusetts Institute of Technology, Cambridge, Massachusetts
Post-Doc: Brigham & Womens Hospital, Harvard, Cambridge, Massachusetts
Cancer Biology Courses Taught:
CB7300 Special Topics - F31 Grant Writing Course
CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling (Course Director)