Major Research Areas
M Saeed Sheikh, MD, PhD
- Professor of Pharmacology
Research Programs and Affiliations
- Biomedical Sciences Program
- Apoptotic signal transduction and cancer biology.
Cancer Biology and Therapeutics
Defects in regulation of cell death can contribute to a variety of diseases including cancer. Our long-term goals are to elucidate the molecular mechanisms regulating cell death in normal and cancer cells in hope (i) to better understand the process of cancer development and progression and (ii) to develop novel, more efficacious and less toxic anticancer agents. We have identified several novel genes that exhibit (i) oncogenic or tumor suppressor phenotype and (ii) differential expression in response to anticancer drug treatment. We are using state-of-the-art cell and molecular biology, genetic and biochemical approaches to further characterize these genes that are functionally linked to cancer cell growth, death and survival.
He, Q, Luo, X, Huang, Y and Sheikh, MS. Apo2L/TRAIL differentially modulates the apoptotic effects of sulindac and a COX-2 selective non-steroidal anti-inflammatory agent in Bax-deficient cells. Oncogene, 21:6032-6040, 2002.
Luo X, Huang Y and Sheikh MS. Cloning and characterization of a novel gene (PDRG) that is differentially regulated by p53 and ultraviolet radiation. Oncogene, 22:7247-7257, 2003.
He Q, Huang Y and Sheikh MS. Bax deficiency affects caspase 2 activation during ultraviolet radiation-induced apoptosis. Oncogene, 23:1321-1325, 2004.
Sheikh MS and Huang Y. Death receptors as targets of cancer therapeutics. Curr Cancer Drug Targets, 4:97-104, 2004.
He Q, Huang Y and Sheikh MS. Proteasome inhibitor MG132 upregulates death receptor 5 and cooperates with Apo2L/TRAIL to induce apoptosis in Bax-proficient and -deficient cells. Oncogene, 23:2554-2558, 2004.
Corcoran CA, He Q, Huang Y and Sheikh MS. Cyclooxygenase-2 interacts with p53 and interferes with p53-dependent transcription and apoptosis. Oncogene, 24:1634-1640, 2005.
Luo X, He Q, Huang Y and Sheikh MS. Transcriptional upregulation of PUMA modulates endoplasmic reticulum calcium pool depletion-induced apoptosis via Bax activation. Cell Death Differ, 12:1310-1318, 2005.
Corcoran, CA, Luo, X, He, Q, Jiang, C, Huang, Y and Sheikh, MS. Genotoxic and endoplasmic reticulum stresses differentially regulate TRB3 expression. Cancer Biology & Therapy, 4:1063-1067, 2005.
Luo, X, He, Q, Huang Y and Sheikh, MS. Cloning and characterization of a p53 and DNA damage down-regulated gene PIQ that codes for a novel calmodulin-binding IQ motif protein and is upregulated in gastrointestinal cancers. Cancer Research, 65:10725-10733, 2005.
Corcoran CA, Huang Y, Sheikh MS. The regulation of energy generating metabolic pathways by p53. Cancer Biol Ther. 5:1610-1613, 2006.
Huang Y, Sheikh MS. TRAIL death receptors and cancer therapeutics. Toxicol Appl Pharmacol., 24:284-289, 2007.
Rong R, Jiang LY, Sheikh MS, Huang Y. Mitotic kinase Aurora-A phosphorylates RASSF1A and modulates RASSF1A-mediated microtubule interaction and M-phase cell cycle regulation. Oncogene, 26:7700-7708, 2007.
Montalbano J, Jin W, Sheikh MS, Huang Y. RBEL1 is a novel gene that encodes a nucleo-cytoplasmic Ras superfamily GTP-binding protein and is overexpressed in breast cancer. J Biol Chem., 282:37640-37649, 2007.
He Q, Luo X, Jin W, Huang Y, Reddy MVR, Reddy EP, Sheikh MS. Celecoxib and a novel COX-2 inhibitor ON09310 upregulate Death Receptor 5 expression via GADD153/CHOP. Oncogene, 27:2656-2660, 2008.
Corcoran CA, He Q, Ponnusamy S, Ogretmen B, Huang Y and Sheikh MS. Neutral sphingomyelinase-3 (nSMase3) is DNA damage and non-genotoxic stress regulated gene that is deregulated in human malignancies. Mol Cancer Res., 6:795-807, 2008.
Montalbano, J., Lui, K. Sheikh, M.S., Huang, Y. Identification and characterization of RBEL1 subfamily of GTPases in the Ras Superfamily involved in cell growth regulation. J. Biol Chem., 284:18129-18142, 2009.
Shi, J., He, Q., An, J., Sun H, Huang, Y., Sheikh, M.S. Sulindac sulfide differentially induces apoptosis in Smac-proficient and –deficient human colon cancer cells. Mol. Cell. Pharmacol., 1:92-97, 2009.
Corcoran, C.A, Montalbano, J., Sun, H., He, Q., Huang, Y., Sheikh, M.S. Identification and characterization of two novel isoforms of Pirh2 ubiquitin ligase that negatively regulate p53 independent of RING finger domains. J. Biol Chem., 284:21955-21970, 2009.
Jiang L, Luo X, Shi J, Sun H, Sun Q, Sheikh MS, Huang Y. PDRG1, a novel tumor marker for multiple malignancies that is selectively regulated by genotoxic stress. Cancer Biol Ther, 11:567-73, 2011.
Jiang L, Rong R, Sheikh MS, Huang Y. Cullin-4A•DNA damage-binding protein 1 E3 ligase complex targets tumor suppressor RASSF1A for degradation during mitosis. J Biol Chem, 286:6971-8, 2011.
An J, Shi J, He Q, Lui K, Liu Y, Huang Y, Sheikh MS. CHCM1/CHCHD6, novel mitochondrial protein linked to regulation of mitofilin and mitochondrial cristae morphology. J Biol Chem, 287:7411-26, 2012.
Sun H, Jiang L, Luo X, Jin W, He Q, An J, Lui K, Shi J, Rong R, Su W, Lucchesi C, Liu Y, Sheikh MS, Huang Y. Potential tumor-suppressive role of monoglyceride lipase in human colorectal cancer. Oncogene, 32:234-41, 2013.