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Last Updated: 5/7/2009
| Mohanish Deshmukh, PhD
Associate Professor |  |
Research Interests
Our laboratory is interested in understanding the fundamental mechanism by which mammalian cells activate the programmed cell death pathway and undergo apoptosis. Defect in the ability of cells to undergo apoptosis is a major factor that leads to carcinogenesis. We are particularly interested in identifying differences in the apoptotic pathway between mitotic and postmitotic cells. To study this, we use a variety of models including primary neurons, cardiomyocytes, myotubes, stem cells and cancer cells.
One major focus in the lab is to understand how caspases become activated during apoptosis. Caspase proteases are the central executors of apoptosis; once activated, caspases cleave specific cellular proteins and induce rapid cell death.
We have identified multiple mechanisms by which caspase activation is strictly inhibited in postmitotic cells. An increased control of apoptosis is particularly beneficial for postmitotic cells as they have limited regenerative potential and the need for long-term survival. Strikingly, we found that these mechanisms are also utilized by cancer cells to evade apoptosis. Ongoing research is focused on studying these and identifying other novel mechanisms of apoptosis control in mammalian cells.
Recent Accomplishments and Honors
Burroughs Wellcome New Investigator Award (2001-2003)
UNC Chapel Hill Teaching Excellence Award (2004)
Editorial Board, Cell Death and Differentiation (Nature Publishing Group) 2007-present
Editorial Board, Oncogene (Nature Publishing Group) 2009- present
Publications
1)Vaughn, A.E and M. Deshmukh. 2008. Glucose Metabolism Inhibits Apoptosis in neurons and Cancer Cells by Redox Inactivation of Cytochrome c. Nat. Cell Biol.. 10:1477-1483.
2) Johnson, C.E.,Y.Y. Huang, A.B. Parrish, M.I. Smith, A.E. Vaughn, K.M. Wright, Q. Zhang, T.V. Dyke, R.J. Wechsler-Reya, S. Kornbluth, and M. Deshmukh. 2007. Differential Apaf-1 Levels Allow Cytochrome c to Induce Apoptosis in Brain Tumors but not in Normal Neural Tissues. Proc. Natl. Acad. Sci. 104:20820-20825. (Featured News Section).
3) Wright, K.M., M.I. Smith, L. Farrag, and M. Deshmukh. 2007. Chromatin Modification of Apaf-1 Restricts the Apoptotic Pathway in Mature Neurons. J. Cell Biol. 179:825-832. (Featured News Section).
4) Smith, M.I. and M. Deshmukh. 2007. ER Stress Induced Apoptosis Requires Bax for Commitment and Apaf-1 for Execution in Primary Neurons. Cell Death & Differ. 14: 1011-1019.
5) Vaughn, A.E. and M. Deshmukh. 2007. Essential Postmitochondrial Function of p53 Uncovered in DNA Damage-Induced Apoptosis in Neurons. Cell Death & Differ. 14: 973-981.
6) Wright, K.M. and M. Deshmukh. 2006. Restricting apoptosis for postmitotic cell survival and its relevance to cancer. Cell Cycle. 5: 1616-1620.
7) Potts, M.B., A.E. Vaughn, H. McDonough, C. Patterson, and M. Deshmukh. 2005. Reduced Apaf-1 levels in cardiomyocytes engage strict regulation of apoptosis by endogenous XIAP. J. Cell Biol. 171:925-930.
8) Wright, K.M., M.W. Linhoff, P.R. Potts, and M. Deshmukh. (2004). Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis. J. Cell Biol. 167:303-313. (Featured Article)
9) Potts, P.R., S. Singh, M. Knezek, C.B. Thompson, and M. Deshmukh. (2003). Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis. J. Cell Biol. 163: 789-799 (Featured News Section)
E-mail: mohanish@med.unc.edu
Telephone: (919) 843-6004
FAX: (919) 966-1844
Address: 7109E Neuroscience Research Building UNC Chapel Hill Chapel Hill, NC
URL: www.neuroscience.unc.edu/faculty_homepages/Deshmukh/?noframe
