- B.S., St. Xavier's College, 1986
- Ph.D., Carnegie Mellon University, 1994
- Postdoc, Washington University, 1994-2000
- Burroughs Wellcome Fund
- National Institutes of Health
- American Heart Association
We are interested in exploring how cells regulate their survival and death. How does a cell decide whether to survive and cope, or trigger apoptosis in response to different stimuli? If the apoptotic pathway is activated, what is its mechanism and how is it regulated?
Cell death by apoptosis occurs extensively during development and is seen in many pathological conditions such as after stroke or in neurodegenerative diseases. In contrast, the inability of cells to undergo apoptosis is a fundamental hallmark of cancers. Therefore, understanding the mechanisms by which different cells regulate apoptosis has significant therapeutic implications.
We are particularly interested in identifying the unique ways in which different cells control apoptosis. For example, we have found that apoptosis is highly restricted in postmitotic cells such as neurons. An increased restriction of apoptosis is arguably beneficial for the long-term survival of postmitotic cells that have limited regenerative potential and perform critical functions. Interestingly, while neurons and cancer cells are very different by most criteria, there are striking similarities by which apoptosis is restricted in neurons and cancer cells. In contrast, embryonic stem cells are primed to undergo rapid apoptosis in response to DNA damage- an ability that permits for the rapid elimination of damaged cells during embryonic development.
Thus, we focus on identifying mechanisms of apoptosis regulation in neurons, stem cells and cancer cells.
Some Questions Currently Under Investigation:
- What are the mechanisms that allow neurons to survive long-term?
- How does a neuron degenerate its axons yet protect the soma?
- Are there common mechanisms of apoptosis regulation between neurons and cancer cells?
- How is apoptosis controlled in embryonic stem cells
If interested in postdoctoral training in the lab, please send email to: email@example.com.
- Cusack, C.L., V. Swahari, W.H. Henley, J.M. Ramsey, and M. Deshmukh. 2013. Distinct Pathways Mediate Axon Degeneration during Apoptosis and Axon-Specific Pruning. Nat. Commun. 4: 1876. (pdf)
- Gershon, T.R., A.J. Crowther, I. Garcia, R. Annis, H. Yuan, C.R. Miller, A. Tikunov, J. Macdonald, J. Olson, and M. Deshmukh. 2013. Hexokinase-2 mediated aerobic glycolysis is integral to cerebellar neurogenesis and pathogenesis of medulloblastoma. Cancer Metab. 1:2.(pdf) (Preview)
- Dumitru, R., V. Gama, B.M. Fagan, J. J. Bower, L.H. Pevny and M. Deshmukh. 2012. Human Embryonic Stem Cells have Constitutively Active Bax at the Golgi and are Primed to Undergo Rapid Apoptosis. Mol. Cell. 46:573-583. (pdf) (Preview)
- Kole, A.J, V. Swahari, S.M. Hammond, and M. Deshmukh. 2011. miR-29b is Activated During Neuronal Maturation and Targets BH3-only Genes to Restrict Apoptosis. Genes Dev., 25:125-130. (pdf)
- 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. (pdf)
- 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. (pdf) (Featured News Section).
- 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. (pdf) (Featured News Section) (Podcast - Biobytes)
- 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. (pdf) (Featured Comments)
- 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. (pdf) (Featured Comments)
Selected Review Articles
- Kole, A.J., R. P. Annis, and M. Deshmukh. 2013. Mature Neurons: Equipped for Survival. Cell Death & Dis. 4:e689. (pdf)
- Gama, V and M. Deshmukh. 2012 Human embryonic stem cells: Living on the edge. Cell Cycle. 11: 3905-3906. (pdf)
- Wright, K.M. and M. Deshmukh. 2006. Restricting apoptosis for postmitotic cell survival and its relevance to cancer. Cell Cycle. 5: 1616-1620. (pdf)