Research Faculty

Address
650 West 168th Street
BB 12-1210C
New York, NY 10032


Phone: 212-305-3119
Fax: 212-305-0843

cmt2@cumc.columbia.edu
Education and Training
M.D. 1984 NYU School of Medicine
Ph.D. 1984 NYU Graduate School of Arts & Sciences



Affiliations
Anatomy & Cell Biology
Integrated Program
MD-PhD Program
Motor neuron Center
Neurobiology & Behavior
Neurology
Pathobiology
Taub Institute

Collaborations
Michael Shelanski, Lloyd Greene, E. Sander Connolly, Ulrich Hengst
Carol M. Troy, M.D., Ph.D.
Professor of Pathology & Cell Biology, Neurology
Research Summary

The work in my laboratory stems from my long-standing interest in understanding the molecular specificity of death pathways. Throughout the body there is homeostasis of life and death at the cellular level. In disease where death is dysregulated in particular cells there is alteration in the affected cells but not throughout the body. Thus we need to identify specific targets that are altered in the disease state but are not required for normal cellular homeostasis. In our lab we focus on the regulation and function of the caspase family of proteases in the mature nervous system. Best known as the executors of cell death, there is increasing appreciation that some caspases may also have non-apoptotic functions. Individual caspases cleave specific substrates at one or two cleavage sites. Cleavage can result in inactivation of a substrate, a change in the substrates activity, or target the substrate for ubiquitination and degradation. However, caspase cleavage of a substrate on its own does not degrade the cellular proteins. This positions aberrant caspase activity as a potential therapeutic target. We are utilizing novel approaches to inhibit specific family members to dissect the function of each in the normal nervous system and in disease. We utilize in vivo and in vitro models to study both molecular pathways and therapeutic interventions.
Selected Publications

Di Donato, N., Ying Y. Jean,Y.J., A. Murat Maga,A., Krewson, B.D., Shupp, A.B.,Avrutsky, M.I., Roy, A., Collins, S., Olds, C., Willert, R.A., Czaja, A.M.,Johnson, R., Stover, J.A., Gottlieb, S., Bartholdi, D., Rauch, A., Goldstein, A., Boyd-Kyle, V., Aldinger, K.A., Mirzaa, G.M., Nissen, A., Brigatti, K.W., Puffenberger, E.G., Millen, K.J., Strauss, K.A., Dobyns, W.B.,Troy, C.M., and Jinks, R.N. (2016) “Mutations in CRADD Result in Reduced Caspase-2-Mediated Neuronal Apoptosis and Cause Megalencephaly with a Rare Lissencephaly Variant” AJHG 99: 1-13

Troy, C.M. and Shelanski, M.L. (2016) “Caspase-2 and tau: a toxic partnership?”, Nature Medicine, 22:1207-1208.

Pozueta, J., Lefort, R., Ribe, E.M., Troy, C.M., Arancio, O., Shelanski, M.L. (2013) Caspase-2 is required for dendritic spine and behavioral alterations in J20 APP transgenic mice. Nature Communications 4:1939. doi: 10.1038/ncomms2927.

Jean, Y.Y., Ribe, E.M., Pero, M.E., Moskalenko, M., Iqbal, Z., Marks, L.J., Greene, L.A., Troy, C.M. (2013). Caspase-2 is essential for c-Jun transcriptional activation and Bim induction in neuron death” Biochemical J. 455:15-25. (Featured publication).

Vigneswara, V., Akpan, N., Berry, M. Logan, A., Troy, C.M., and Ahmed, Z. (2014) Combined suppression of caspase-2 and -6 protects retinal ganglion cells from apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT signaling pathway. Brain 137(Pt 6): 1656-75.

Baleriola, J., Walker, C.A., Jean, Y.J., Crary, J.F., Troy, C.M., Nagy, P.L., and Hengst, U. (2014) Axonally synthesized ATF4 transmits a neurodegenerative signal across brain regions. Cell, 158:1159-1172.

Blanch, R.J., Ahmed, Z., Akpan, N., Berry, M. Troy, C.M., Scott, R.A.H., and Logan, A. (2014) Caspase-9-Mediates Photoreceptor Apoptosis After Blunt Ocular Trauma. IOVS, 55(10):6350-6357.

Puzzo, D., Privitera, L., Fa’, M., Staniszewski, A., Hashimoto, G., Aziz, F., Sakurai, M., Ribe, E. M., Troy, C.M., Mercken, M., Jung, S. S., Palmeri, A. and Arancio, O. (2011) Endogenous amyloid-β is necessary for hippocampal synaptic plasticity and memory. Ann. Neurol. 69:819-30

Akpan, N., Serrano-Saiz, E., Zacharia, B.E., Otten, M.L., Ducruet, A.F., Snipas, S.J., Liu, W., Velloza, J., Cohen, G., Sosunov, S.A., William H. Frey II, W.F., Guy S. Salvesen, G.S., Connolly Jr, E.S., Troy, C.M. (2011) Intranasal delivery of caspase-9 inhibitor reduces caspase-6-dependent axon/neuron loss and improves neurological function after stroke. J Neurosci. 31:8894-904.

Ribe, E., Jean, Y.Y., Goldstein, R.L., Manzl, C., Stefanis, L. Villunger, A., Troy, C.M. (2012) RAIDD but not PIDD is essential for caspase-2 activity and function in neurons. Biochemical J. 444(3): 591-9.

Davidson, T. J., Harel, S., Arboleda, V. A., Shelanski, M. L., Greene, L. A. and Troy, C.M. (2004) Highly efficient siRNA delivery to primary mammalian neurons induces microRNA-like effects before mRNA degradation. J. Neurosci. 24:10040-10046. (Featured in Faculty of 1000)

Current Projects

A Novel Therapeutic for Diabetic Macular Edema
Principal Investigator Troy
2/02/2013-1/31/2015
Agency: Novo Nordisk
The major goal of this project is to determine the efficacy of a novel therapeutic in models of diabetic macular edema.

Mechanisms and Treatment of CNS Edema
Principal Investigator Troy
7/1/13-6/30/18
Agency: NIH/NINDS
The major goal of this project is to determine the function of proteases in the development of CNS edema.

Honors and Awards

1977-1984 NIH Medical Scientist Training Fellowship

1987-1988 NINDS Clinical Neuroscience Training Fellowship

1988-1989 NIH Individual Postdoctoral Research Fellowship

1989-1994 NIA Clinical Investigator Award
Committees , Council, and Professional Society Memberships

Member NIH-MDCN2 and NOMD Study Sections

Member Editorial Board The Biochemical Journal

Member Editorial Advisory Board of J Clinical Investigation

American Association for the Advancement of Science

The Society for Neuroscience
Keywords

Alzheimer's disease, amyloid protein, ischemia/stroke, apoptosis, cell death, caspase, inhibitor of apoptosis proteins, nerve growth factor, neuron, hippocampal neurons, JUN kinase, brain, synaptic plasticity


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