Departments And Divisions
- Department of Pathology & Cell Biology
- Department of Neurology
- Professor of Pathology and Cell Biology and Neurology (in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain) at CUMC
Our laboratory studies the molecular mechanisms of neuronal degeneration and death, particularly the regulation of caspase activity. Neuronal degeneration and death are the hallmarks of many neurological diseases, including Alzheimer’s Disease, Parkinson’s Disease and stroke, and there is considerable evidence that caspases play a critical role in the progression of these diseases. We have been studying the molecular mechanisms of neuronal death in cultured primary neurons for many years, using various pathologically relevant death stimuli, including beta-amyloid and trophic factor deprivation and have more recently begun studying in vivo rodent models of neuronal death. The rodent stroke model provides an excellent system to move our molecular studies in vivo. This model provides reproducible neuronal death and is also a model of a major human health concern. Our studies in primary neurons have found that different death pathways are initiated by different death stimuli; this is very important from both a mechanistic and a therapeutic standpoint as it provides for the possibility of specific interventions that abrogate the aberrant death signaling but do not interfere with the normal death pathways that are necessary for normal function of the organism. To study death pathways we have developed molecular tools that allow the study of individual members of protein families.
Ongoing projects in the laboratory include:
- Determination of the activation complex of caspase-2. Caspase-2 is a critical regulator of neuronal death.
- Identification and characterization of targets of caspase-2 in neuronal death.
- Studies of the mechanism of caspase-mediated regulation of Bim during beta-amyloid mediated death
- Dose-dependent effects of beta-amyloid on spine density in hippocampal neurons. These studies encompass the physiologic and pathophysiologic functions of beta-amyloid.
- Beta-amyloid regulation of caspase-IAP complexes in neurons and synapses.
- Development and characterization of an in vivo model of beta-amyloid-mediated neuronal death
- Studies of the function of caspase-6 in stroke.
- Determination of the spatial, temporal and cell-type activation of caspases during stroke.
- Establishing therapeutic windows of intervention for stroke. These windows are based on the underlying mechanisms of cell dysfunction and death over the course of stroke.
- MD, PhD, Pharmacology, Medicine, New York Univ School of Medicine
- Internship: Bellevue & New York University Medical Center, NY
- Residency: Neurological Institute of the Columbia-Presbyterian Hospital
- Fellowship: Columbia College of Physicians & Surgeons
Education & Training
William Black Building650 West 168th Street
New York, NY 10032
- (212) 305-3119
- Neural Degeneration and Repair
- Neurobiology of Disease
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.
Jean YY, Ribe EM, Pero ME, Moskalenko M*, Iqbal Z*, Marks LJ*, Greene LA and Troy CM. (2013) Caspase-2 is essential for c-Jun transcriptional activation and Bim induction in neuron death. Biochem J.;455(1):15-25.
Pozueto J, Lefort R, Ribe EM, Troy CM, Arancio O, Shelanski M. (2013) Caspase-2 is required for dendritic spine and behavioural alterations in J20 APP transgenic mice. Nat Commun. 4:1939. doi: 10.1038/ncomms2927.
Ribe EM, Jean YY, Goldstein, RL*, Manzl, C, Stefanis, L, Villunger, A, and Troy, CM. (2012) Neuronal caspase-2 activity and function requires RAIDD, but not PIDD. Biochem J. 444, 591-599.
Tamayev R, Akpan N, ArancioO, Troy CM, D'Adamio L. (2012) “Caspase-9 mediates synaptic plasticity and memory deficits of Danish dementia knock-in mice: caspase-9 inhibition provides therapeutic protection.” Mol Neurodegener. 10.1186/1750-1326-7-60.
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., 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. 31:8894-8904.
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.
Troy, C. M., Akpan, N. and Jean, Y.Y. (2011) “Regulation of Caspases in the Nervous System: Implications for functions in health and disease” Proteases in Health and Disease, ed. E. Di Cera Prog Mol Biol Transl Sci. 99C:265-305.
Ribe Garrido, E, Heidt, L*, Beaubier, N and Troy C. M. (2011) “Molecular Mechanisms of Neuronal Death” Advances in Neurobiology, vol 1, Neurochemical Mechanisms of Disease ed. Blass, JP, pages 17-48.
Siddiq A, Aminova LR, Troy CM, Suh K, Messer Z, Semenza GL, Ratan RR. (2009) Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1 mediates neuroprotection against normoxic oxidative death via HIF- and CREB-independent pathways. J Neurosci. Jul 8;29(27):8828-38.
Ho CC, Rideout HJ, Ribe E, Troy CM, Dauer WT. (2009) The Parkinson disease protein leucine-rich repeat kinase 2 transduces death signals via Fas-associated protein with death domain and caspase-8 in a cellular model of neurodegeneration. J Neurosci. Jan 28;29(4):1011-6.
Troy CM, Ribe EM. (2008) Caspase-2: vestigial remnant or master regulator? Sci Signal. Sep 23;1(38):pe42.
Ribe EM, Serrano-Saiz E, Akpan N, Troy CM. (2008) Mechanisms of neuronal death in disease: defining the models and the players. Biochem J. Oct 15;415(2):165-82. Review.
Biswas SC, Shi Y, Vonsattel JP, Leung CL, Troy CM, Greene LA. (2007) Bim is elevated in Alzheimer's disease neurons and is required for beta-amyloid-induced neuronal apoptosis. J Neurosci. Jan 24;27(4):893-900.
Greene LA, Liu DX, Troy CM, Biswas SC. (2007) Cell cycle molecules define a pathway required for neuron death in development and disease. Biochim Biophys Acta. Apr;1772(4):392-401. Epub 2006 Dec 13. Review.
Davidson, T. J., Harel, S., Arboleda, V. A., Shelanski, M. L., Greene, L. A. and Troy CM. (2004) Highly efficient siRNA delivery to primary mammalian neurons induces microRNA-like effects before mRNA degradation. J. Neurosci 24:10040-10046.