Carol M. Troy, MD, PhD

Our laboratory studies the molecular mechanisms of neuronal degeneration and death, particularly the regulation of caspase activity. A central question of our work is the function of the individual members of this multi-membered family in the nervous system. We seek to understand the cell-specific apoptotic and non-apoptotic signaling of the individual caspases in development and disease in the nervous system. We utilize mouse models and employ genetic and pharmacologic approaches to elucidate mechanisms.

We have identified non-apoptotic activation of endothelial caspase-9 as a critical mediator of edema, inflammation and cell death in a mouse model of retinal edema (Avrutsky et al., 2020). Prior work in our lab identified caspase-9 as the initial caspase activated in rodent models of cerebral ischemia. In all of these models there is neurovascular dysfunction and on-going studies are addressing how endothelial caspase-9 is signaling to the multiple cell types of the neurovascular unit, including microglia, astroctyes and neurons. Since there is often overlap of developmental pathways with those activated in disease we utilized the postnatal establishment of the mature retinal vasculature to examine potential developmental functions of endothelial caspases in vascular development and have found that endothelial caspase-8 plays a critical role in vessel outgrowth and pruning from postnatal days 6-10.

Current projects include 1) determining how endothelial caspase-9 regulates inflammation; 2) elucidating the critical substrates of endothelial caspase-9 in retinal edema; 3) establishing how endothelial caspase-8 regulates normal retinal angiogenesis; 4) developing and characterizing a mouse model of intracerebral hemorrhage using focused ultrasound and lipid microbubbles (in collaboration with the Konafagou lab); 5) determining the role of cradd, the death adaptor of caspase-2 in cognitive development.