David Park, PhD
Affiliate Investigator, Neuroscience, Ottawa Hospital Research Institute
Professor Park's research interests are in the area of delineating the signalling pathways which control neuronal death. Apoptic cell death was initially defined by characteristic morphological changes. However, a rapidly growing body of work has developed a more biochemical view of apoptosis, and tremendous progress has been made in characterization of the molecules that regulate this process. The classical biochemical view of apoptotic regulation is that a wide variety of apoptotic stimuli initiate death by activating a wide range of upstream effector signalling events. These events are somehow integrated to control the commitment point of cell death via activation of the caspases. Once the caspases are activated, they initiate a series of downstream events which irreversibly lead to the phenotype of death. Analysis of cell death in various systems, including his own work in neurons, has revealed several key points about apoptotic pathways: 1) there are certain conserved classes of molecules that regulate death in nearly all apoptotic paradigms. These include the mammalian homologues of the C. elegans cell death genes Ced 3, 4, and 9. 2) Apoptosis is regulated by causally related, multistep signalling events that culminate in cell destruction. 3) Different initiating apoptotiic stimuli may trigger distinct pathways composed of conserved cell death components (Ced genes and their homologues) and diverse upstream signalling elements that depend on cellular context.The goal of Professor Park's research is to:
- Understand the signalling molecules involved in the control of apoptotic death in specific in vitro models of neuronal death induced by trophic factor deprivation (developmental model of death), DNA damage (important for brain related pathologies) and B-amyloid (Alzheimer's model). Some of the particular signalling events of interest are cell cycle related molecules (CDKs, Rb, E2F), caspases and stress activated c-Jun kindase.
- Identify the relevant apoptotic regulators in animal models of brain pathology (in particular, stroke).
In understanding the control pathways which regulate apoptosis, it is hoped that one can not only gain an appreciation for an important basis biological process but also device therapeutic strategies to treat neuronal diseases.