Dr. Lagacé’s lab uses a variety of molecular, cellular, histochemical and behavioral techniques to identify the mechanisms that produce new neurons in the adult brain and to determine their functional role in the healthy and pathological brain. For example, work in the lab is delineating the molecular mechanisms that regulate survival of adult-generated neurons and the crosstalk between autophagy and apoptosis in regulating survival. They are also examining the role of Presenilin proteins in adult neurogenesis in their work related to Alzheimer’s disease. These studies are providing insights into the basic biological processes that underlie the regulation of the potentially powerful adult generated neuron. This work complements behavioral studies that are elucidating the functional role of adult neurogenesis in normal physiology, as well as optimizing functional recovery in animal models of human disease. For example, as members of the Canadian Partnership for Stroke Recovery, a large number of studies in the lab are using novel models to examine whether the pronounced birth of new cells post stroke are functionally important in recovery and optimize regeneration and recovery of function during stroke recovery. .
The discovery of adult neurogenesis and the advances of stem cell research have immense clinical implications for a wide variety of human pathologic conditions. The benefits of this research include the potential for novel therapeutics targeted at cellular replacement or repair, as well as hope for neuroprotective strategies aimed at maintaining cellular plasticity. In order to accomplish these clinical goals, we are interested in defining the molecular mechanisms that underlie stem cell proliferation, neuronal differentiation, and ultimately integration into existing neural and synaptic circuits.
Many physiological and pathological activities have been identified to alter the number of dividing cells in the adult brain, yet the factors that produce neuronal differentiation and ultimately survival of new neurons remain largely unknown. We use a variety of molecular, cellular, histochemical, and behavioral techniques to identify and elucidate novel mediators of adult neurogenesis. For example, we previously identified that cyclin-dependent kinase 5 (Cdk5) regulates the maturation of adult-generated neurons using multiple transgenic mouse models and an in vivo viral-mediated knockout approach. Current work in the lab is delineating the molecular mechanisms that regulate the activity and downstream effects of Cdk5 in neurogenesis. We are also interested the functional role of adult neurogenesis in normal physiology, as well as optimizing functional recovery in animal models closely resembling human disease. For example, in models of stroke there is a pronounced birth of new cells and we are interested in determining where these cells arise and whether they are functionally important in behavioral recovery. With an eye on potential clinical applications, these lines of investigation will afford insights into basic biological processes that underlie the regulation of the potentially powerful adult generated neuron.
Dr. Lagacé’s research is funded by the Canadian Institute for Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), Ontario Brain Institute (OBI), and the Canadian Partnership for Stroke Recovery (CPSR).