Endogenous neurogenesis in stroke

Current treatment strategies for stroke primarily focus on reducing the size of ischemic damage and on rescuing dying cells early after occurrence. Treatments, such as the use of thrombolytic agents, are often limited by a narrow therapeutic time window. Cerebral ischemia can also activate endogenous repair processes. Our goal is to understand the role of neural progenitor cells (NPCs) and reactive astrocytes that acquire stem cell properties during brain injury recovery. The long-term goal of our research is to determine the molecular basis of SVZ/SGZ or local neurogenesis at the injury sites and to identify novel therapeutic strategies for expanding the treatment window for brain injuries such as stroke. Our laboratory utilizes combined strategies such as inducible cell-type specific or activity-dependent gene modification in animal models and pharmacological manipulations of molecular pathways to gain a comprehensive understanding of key molecular pathways that contribute to CNS regeneration.

Cell replacement therapy in Parkinson's Disease

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. Clinical symptoms of PD do not manifest until 60-80% of DA neurons have been affected. This presents a challenge for the treatment of the disease since when patient is diagnosed the disease has progressed to a significant pathological degree.  Parkinson’s disease has been an attractive target for cell replacement therapy because the main pathology underlying PD symptoms is a progressive degeneration of mesencephalic dopamine neurons. Replacement of dopaminergic neurons and reinnervation of the target area (striatum) have been the major goals in PD cell replacement therapy. However, the survival rate of the transplanted cells is low. Research projects in our laboratory include studying the role of apoptotic process in neuronal death in PD. Similar processes might also be responsible for the death of transplanted cells. We have generated modified ES cells in which certain genes will be specifically inactivated upon differentiation to dopaminergic neurons. By examining the survival and efficacy of transplantation of these modified ES cells, it will be possible to identify genetic pathways that will improve the survival and functional outcome of cell transplantation in PD. Our long term goal is to develop pharmacological treatments that modify these critical pathways that will result in improved survival of transplanted cells and better functional recovery in PD treatment.