Research in my laboratory has been aimed at understanding how neurons differentiate into dopamine neurons during development of the brain and how that information may be useful for the treatment of neurodegenerative diseases such as Parkinson's disease (PD). A major goal of our studies has been defining the key fate determinant genes and lineage stages in the development of human dopamine neurons. Our hope is that an understanding of those mechanisms that first direct expression of neurotransmitter genes during differentiation will provide a molecular blueprint that can be used to intentionally target the differentiation of cells such as human embryonic stem or adult induced pluripotent cells toward that phenotype. Using an approach that combines cell culture and animal models of PD, our aim is to induce dopaminergic traits in human stem cells and devise ways to amplify and purify prospective human dopamine neurons for the development of cell-based therapies in PD, for future studies of PD in the dish and for the production of a high throughput screen for PD drug discovery.

Also, in the last few years, we have begun to explore a neuroprotective strategy to treat PD disease. Using gene microarray analysis, candidate genes isolated from PD-spared ventral tegmental neurons of the midbrain have been analyzed for their neuroptotective properties on PD-susceptible substantia nigra neurons. These studies have revealed a number of interesting molecules, including the glycoprotein Gremlin-1, which has the capacity to rescue dopamine neurons from neurotoxic damage in vitro and in vivo.

In addition, recently we have expanded our studies on stem cells in the lab to explore their potential use as a treatment for stroke, which remains the leading cause of disability and the third leading cause of death in the US. Our work and that of others shows that IV injection of bone marrow stem cells significantly protects brain structure and reverses sensory and motor deficits after experimental stroke. In an effort to understand the mechanism of action through which stem cells mediate their striking effects, we are currently studying the molecular correlates that accompany stem cell-induced recovery in rat and tissue culture models of stroke.