The lab is interested in two main problems in molecular neuroscience: the molecular biology of learning and memory, and the genetic mechanisms underlying neurological disorders. The approach we use involves the manipulation of gene expression in a region-specific manner using viral gene delivery.
Learning and Memory
Identification of putative learning and memory genes both in the young and aged rat using Microarrays constitute our starting tools to study the neurobiology of learning and memory going from genes to behavior. Our ultimate goal is to understand the molecular rules that govern memory formation and plasticity in the CNS both early in life and with aging. The first goal in the lab is to screen the genes that were identified in the array experiments at the functional level. Towards that end, we are using recombinant adeno-associated virus (rAAV) as a gene delivery system to overexpress or knock-down function of these candidate genes in the brain in a region-specific manner and examine the resulting phenotypes using well established behavioral tests. Viral gene delivery is a fast way to screen for this long list of genes in a feasible time frame. It takes approximately a couple of months to generate “somatic” transgenic animals from the purification of the virus to expression of the virus in the desired brain region of the animal, to testing the behavior. This technology can also be used to manipulate the expression of one gene or several genes in combination, so the relationships between the different genes in a pathway can be assessed in vivo.
Our interest in neurodegenerative disorders has been focused on Parkinson's disease (PD). We have two main areas of research in PD:
Gene Therapy Approaches for the Treatment of PD
We are investigating trophic factors and the rate limiting enzymes for the production of dopamine as potential therapeutic agents.
Characterization of Viral Vectors for the Regulation of Transgene Expression.
We are developing vectors that will allow regulated expression of therapeutic genes. We are screening a number of constructs based on the Tetracycline regulation system, as well as other novel approaches.