Current Research and Scholarly Interests
Clinical interests include Alzheimer’s disease and Huntington’s disease and the development of effective therapeutics for these disorders.
Our research group is focused on the discovery of cellular signaling mechanisms that serve as a basis for the development of novel therapeutic approaches for Alzheimer’s disease, Huntington’s disease and other neurological disorders. In our Neurotrophin Program, we have pioneered the development of small molecule ligands targeted to neurotrophin receptors to promote novel signaling mechanisms. Small molecule-induced activation of these mechanisms demonstrates therapeutic efficacy in models of Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, spinal cord injury, amyotrophic lateral sclerosis (ALS), HIV dementia and other areas. These novel compounds also promote neurogenesis from stem cells.
In our Protein Tyrosine Phosphatase Receptor Program we have elucidated the role of protein tyrosine phosphatase (PTP) receptors in the nervous system by focusing on LAR, a prototype PTP receptor that we discovered to be expressed in the nervous system. Our studies demonstrated the first CNS and PNS phenotypes in a PTP receptor mutant mouse, discovered PTP extracellular domains responsible for their potent neurite promoting effects, found that LAR associates with Trk neurotrophin receptors to regulate their activity, showed that down regulating LAR promotes stem cell proliferation and stimulates hippocampal neurogenesis, and developed a novel approach for down regulating PTP activity. This work reveals additional candidate therapeutic targets for small molecule development.