Professor, Skirball Institute of Biomolecular Medicine, NYU School of Medicine
My laboratory is interested in the mechanism of trophic factors, which are secreted proteins required for neuronal growth, survival and differentiation in the development of the nervous system. The neurotrophins, NGF and BDNF, also play a central role in learning and memory, anxiety, pain and mood disorders. Neurotrophins use two different receptors, the Trk receptor tyrosine kinase and the p75 receptor, to nourish neurons, guide axons to form proper connections and determine life-death cell decisions. After PhD research in biochemistry at UCLA and postdoctoral research at Columbia Medical Center, I was involved in the cloning of the first NGF receptor, referred to as the p75 neurotrophin receptor. At Cornell Medical School, I was involved in how the TrkA tyrosine kinase and the p75 receptor were involved in creating high affinity binding sites for NGF.
In the adult nervous system, BDNF is a principal activity-dependent gene that is directly linked to increased synaptic strength, neurogenesis, axonal branching and remodeling of neuronal connections. Deficits in BDNF levels, contribute to a variety of conditions, including memory impairment, depression, obesity and neurological disorders, such as Alzheimer’s and Huntington’s diseases. The primary goals are to define the downstream steps in receptor signaling by trophic factors and to understand how specificity is generated by cell-cell communication in the nervous system. Alterations in the levels of neurotrophins are highly influenced by neuronal activity. We have discovered a mechanism whereby activity, such as physical exercise, increases BDNF levels. In addition, transactivation of Trk receptors by small molecule ligands of G protein-coupled receptors also offers a strategy for enhancing neurotrophic effects in the absence of neurotrophins. These mechanistic studies are fundamental to future treatments of psychiatric and neurodegenerative diseases.
I am a Fellow of the AAAS, a recipient of the Zenith Award, the Jacob Javits Neuroscience Investigator Award, the Guggenheim Fellowship, the Julius Axelrod Prize and I served as President of the Society for Neuroscience in 2012.