I am the Director of the Center for Neural Development and Disease and Professor of Neurology, Pediatrics and Microbiology & Immunology at the University of Rochester Medical Center. I have a strong interest in interdisciplinary training for graduate students and have emphasized ongoing collaborations with faculty from Microbiology and Immunology that have a particular interest in HIV-1 at the University of Rochester, sharing undergraduate, predoctoral and postdoctoral trainees over the past 25 years. With over 25 years of experience as a molecular neuropharmacologist, I have worked primarily with experimental models of neuroAIDS and HIV-1 induced neuroinflammation since 1992. As the leader of the NeuroAIDS Scientific Working Group in the UR's NIH-funded Center for AIDS Research (CFAR), our team has worked to develop new therapies for HIV-associated neurocognitive disorders (HAND) for nearly a decade.
During this time, we have extended our studies to post-operative cognitive decline (POCD) and multiple sclerosis (MS), neuroinflammatory conditions that have overlapping signaling mechanisms with HAND. Our major research goal is to develop protective approaches by targeting mixed lineage kinase (MLK3) and leucine rich repeat kinase 2 (LRRK2), upstream kinases that regulate neuroinflammation and neuronal function/fate through effects on downstream kinases that include Jun N-terminal kinase (JNK). During the last two cycles of PO1 MH64570, we have developed novel small molecules that efficaciously inhibit MLK3 and LRRK2, and we have tested these new inhibitors in in vitro and in vivo models for HAND, with the goal of filing an investigational new drug (IND) application with the FDA. We are presently on track with this goal, after obtaining two patents related to both composition of matter and methods of use for our lead MLK3 inhibitor (US 8,846,909 B2, US 8,877,772, Patents pending in Canada, Europe, New Zealand (Awarded, 2015), Australia, China (Awarded, 2015), and Japan; PCT application: PCT/US2009/065878 and PCT/US2011/037758).
Our lead compound, URMC-099 is currently undergoing safety and preclinical toxicology studies spearheaded by a Rochester-based new biotech company, WavoDyne Therapeutics, Inc. I lead the scientific advisory board of WavoDyne to prepare for an IND in 2015 for a first-in-class adjunctive therapy for HAND with URMC-099. Our laboratory has a preclinical focus on neuroinflammation and synaptic plasticity with an overarching translational goal of restoring synaptic plasticity (the basis for learning and memory) in neuroinflammatory conditions. This confluence of research interests, laboratory techniques, and relationships with long-term collaborators at UNMC and more recent collaborators in industry (Califia Bio, Inc and WavoDyne Therapeutics, Inc.), along with a very exciting research program developed in Dr. Maggirwar's laboratory that focuses on the role of platelets in facilitating recruitment of infected leukocytes into the CNS during acute and chronic stages of HIV-1 infection as well as mechanisms by which platelets "push" HIV-infected leukocytes through the blood-brain barrier suggests a very novel use of our brain-penetrant MLK3 inhibitor, URMC-099.