Harris A. Gelbard, M.D., Ph.D.

Harris A. Gelbard, M.D., Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 645
Rochester, NY 14642

Fax: (585) 276-1947
Administrative: (585) 273-1749
Office: (585) 273-1473
Lab: (585) 275-7391

Professional Bio

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.

Research Bio

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.

Awards & Honors (National)

National Merit Scholar 1972

Awards & Honors (Local)

Child Neurology Young Investigator Award 1990
Buswell Memorial Fellowship, University of Rochester 1990
First Prize, Wyeth-Ayerst Award or New Psychiatric Research, VIII World Congress of Psychiatry, Athens, Greece 1989
Sigma Xi, Thesis Research 1980

Patents

A Selectively Non-Selective Mixed Lineage Kinase 3 Inhibitor Potentiates the Effectiveness of Antiretroviral Therapy for HIV/AIDS

United States Serial NO.: 14/648,404
Filed Date: November 30, 2013
Title: MIxed Lineage Kinase Inhibitors for HIV/AIDS Therapies
Invented by: Harris Gelbard, Stephen Dewhurst, Howard Gendelman

Recent Journal Articles

Showing the 5 most recent journal articles. 113 available »

2016 Jan 27
Bellizzi MJ, Geathers JS, Allan KC, Gelbard HA. "Platelet-Activating Factor Receptors Mediate Excitatory Postsynaptic Hippocampal Injury in Experimental Autoimmune Encephalomyelitis." The Journal of neuroscience : the official journal of the Society for Neuroscience. 2016 Jan 27; 36(4):1336-46.
2016 Jan
Zhang G, Guo D, Dash PK, AraĆ­nga M, Wiederin JL, Haverland NA, Knibbe-Hollinger J, Martinez-Skinner A, Ciborowski P, Goodfellow VS, Wysocki TA, Wysocki BJ, Poluektova LY, Liu XM, McMillan JM, Gorantla S, Gelbard HA, Gendelman HE. "The mixed lineage kinase-3 inhibitor URMC-099 improves therapeutic outcomes for long-acting antiretroviral therapy." Nanomedicine : nanotechnology, biology, and medicine. 2016 Jan; 12(1):109-22. Epub 2015 Oct 22.
2016
Hammond JW, Lu SM, Gelbard HA. "Corrigendum: Platelet Activating Factor Enhances Synaptic Vesicle Exocytosis Via PKC, Elevated Intracellular Calcium, and Modulation of Synapsin 1 Dynamics and Phosphorylation." Frontiers in cellular neuroscience. 2016 10:113. Epub 2016 May 04.
2015 Apr 1
Puccini JM, Marker DF, Fitzgerald T, Barbieri J, Kim CS, Miller-Rhodes P, Lu SM, Dewhurst S, Gelbard HA. "Leucine-rich repeat kinase 2 modulates neuroinflammation and neurotoxicity in models of human immunodeficiency virus 1-associated neurocognitive disorders." The Journal of neuroscience : the official journal of the Society for Neuroscience. 2015 Apr 1; 35(13):5271-83.
2015
Hammond JW, Lu SM, Gelbard HA. "Platelet Activating Factor Enhances Synaptic Vesicle Exocytosis Via PKC, Elevated Intracellular Calcium, and Modulation of Synapsin 1 Dynamics and Phosphorylation." Frontiers in cellular neuroscience. 2015 9:505. Epub 2016 Jan 08.

Current Appointments

Director - Center for Neural Development & Disease - Primary Administrative
Professor - Department of Neurology, Center for Neural Development & Disease (SMD) - Primary
Professor - Department of Microbiology and Immunology (SMD)
Professor - Department of Neuroscience (SMD)
Professor - Department of Pediatrics (SMD)

Specialties

Neurology with Special Qualifications in Child Neurology - American Board of Psychiatry and Neurology

Education

MD | Medicine | Northwestern Univ Medical Sch1983
PhD | Pharmacology | Northwestern Univ-Chicago Cmp1983
BS | Arts & Sciences | Northwestern Univ-Chicago Cmp1976

Post-Doctoral Training & Residency

Fellowship in Developmental Neuropharmacology at McLean Hospital09/01/1988 - 06/30/1990
Fellowship in Neurology at Children s Hospital09/01/1988 - 06/30/1990
Residency in Neurology at Children s Hospital07/01/1985 - 06/30/1988
Residency in Pediatrics at Children s Memorial Hospital, Northwestern University07/01/1984 - 06/30/1985
Internship in Pediatrics at Children s Memorial Hospital, Northwestern University07/01/1983 - 6/30/1984