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Harris Andrew Gelbard, M.D., Ph.D.

Neurology, Pediatrics

Clinical Interests

Child, Pediatric Neurology Neurology

Contact Information

Phone Numbers

Administrative: (585) 273-1749

Appointment: (585) 275-1200

Fax: (585) 276-1947

Office: (585) 273-1473

URMFGA member of the University of Rochester Medical Faculty Group

groupAn Accountable Health Partner

assignmentAccepting New Patients

Biography

Professional Background

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

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.

Credentials

Faculty Appointments

Specialties

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

Education

1976
BS | Northwestern Univ-Chicago Cmp
Arts & Sciences

1983
MD | Northwestern Univ Medical Sch
Medicine

1983
PhD | Northwestern Univ-Chicago Cmp
Pharmacology

Post-doctoral Training & Residency

07/01/1984 - 06/30/1985
Residency in Pediatrics at Children s Memorial Hospital, Northwestern University

07/01/1985 - 06/30/1988
Residency in Neurology at Children s Hospital

09/01/1988 - 06/30/1990
Fellowship in Developmental Neuropharmacology at McLean Hospital

09/01/1988 - 06/30/1990
Fellowship in Neurology at Children s Hospital

07/01/1983 - 6/30/1984
Internship in Pediatrics at Children s Memorial Hospital, Northwestern University

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Awards

1990
Child Neurology Young Investigator Award

1990
Buswell Memorial Fellowship, University of Rochester

1989
First Prize, Wyeth-Ayerst Award or New Psychiatric Research, VIII World Congress of Psychiatry, Athens, Greece

1980
Sigma Xi, Thesis Research

1972
National Merit Scholar

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Patents

Title: Mixed Lineage Kinase Inhibitors and Method of Treatments
U.S. Serial #: 15/134,202
Filed: Apr 20, 2016
Invented By: HarrisGelbard, ValGoodfellow, ThongNguyen, Satheesh BabuRavula

Title: Mixed Lineage Kinase Inhibitors and Method of Treatments
U.S. Serial #: 14/201,673
Filed: Mar 07, 2014
Invented By: HarrisGelbard, ValGoodfellow, ThongNguyen, Satheesh BabuRavula

Title: Mixed Lineage Kinase Inhibitors and Method of Treatments
U.S. Serial #:
Filed: Mar 07, 2014
Invented By: HarrisGelbard, ValGoodfellow, ThongNguyen, Satheesh BabuRavula

Title: MIxed Lineage Kinase Inhibitors for HIV/AIDS Therapies
U.S. Serial #: 14/648,404
Filed: Nov 30, 2013
Invented By: StephenDewhurst, HarrisGelbard, HowardGendelman

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Publications

Journal Articles

1/27/2016
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.

1/2016
Zhang G, Guo D, Dash PK, Araínga 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 0; 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.

Books & Chapters

2011
Chapter Title: Development of Adjunctive Therapies for the Neurological Manifestations of AIDS: HAND and Painful Neuropathy
Book Title: The Neurology of AIDS
Author List: Gelbard, H.A. and Lipton, S.A.
Edited By: Everall, Fox, Gelbard, Grant, Lipton, Swindells and Gendelman
Published By: Oxford Press2011 in New York

2008
Chapter Title: Neuroimmunology and the Pathogenesis of HIV-1 Encephalitis in the HAART Era: Implications for Neuroprotective Treatment.
Book Title: The Spectrum of Neuro-AIDS Disorders: Pathophysiology, Diagnosis, and Treatment.
Author List: Perry, S.W. and Gelbard, H.A.
Edited By: In Goodkin, Shapshak, and Verma (eds.)
Published By: ASM Press2008 in New York

2008
Chapter Title: Infectious agents in neurodegenerative disease
Book Title: Encyclopedia of Neuroscience
Author List: Bellizzi, M.J and Gelbard, H.A.
Edited By: In Larry R. Squire (Editor-in-Chief)
Published By: Academic Press2008 in Oxford

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