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

Neurology, Pediatrics

Clinical Interests

Child, Pediatric Neurology; Neurology

Contact Information

Phone Numbers

Appointment: (585) 275-1200

Administrative: (585) 273-1749

Office: (585) 273-1473

Fax: (585) 276-1947

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 Neurotherapeutics Discovery (CND) and a Professor of Neurology, Pediatrics, Neuroscience and Microbiology & Immunology at the University of Rochester Medical Center. The CND grew out of the Center for Neural Development and Disease (CNDD), which was renamed from its original origin as the Center for Aging and Developmental Biology (CADB), started by the first Director, Howard J. Federoff. In 2007, Dr. Federoff left URMC and at his suggestion, I became the interim director of the CADB, until it was renamed the CNDD the following year to reflect our unswerving commitment to understand neurologic disease in the context of development. As we have evolved, it became apparent that our core strengths were reflected in our collective mission to not only understand development of the nervous system, but to create new therapies to fix disease at a molecular level. Thus, we have finally arrived at a collective identity known as the CND.
I came to the URMC as a postdoctoral fellow in 1989, and stayed as a physician-scientist. While I started my career as a developmental neurobiologist and pediatric neurologist interested in how dopamine was affected during early brain injury, I shifted my research focus radically nearly 25 years ago in an attempt to repurpose already FDA-approved medicines for the treatment of neurologic disease associated with HIV-1 infection. Frustrated by the realization that our progress was incremental, I lead an interdisciplinary, international team to develop a new class of small molecule therapeutics that target mixed lineage kinases. Our efforts evolved to the point where we have secured three internationally prosecuted composition of matter and methods of use patents for these compounds, and we are more than halfway through investigational new drug-enabling studies for our development compound, URMC-099. These experiences have placed me at an intersection between preclinical laboratory efforts to understand relationships between immune effector cells in the central nervous system and synaptic repair during neuroinflammation, and the many steps necessary to bring small molecule technologies into existence as potential drugs. Thus, I feel privileged as the Director that the CND represents a unique opportunity for our investigators to ask questions about disease and answer them with new pathways to therapy.

Research

Our lab's interests have been shaped by trying to understand how HIV-1 can disrupt normal cognitive functions by altering homeostasis between microglia and synaptic networks. Much like experience-driven synaptic plasticity, this has been and continues to be a work in progress influenced by our trainees' interests, the experimental approaches they have formulated to help us understand how innate immunity can both shape and repair the central nervous system (CNS), and the novel results that they have produced. Our laboratory has no single technique that has influenced our approach to understanding how the virus can disrupt normal synaptic transmission, although we favor methods that allow us to visualize our data, preferably in real time. Because my training as a molecular neuropharmacologist has emphasized understanding how signaling pathways can be disrupted during disease and whether these pathways can be restored to a new homeostatic relationship between the immune system and vulnerable synaptic networks, we have focused on kinase signaling that controls neuroinflammation. Our efforts to both understand how HIV-1 infection in the CNS disrupts this type of kinase signaling and create small molecule inhibitors of the mixed lineage kinases (MLKs) so that we could test this as a therapeutic approach to HIV-1 associated neurocognitive disorders (HAND), led us to the current point of successfully developing a new class of drugs that inhibit MLKs in macrophages/microglia and neurons to restore homeostasis. This has been extraordinarily serendipitous for us, because we have realized that loss of homeostasis between an end organ target cell, whether it is a neuron, cardiomyocyte or hepatocyte can be restored, with disease-modifying outcomes in HAND, MS (using an EAE model employed by Dr. Matt Bellizzi in our lab), post-operative cognitive dysfunction (POCD; in collaboration with Dr. Niccolo Terrando at Duke University), Alzheimer's disease (with Dr. Gendelman at UNMC and Drs. Todd Krauss and Brad Nilsson at UR), non-alcoholic steatohepatitis (NASH; in collaboration with Dr. Samar Ibrahim at Mayo Clinic) and ischemia-reperfusion injuries (MI; in collaboration with Dr. Burns Blaxall at the Cincinnati Children's Hospital). Lastly, and perhaps most importantly to our lab's core mission, in work we have done with Dr. Howard Gendelman (UNMC) and Drs. Maggirwar and Dewhurst here at URMC, we have discovered that the combination of nanoformulated antiretroviral therapy (nanoART, developed by Dr. Gendelman) for HIV-1 and our lead compound for inhibition of MLKs, URMC-099, can reverse HIV-1 blockade of autophagy in persistently infected macrophages, allowing nanoART to effectively eliminate HIV-1 without inflammation and bystander cellular damage. This has led to additional approaches to new therapies both for HAND and eradication of persistent HIV-1 infection.
For trainees at the pre- and postdoctoral level, we are currently investigating the role of the transcription factor, Mafb, using a combination of optogenetic and CRISPR/Cas9 techniques, in regulating a neuroinflammatory response during HIV-1 infection of the CNS; the role of soluble intercellular adhesion molecule type 5 (sICAM-5) as a biomarker for synaptodendritic damage during HAND; dysregulation of complement signaling during HAND and MS; and therapeutic strategies to repair hippocampal and cortical synaptic injury during MS that remain resistant to current immunomodulatory therapies. Additional projects related to our collaborations with other investigators described above are also ongoing.

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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