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

Contact Information

Phone Numbers

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

Faculty Appointments

Patient Care Settings

Neurology, Pediatrics

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

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

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

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

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

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

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Awards

2019
Herman and Gertrude Silver Award on Children, Youth and HIV
Sponsor: The Children's Hospital of Philadelphia

2016
Awardee of the Hilary Koprowski Prize in Neurovirology
Sponsor: Drexel University College of Medicine

2015
Inaugural Awardee of the Translational Research in NeuroVirology Lectureship
Sponsor: International Society for Neurovirology

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

Patent Title: Substituted Pyrrolo [2,3-b] Pyridines as MLK Inhibitors
Patent #: 9,814,704
Issue Date: Nov 14, 2017
Country: United States
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: Substituted Pyrrolo [2,3-B] Pyridines as MLK Inhibitors
Patent #: 9,181,247
Issue Date: Nov 10, 2015
Country: United States
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: Substituted Pyrrolo [2,3-B] Pyridines as MLK Inhibitors
Patent #: 8,877,772
Issue Date: Nov 04, 2014
Country: United States
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: Mixed Lineage Kinase Inhibitors for HIV/AIDS Therapies
Patent #: 10,485,800
Issue Date: Nov 26, 2019
Country: United States
Invented By: Stephen Dewhurst, Harris A Gelbard, Howard E Gendelman

Patent Title: Mixed Lineage Kinase Inhibitors for HIV/AIDS Therapies
Patent #: 2925319
Issue Date: Jan 09, 2019
Country: Europe
Invented By: Stephen Dewhurst, Harris A Gelbard, Howard E Gendelman

Patent Title: Mixed Lineage Kinase Inhibitors for HIV/AIDS Therapies
Patent #: FR2925319
Issue Date: Jan 09, 2019
Country: France
Invented By: Stephen Dewhurst, Harris A Gelbard, Howard E Gendelman

Patent Title: Mixed Lineage Kinase Inhibitors for HIV/AIDS Therapies
Patent #: 602013049719.2
Issue Date: Jan 09, 2019
Country: Germany
Invented By: Stephen Dewhurst, Harris A Gelbard, Howard E Gendelman

Patent Title: Mixed Lineage Kinase Inhibitors for HIV/AIDS Therapies
Patent #: GB2925319
Issue Date: Jan 09, 2019
Country: United Kingdom
Invented By: Stephen Dewhurst, Harris A Gelbard, Howard E Gendelman

Patent Title: Mixed Lineage Kinase Inhibitors for HIV/AIDS Therapies
Patent #: ZL201380060736.1
Issue Date: Aug 10, 2018
Country: China, People's Republic of
Invented By: Stephen Dewhurst, Harris A Gelbard, Howard E Gendelman

Patent Title: Mixed Lineage Kinase Inhibitors and Method of Treatments
Patent #: 9,370,515
Issue Date: Jun 21, 2016
Country: United States
Invented By: Harris A Gelbard, Val S Goodfellow, Thong X Nguyen, Satheesh Babu Ravula

Patent Title: MLK Inhibitors and Methods of Use
Patent #: 2,744,498
Issue Date: Oct 24, 2017
Country: Canada
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: MLK Inhibitors and Methods of Use
Patent #: 5930278
Issue Date: May 13, 2016
Country: Japan
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: MLK Inhibitors and Methods of Use
Patent #: 5873544
Issue Date: Jan 22, 2016
Country: Japan
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: MLK Inhibitors and Methods of Use
Patent #: 2379561
Issue Date: Nov 04, 2015
Country: Europe
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: MLK Inhibitors and Methods of Use
Patent #: FR2379561
Issue Date: Nov 04, 2015
Country: France
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: MLK Inhibitors and Methods of Use
Patent #: 602009034691.1
Issue Date: Nov 04, 2015
Country: Germany
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: MLK Inhibitors and Methods of Use
Patent #: IT2379561
Issue Date: Nov 04, 2015
Country: Italy
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: MLK Inhibitors and Methods of Use
Patent #: ES2379561
Issue Date: Nov 04, 2015
Country: Spain
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: MLK Inhibitors and Methods of Use
Patent #: GB2379561
Issue Date: Nov 04, 2015
Country: United Kingdom
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: MLK Inhibitors and Methods of Use
Patent #: 2009324894
Issue Date: Jul 23, 2015
Country: Australia
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: MLK Inhibitors and Methods of Use
Patent #: 614904
Issue Date: Jun 30, 2015
Country: New Zealand
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: MLK Inhibitors and Methods of Use
Patent #: ZL200980152665.1
Issue Date: Feb 11, 2015
Country: China, People's Republic of
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Torsten Wiemann

Patent Title: Bicyclic Heteroaryl Kinase Inhibitors and Methods of Use
Patent #: 2,800,176
Issue Date: Aug 28, 2018
Country: Canada
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Satheesh Babu Ravula, Torsten Wiemann

Patent Title: Bicyclic Heteroaryl Kinase Inhibitors and Methods of Use
Patent #: 2011258465
Issue Date: Mar 30, 2017
Country: Australia
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Satheesh Babu Ravula, Torsten Wiemann

Patent Title: Bicyclic Heteroaryl Kinase Inhibitors and Methods of Use
Patent #: 6086326
Issue Date: Feb 10, 2017
Country: Japan
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Satheesh Babu Ravula, Torsten Wiemann

Patent Title: Bicyclic Heteroaryl Kinase Inhibitors and Methods of Use
Patent #: ZL201180036376.2
Issue Date: Feb 10, 2016
Country: China, People's Republic of
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Satheesh Babu Ravula, Torsten Wiemann

Patent Title: Bicyclic Heteroaryl Kinase Inhibitors and Methods of Use
Patent #: 603644
Issue Date: Feb 03, 2015
Country: New Zealand
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Satheesh Babu Ravula, Torsten Wiemann

Patent Title: Bicyclic Heteroaryl Kinase Inhibitors and Methods of Use
Patent #: 8,846,909
Issue Date: Sep 30, 2014
Country: United States
Invented By: Stephen Dewhurst, Harris A Gelbard, Val S Goodfellow, Colin J Loweth, Satheesh Babu Ravula, Torsten Wiemann

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Publications

Journal Articles

1/7/2019
Saminathan P, Kevadiya BD, Marker DF, Gendelman HE, Gorantla S, Gelbard HA. "Broad Spectrum Mixed Lineage Kinase Type 3 Inhibition and HIV-1 Persistence in Macrophages." Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology.. 2019 Jan 7; Epub 2019 Jan 07.

10/16/2018
Hammond JW, Qiu WQ, Marker DF, Chamberlain JM, Greaves-Tunnell W, Bellizzi MJ, Lu SM, Gelbard HA. "HIV Tat causes synapse loss in a mouse model of HIV-associated neurocognitive disorder that is independent of the classical complement cascade component C1q." Glia.. 2018 Oct 16; Epub 2018 Oct 16.

5/5/2018
Kiyota T, Machhi J, Lu Y, Dyavarshetty B, Nemati M, Zhang G, Lee Mosley R, Gelbard HA, Gendelman HE. "URMC-099 facilitates amyloid-? clearance in a murine model of Alzheimer's disease." Journal of neuroinflammation.. 2018 May 5; 15(1):137. Epub 2018 May 05.

Books & Chapters

2015
Chapter Title: HAND adjunctive therapies: reversing neuronal injury
Book Title: Encyclopedia of AIDS
Author List: Marker DF, Fitzgerald, T and Gelbard HA
Edited By: Hope, TJ, Stevenson, M, and Richman, D
Published By: Springer Science + Business Media 2015 in New York

2014
Chapter Title: Human immunodeficiency virus
Book Title: Microglia in Health and Disease
Author List: Marker DF, Lu S-M and Gelbard HA
Edited By: Tremblay MÈ and Sierra A
Published By: Science + Business Media 2014 in New York

2012
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 Press 2012 in New York

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