About Our FacultyHarris “Handy” Gelbard, M.D., Ph.D.
Then, earlier this year, Dr. Gelbard was named interim director of the University of Rochester’s Center for Aging and Developmental Biology. He replaced Howard Federoff, MD, PhD, who left late in March to become executive dean of the School of Medicine at Georgetown University. In April of this year, Dr. Gelbard was named the permanent director of the center now known as Neural Development and Disease, renamed in order to embrace a change in both mission and faculty. Dr. Gelbard, an internationally recognized expert on HIV dementia, seems a natural to receive major NIH support for this latest research effort. As principal investigator, he is leading a team of researchers from the University of Rochester and the University of Nebraska Medical Center working to confirm that two new drug classes can protect the brain from HIV-related nerve damage. Their focus: drugs that inhibit glycogen synthase kinase 3 beta (GSK-3b) and mixed lineage kinase type 3 (MLK3.) In the past year, working with an industry partner based in the UK and San Diego, the team has designed and developed a highly promising new set of chemical structures with drug like properties directed at inhibiting MLK3. These compounds are proving to be quite potent and selective against their target and the next step is to partner with biotechnology companies to bring a lead compound to the point where its toxicity and safety profile can be determined. In the interim, they have been broadening the focus of their research to include other diseases where MLK3 is dysregulated, including ototoxicity from aminoglycoside antibiotics, neuropathy from chemotherapy, traumatic brain injury, diabetes, autoimmune disease and cancer. Driving their approach is the realization that antiviral drugs that work
against AIDS do not cure NeuroAIDS. One in five affected patients is now
believed to suffer from HIV-related dementia [HAD] or from a milder form
of neurologic disease that affects both cognitive and motor abilities.
If these studies are successful, human studies will proceed with an existing
MLK3 inhibitor, CEP-1347, developed by Pennsylvania-based biotech firm
Cephalon. Handy Gelbard has been winning research prizes since he was a high school kid in Louisville, KY. He is also a consistent “rainmaker” for the Division of Pediatric Neurology at the University of Rochester, with major support over the years from the Dana Foundation, NIH, NIMH, and the Elizabeth Glaser Foundation. For Gelbard, a career in research was never a given; over the years there has been more than one “path not taken.” As a teenager, he learned from a relative about Northwestern University’s six-year M.D. program, but he found the real impetus to stay in Chicago in the city’s famous blues bars and the magic of blues legend Muddy Waters. (At one time there was a strong possibility that a career as a classical guitarist might trump medicine.) To tell the truth, after a year or two of medical school I wasn’t all that certain that this was where I belonged. I didn’t like the didactic aspect—the sponge like regurgitation of a lot of facts. I was actually much more interested in Anglo-Irish literature and wanted to take my Ph.D. in the work of Joyce and Yeats. My advisors didn’t go for that, so I chose molecular neuropharmacology. Psychopharmacology, I thought, was as close as I was going to get to Joyce’s Ulysses. Then, when I got to the clerkship, things changed. I found I really liked it.” With a career in adult neurology looming and match day coming up, Gelbard realized he was about to make a major mistake. “I decided I loved kids and didn’t like adults,” he says. “It was a gut reaction and I did the unthinkable--I broke my contract, refused to open my match letter.” Fortunately, he found a residency at Northwestern’s Children’s Memorial Hospital, where he had such “a great two years” that he left reluctantly to study child neurology in Boston. At Harvard in 1985, as a junior resident in the Longwood Program, Gelbard found a mentor in Michael Bresnan, MD, “a wonderful guy who combined the complexity of William Butler Yeats with Mr. Rogers—and a great doctor.” The first two years at Harvard, he says, he essentially worked as an adult neurologist—and he missed seeing kids. “Fortunately my child neurology chief resident in my junior year at Children’s Hospital was Nina Tabachnik [now Nina Schor, chair of Pediatrics at UR].” (Soon Nina, an accomplished pianist, and Handy were entertaining friends with their piano/guitar duets.) In his third year at Harvard and now a child neurology chief resident,
Gelbard won a grant from the Dana Foundation for a two-year post-doctoral
fellowship. In 1989, he completed his research on the ontogeny of mammalian
dopamine receptors and their role in schizophrenia at McLean Hospital,
and it was suggested he submit his findings to an international congress
in psychiatry. His paper won first prize. The following year he received
the Child Neurology Young Investigator Award, and shortly thereafter he
was awarded a five-year grant from the NIMH to continue his work. Leon kept trying to recruit me into doing NeuroAIDS research, so with his encouragement I wrote a grant to the Elizabeth Glaser Foundation,” Gelbard says. “I realized that there are no good animal models for schizophrenia research and fairly good models for studying the effects of HIV in the brain. What led me to write the grant was a conversation with Karl Kieburtz, head of experimental therapeutics here. Karl said, ‘I’ve got a bunch of young gay men who are taking AZT for their AIDS and when I give them a dopamine receptor blocker for their nausea they get Parkinsonian symptoms.’ I thought that was really interesting, so I wrote the grant and it was funded. ” In the meantime, Leon Epstein and colleagues at Hopkins and Columbia, encouraged by cohorts of politically motivated patients with AIDS, had put together an effort funded by the Dana Foundation to focus on a translational effort that quickly would move bench research to clinical therapy. “Leon was the principal investigator for that grant,” says Dr. Gelbard. “I was the guy who came up with the molecular targets.” National grants to continue the work soon followed. That work served as the model for the current NIMH grant: Since it is known that the HIV virus itself doesn’t kill neurons, researchers in Rochester and Nebraska will study the molecular targets in the brain that are affected by the deadly by-products produced by infected white blood cells and the enzymes that may have a therapeutic impact on the degenerative process. In particular, biomarkers, proteomics, and neuroimaging, in addition to clinical evaluations, will be used to explore the neuroprotective effect of enzymes in HIV-infected subjects with cognitive impairment. Dr. Gelbard is the epitome of the Renaissance man,” says Dr. Schor, “a cutting-edge biomedical scientist, an outstanding musician, an aficionado of international literature. His most recent work will continue to lead to the identification of novel targets for pharmacotherapy of HIV encephalopathy.” Jonathan Mink, MD, PhD, Unit Chief of Child Neurology said, “Handy has had enormous success with his research program. The implications of his research are likely to extend beyond HIV infection and provide insight into treatment of other conditions with low level inflammation in the brain. His research doesn’t tell the full story. Handy’s persona livens up any interaction with him. His sense of humor and playfulness provides a demonstration that intellectual endeavor and hard work can be accomplished with enthusiasm and enjoyment of all life has to offer. ”
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past two years have been significant for