Two University of Miami Miller School of Medicine doctoral candidates, Zachary Silver and Yi Zhu, are the recipients of the 2019 Louis J. Elsas Research Award in Biochemical Genetics for their innovative genetic research into neurodegenerative disease and HIV.
Sixteen candidates applied for the honor this year, which remembers the legacy and contributions of the late Louis J. “Skip” Elsas, M.D., a geneticist who became the first director of the Dr. John T. Macdonald Foundation Center for Medical Genetics, now known as the Dr. John T. Macdonald Foundation Department of Human Genetics.
The award, which provides $2,500 for each recipient, supports outstanding medical students, graduate students, and postdoctoral fellows who are performing research relevant to biochemical genetics, biochemistry, genetics, genomics, statistical genetics, or genetic epidemiology.
Ph.D. candidate Yi Zhu, M.D.
Yi Zhu, M.D., a sixth-year Ph.D. student in the Graduate Program of Molecular and Cellular Pharmacology, was nominated by R. Grace Zhai, Ph.D., associate professor in the Department of Molecular and Cellular Pharmacology, whose research focuses on the genetic and biochemical mechanisms of neurological diseases.
“I am very grateful for this honor,” said Dr. Zhu, who was born in China. “I want to thank my mentor for nominating me and for the training she provides me. I also want to thank all of my lab members who collaborate with me.”
Dr. Zhu has devoted himself to investigating the genetic causes of neurological disorders such as Huntington’s disease, which currently has no cure. Using a Drosophila melanogaster (fruit fly) model, Dr. Zhu is specifically interested in understanding how genetic mutations lead to neurodegeneration and the molecular mechanism underlying the neurotoxicity of the disease.
“We need to understand the basic biology and what’s causing it before we can seek any treatment,” he said.
“Dr. Zhu has actively participated in numerous projects in my lab and sought collaborations within and outside the medical school,” Dr. Zhai said. “He is highly motivated in science and an excellent multitasker—sometimes he is pushing forward up to 10 projects simultaneously where he is achieving significant insights.”
Dr. Zhu earned his medical degree in China and then did his academic training at the Zhongshan Ophthalmic Center at Sun Yat-sen University, where he focused his research on identifying genetic mutations in congenital ophthalmic diseases. He came to UM to further pursue his interest in genetic disorders.
Many awards, including the Lois Pope LIFE Foundation Development Award in 2015, Lois Pope LIFE Foundation Research Award in 2017, and Medical Faculty Association Travel Awards in 2017, have recognized Dr. Zhu’s achievement in research.
His research publications have gathered significant interest in the neuroscience field, and he has already published 10 papers as co-first author, or co-author, and has another four under consideration. He actively participates in conference meetings and has given two oral presentations to share his research advances.
M.D. candidate Zachary Silver, Ph.D.
Zachary Silver, Ph.D., is an M.D. candidate in the Medical Scientist Training Program at the Miller School of Medicine. In July 2019, he successfully defended his thesis after completing his third year of dedicated research in the laboratory of Ronald C. Desrosiers, Ph.D., professor of pathology and director of research faculty development. The Desrosiers laboratory studies the molecular aspects of HIV infection and is working toward a vaccine and cure for HIV.
“I felt blessed and grateful when I heard I had been nominated,” said Dr. Silver. “As scientists, we are constantly plagued by failures, from experiments to rejection of our papers and grants. It is easy to let it weigh on you. Receiving recognition, or a little positive reinforcement, goes a long way in helping you remember that failure is just part of the journey toward success.”
Dr. Silver started pursuing his M.D. /Ph.D. a few years after graduating from Tufts University with a Bachelor of Science in biology.
After doing undergraduate research on the tick-borne infection babesiosis and going to India as a Fulbright Scholar studying diarrheal disease in children, Dr. Silver came to UM with an interest in joining the fight against HIV through molecular and genetic studies. Miami-Dade County has the highest number of newly infected HIV patients in the nation per year.
At the University of Miami, Dr. Silver teamed up with infectious disease specialist Dr. Gordon Dickinson at the Bruce W. Carter Veterans Affairs Medical Center to establish a cohort of 10 elite controllers of HIV-1 infection. The goal of this effort was to determine to what extent initial infection by HIV-1 strains with unusual, difficult to revert mutations might explain long-term virologic control and lack of AIDS progression in the absence of antiretroviral drug therapy.
“The administration of broadly neutralizing antibodies represents the next wave of treatment for HIV-infected individuals,” said Dr. Silver. “We discovered that some strains of HIV-1 evolve long variable domains in their Envelope protein and that this lengthening confers the Envelope with sugars called O-glycans. These O-glycans are highly effective at preventing certain broadly neutralizing antibodies from binding and inhibiting HIV-1 infection of new cells. In other words, the virus continues to find a way to evade our best defense mechanisms and this will present a hurdle that needs to be overcome as we move forward with antibodies as our next therapeutic strategy.”
“Now, some 36 years after the discovery of HIV-1 as the cause of AIDS, there is an enormous amount of detailed knowledge regarding the structural elements and replication strategies of the virus,” said Dr. Desrosiers. “Discovery of new fundamental features of HIV-1's structural elements, replicative strategies, and evasion strategies is now quite uncommon. Zach is now on a shortlist with his discovery.”
Dr. Desrosiers says the work is so significant that Dr. Silver will be first author on a high impact publication. He also has two additional papers underway.
Dr. Silver’s work has been highly rated and acknowledged by the National Institutes of Health. He received a four-year F30 fellowship from them for his study of viral genetic elements that may contribute to HIV elite control. He presented at the annual M.D./Ph.D. symposium in April 2019, where he was awarded “Best Talk,” and in 2017 was awarded a scholarship by the Clinical and Translational Science Institute at UM to attend a translational science course at the University of Utrecht in The Netherlands.
Stephan Züchner, M.D., Ph.D., chair of the Dr. John T. Macdonald Foundation Department of Human Genetics, says the recipients’ work is helping to understand important diseases and may help develop therapies in the future.
“This award is wonderful because it recognizes the important work they are doing to advance science and, ultimately, medicine,” said Dr. Züchner, who is also a professor of neurology and co-director of the John P. Hussman Institute for Human Genomics.
A prominent force in the field of biochemical genetics, Dr. Elsas was also a clinician who knew the promise of research. He came to UM in 2002 thanks to another generous multimillion-dollar gift from the Dr. John T. Macdonald Foundation, which allowed the university to establish a new program in medical genetics.
R. Rodney Howell, M.D., professor and chair emeritus of the Department of Pediatrics, a fellow geneticist, pediatrician, and longtime friend, recruited Dr. Elsas.
“It is essential to our university that the Dr. John T. Macdonald Foundation has endowed this award to honor Dr. Skip Elsas,” said Dr. Howell, who chaired the award committee and is a board member of the Dr. John T. Macdonald Foundation. “It provides important support to the careers of young professionals who will shape the growing field of medical genetics for years to come.”