Miller School’s Dr. Leor Weinberger Earns NIH’s Most Prestigious Award
After decades developing a therapy designed to evolve alongside HIV, Leor Weinberger, Ph.D., is applying the same concept to some of the deadliest cancers, with support from the NIH Director’s Pioneer Award.
Key Takeaways
- Viruses and cancer cells can mutate in ways that allow them to escape treatment.
- Leor Weinberger, Ph.D., is investigating therapies designed to evolve alongside disease.
- The cancer research builds on an experimental therapeutic strategy first developed for HIV.
- The early-stage work will focus on pancreatic cancer, glioblastoma and acute myeloid leukemia.
After pancreatic cancer claimed the life of a close family friend who had tried every therapy available, virologist Leor Weinberger, Ph.D., set out to build a new class of anti-cancer medicines based on an antiviral therapy he had developed.
Today, Dr. Weinberger, a faculty member of Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, was awarded the NIH’s most prestigious award, the NIH Director’s Pioneer Award, for his “high-risk, high-reward research” to develop a novel cancer therapy.
As a young graduate student studying the biophysics of HIV, Leor Weinberger, Ph.D., was consumed by a simple yet profound insight. A fundamental mismatch exists between viruses and the therapies developed to treat them.
“Like cancers, viruses mutate,” said Dr. Weinberger, the founding chair of the Department of Cell and Systems Biology at the Miller School. “But for over 100 years, we’ve been using static, chemistry-based technologies to treat these dynamic, evolving biological systems.”
Failure, Failure, Failure…Success
Dr. Weinberger has dedicated his career to solving this problem. The most rational solution, he thought, was to build a therapy that can also mutate, so the drug could not be circumvented by mutation. Instead, the therapy would evolve together with the virus.
For more than 20 years, few believed it could work.
“In very polite and sophisticated ways, almost everyone told me the idea was ridiculous,” Dr. Weinberger said. “It does not exist. You won’t find it. Stop working on it.”
Dr. Weinberger forged ahead, sometimes spending years working in a direction that amounted to nothing. The first time he won an NIH Director’s Pioneer Award in 2013, he spent years engineering 150,000 therapeutic candidates, all of which failed.
Until one didn’t.
One day, a postdoc in Dr. Weinberger’s lab brought him a picture of the amputated genetic material they had been pursuing for 20 years. It had evolved by itself in a flask in the back of the lab. That foothold led to pre-clinical trials that worked exactly as Dr. Weinberger had imagined 20 years earlier, protecting cells from HIV. His work, chronicled in the New York Times, earned numerous awards including the NIH Director’s Transformative Research Award, New Innovator Award and Avant-Garde Award, as well as recognitions from the Blavatnik Family Foundation, Sloan Foundation and the Pew Charitable Trusts.
“It’s not perfectly sane to follow something for decades when it keeps failing, but when success is a medicine that could help millions of people, you keep going,” said Dr. Weinberger.
The HIV therapy is now in the final stages of FDA review for clinical trials.
How Did HIV Research Lead to a New Therapeutic Strategy?
Dr. Weinberger has now turned his attention to the pressing problem of cancer.
“Like viruses, cancer cells evolve, resulting in resistant tumors that escape therapy and are not susceptible to treatment,” he said. “It’s a fundamental problem across broad domains of biology.”
In biology, there’s an evolutionary concept called the Red Queen Hypothesis, taken from the character’s quote in Lewis Carroll’s “Through the Looking-Glass.”
“It takes all the running you can do, to keep in the same place.”
This co-evolutionary arms race means a biological system like a virus continually counter-evolves while the host tries to evolve resistance and mutate away or “escape.” Both end up running in place.
“We are developing a therapy that can establish a scenario analogous to Lewis Carroll’s Red Queen, a therapy that can run after the tumor as it tries to run away,” said Dr. Weinberger.
Building on a New Treatment Modality with Broad Applications
Now that Dr. Weinberger has a precedent for a therapeutic that can keep up with the rapid evolution of HIV, it seems likely that pivoting to cancer will be much faster.
“In 2020, we were able to produce a COVID therapeutic candidate based on this concept in about 18 months. We believe the same concepts can be used to rapidly build a new class of therapeutics across all of these domains, including deadly cancers like pancreatic cancer,” he said.
The cancer work is early, but his lab has already shown proof of concept for a therapy that can evolve with a tumor. The Pioneer Award provides five years of funding with few strings attached.
His research will focus on three different types of cancer with poor survival rates, due in part to their broad genetic diversity: pancreatic cancer, glioblastoma and acute myeloid leukemia.
Finding a Home for Patient-Focused Research in South Florida
Dr. Weinberger moved to the Miller School in 2025 to pursue this new cancer therapy through its Phase 1 clinical trial unit for experimental therapeutics.
“I can think of no better place than Sylvester to take this concept to clinical trial. It’s a place designed to propel therapeutic concepts to the clinic. In some cases, clinical colleagues have indicated that if the medical need is dire enough, they will move directly to testing in patients not to delay a potentially life-saving medicine,” he said.
Dr. Weinberger calls the novel therapy they’re building a neoplasm emergent oncolytic virus, or a neovirus, based on existing tumor-busting viruses that only infect tumor cells and with a nod to the movie, “The Matrix.”
The possibility of successfully building a novel therapy to treat cancer is Dr. Weinberger’s all-consuming obsession now, building on his HIV viral treatment that’s entering clinical trials.
“If the reward is significant enough—for example, overcoming pancreatic cancer—it’s worth the possibility of failure,” he said.
With the Miller School’s integrated bench-to-bedside model and the region’s rapidly expanding aging population, this award places Dr. Weinberger and his team in the ideal environment to build a new class of anti-cancer medicines for those who need it most.
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Tags: Acute Myeloid Leukemia, cancer research, Department of Cell and Systems Biology, Dr. Leor Weinberger, glioblastomas, Newsroom, pancreatic cancer, Sylvester Comprehensive Cancer Center