NIH Awards $8.2M to Seven Penn Medicine Researchers for High-Risk, High-Reward Projects

Seven researchers at the University of Pennsylvania's Perelman School of Medicine have won a combined $8.2 million in grants from the National Institutes of Health, part of a national initiative designed to fund the kind of ambitious, unconventional science that traditional grant review often rejects. The awards, distributed over five years, come through the NIH Common Fund's High-Risk, High-Reward Research program, which exists precisely to support work that is too speculative or too far outside established frameworks to survive standard peer review, yet carries genuine potential to reshape how we understand disease and biology.

The program operates on a simple premise: transformative breakthroughs often require risk. Researchers are invited to pursue ideas that might fail but could, if successful, fundamentally change a field. The seven Penn Medicine recipients are among 106 awardees nationally, each pursuing work that sits at the frontier of their discipline.

Amber Alhadeff, an adjunct assistant professor of neuroscience, is investigating how taste, smell, and the brain's nutrient-sensing circuits shape eating behavior and weight gain. Her team will work with mice to understand how sensory and nutritive signals integrate in the brain to predict future obesity—research that could reframe how we think about overeating not as a matter of willpower but as a problem of neural circuitry responding to environmental cues. Peter Choi, an assistant professor of pathology and laboratory medicine, is examining the relationship between epigenetics and RNA splicing, the cellular machinery that determines which genes get expressed. His work could reveal new vulnerabilities in cancer cells and open therapeutic pathways currently invisible. Erica Korb, an assistant professor of genetics, is pursuing the physical basis of memory itself—how the brain encodes learning through changes in gene regulation, and how the external world literally reshapes the genetic machinery inside neurons.

Mustafa Mir, an assistant professor of cell and developmental biology, is developing techniques to directly visualize how genes are regulated during embryonic development, work that could eventually lead to treatments for birth defects and age-related diseases. Liling Wang, an assistant professor of cancer biology, is investigating transcriptional condensates, a newly recognized form of cellular assembly that controls gene expression, with the goal of understanding how cancer cells hijack these mechanisms and how to stop them.

Two researchers received the program's highest tier of support. Ben Black, an associate professor of biochemistry and biophysics, working with Michael Lampson, a professor of biology, is attempting to build the first synthetic mammalian chromosomes that obey Mendel's laws of inheritance—a feat that could unlock new approaches to creating animal models for drug testing and eventually to growing replacement organs. Jennifer Phillips-Cremins, an associate professor of bioengineering and genetics, is seeking to connect the three-dimensional folding patterns of the genome to the synaptic changes that underlie long-term memory, work that could illuminate why so many neurological disorders involve problems with synaptic function and how misfolded genome architecture might contribute to neurodevelopmental and neurodegenerative disease.

What unites these projects is their refusal to work within existing boundaries. They are not incremental improvements on established methods but attempts to see biological systems in fundamentally new ways. The NIH's willingness to fund them reflects a recognition that the most important discoveries often come from researchers willing to bet their reputation on an idea that might not work—and that institutions need to create space for that kind of intellectual risk.