NIH awards more than $8 million to support seven high-risk, high-reward projects at Penn Medicine

The National Institutes of Health has awarded grants to researchers in the Perelman School of Medicine at the University of Pennsylvania to support "highly innovative and broadly impactful" biomedical science through the NIH Common Fund's High-Risk, High-Reward Research program. The seven awards total approximately $8.2 million over five years,

The High-Risk, High-Reward Research program catalyzes scientific discovery by supporting research proposals that, due to their inherent risk, may struggle in the traditional peer-review process, despite their transformative potential. Program applicants are encouraged to pursue trailblazing ideas in any area of research relevant to the NIH's mission to advance knowledge and enhance health.

The 2021 Penn Medicine recipients are among 106 national awardees:

New innovator awards

Amber Alhadeff, PhD

Harnessing Sensory Food Circuits to Influence Feeding Behavior

Alhadeff, an adjunct assistant professor of Neuroscience, is taking a unique approach to understanding obesity by evaluating the power of taste, smell, and nutrient neural circuits in modifying eating behavior. Her team will also uncover how sensory and nutritive information is integrated in the brains of mice to predict future weight gain. Successful completion of this project will transform our understanding of how our brain and environment interact to promote overeating and obesity.

Peter S. Choi, PhD

Exploring Hidden Determinants of Splicing with Genome-Targeted Proximity Labeling

Choi, an assistant professor of Pathology and Laboratory Medicine, will examine the connection between epigenetics and RNA splicing to uncover their relationship in both healthy and unhealthy contexts, as well as to identify new opportunities for therapeutic intervention in diseases such as cancer.

Erica Korb, PhD

The Epigenetic Encoding of Learning and Memory

Korb, an assistant professor of Genetics, will seek to uncover the transcriptional signature encoding a memory within a neuron and how this is influenced by epigenetic mechanisms. Through this work, Korb's lab hopes to understand how the physical world influences gene regulation in the brain to allow us to learn, adapt, and become the people we are today.

Mustafa Mir, PhD

Quantifying the Dynamics of Gene Regulation and Nuclear Organization During Embryogenesis

Mir, an assistant professor of Cell and Developmental Biology, will integrate cutting-edge techniques to directly visualize and quantify how the regulation of gene expression is orchestrated during embryonic development. The critical new information that will be gained from the proposed experiments have the potential to lead to novel therapeutic approaches to prevent or repair defects that arise from aberrant gene expression during development, in aging, and in cancer.

Liling Wang, PhD

Illuminating Transcriptional Condensates Using an Integrated Approach

Wang, an assistant professor of Cancer Biology, is investigating the functions and mechanisms of a newly-recognized form of transcriptional assembly, in order to better understand gene regulation. Successful completion of this project would establish a new model of gene control and have the potential to transform how we target gene dysregulation in cancer and other diseases.

Transformative research awards

Ben Black, PhD

Mendelian Inheritance of Artificial Chromosomes

Black, an associate professor of Biochemistry and Biophysics, along with co-principal investigator Michael Lampson, PhD, a professor of Biology, are aiming to construct the first synthetic mammalian artificial chromosomes that follow Mendel's laws, from minimal components. Success will transform fundamental understanding of what comprises a mammalian chromosome and have wide-ranging applications in synthetic biology and biotechnology, such as creation of animal models for drug development and as sources of personalized organs for transplantation.

Pioneer awards

Jennifer Phillips-Cremins, PhD

From 3D Genomes to Neural Connectomes: Higher-Order Chromatin Mechanisms Encoding Long-Term Memory

Phillips-Cremins, PhD, an associate professor of Bioengineering and Genetics, is seeking to unravel the functional link between long-range 3D genome folding patterns and synaptic plasticity during the encoding of long-term memory in the mammalian brain. Because many key neurological disorders are thought to be diseases of the synapse, successful completion of this work will provide a foundation for future studies unraveling the role for misfolded genome topology on the onset and progression of neurodevelopmental and neurodegenerative disorders.