The National Institutes of Health (NIH) has awarded grants to researchers 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 recipients are among 106 national awardees:
New Innovator Awards
Harnessing Sensory Food Circuits to Influence Feeding Behavior
Alhadeff, an adjunct assistant professor of neuroscience in the Perelman School of Medicine and principal investigator at the Monell Chemical Senses Center, 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 the understanding of how our brain and environment interact to promote overeating and obesity.
Peter S. Choi
Exploring Hidden Determinants of Splicing with Genome-Targeted Proximity Labeling
Choi, an assistant professor of pathology and laboratory medicine in the Perelman School of 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.
The Epigenetic Encoding of Learning and Memory
Korb, an assistant professor of genetics in the Perelman School of Medicine, 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 people to learn, adapt, and become who they are today.
Quantifying the Dynamics of Gene Regulation and Nuclear Organization During Embryogenesis
Mir, an assistant professor of cell and developmental biology in the Perelman School of Medicine and the Children’s Hospital of Philadelphia, 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 gained from the proposed experiments has 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.
Illuminating Transcriptional Condensates Using an Integrated Approach
Wan, an assistant professor of cancer biology in the Perelman School of Medicine, 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 to target gene dysregulation in cancer and other diseases.
Transformative Research Award
Ben Black and Michael Lampson
Mendelian Inheritance of Artificial Chromosomes
Black, the Eldridge Reeves Johnson Foundation Professor of Biochemistry and Biophysics in the Perelman School of Medicine, and Michael Lampson, a professor of biology in the School of Arts & Sciences, are co-principal investigators on a project 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.
From 3D Genomes to Neural Connectomes: Higher-Order Chromatin Mechanisms Encoding Long-Term Memory
Phillips-Cremins is an associate professor and Dean’s Faculty Fellow in bioengineering and genetics, with appointments in the School of Engineering and Applied Science and the Perelman School of Medicine. She 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 in the onset and progression of neurodevelopmental and neurodegenerative disorders.