Penn Medicine Awarded $6 Million to Advance Understanding of Human Genome Function in Health and Disease

PHILADELPHIA— The National Institutes of Health (NIH) has selected Penn Medicine as one of 25 award recipients across 30 sites in the United States to serve as Impact of Genomic Variation on Function (IGVF) investigators, with the goal of better understanding how genetic differences impact how human genes function, and how these variations influence human health and disease. Funded by the NIH’s National Human Genome Research Institute (NHGRI), Penn Medicine will be awarded more than $1.2 million per year, with a contract that is expected to be supported for five years, totaling more than $6 million in funding for this research.

While genome sequences among people are more than 99.9 percent identical, it’s the 0.1 percent of differences, alternate orders of the As, Cs, Gs and Ts that make up DNA, combined with environment and lifestyle, that shape a person’s overall physical features and disease risk. Researchers have identified millions of human genomic variants that differ across the world, including thousands associated with disease. With results from this new research and advanced computer modeling, Penn and other IGVF consortium investigators aim to identify which variants in the genome are relevant for health and disease, with major implications for physicians and their patients.  

“A fundamental question in biology is to understand how genetic variation affects genome function to influence human health and diseases,” said Hao Wu, PhD, an assistant professor of Genetics in the Perelman School of Medicine at the University of Pennsylvania, who will serve as the Penn site’s principal investigator. “With the IGVF award, we can leverage the brain power of Penn’s experts in human genetics, single cell sequencing and functional genomics to decode how genetic variants may contribute to how genes are regulated, how cells function, and ultimately, human diseases. This is a terrific opportunity for collaboration with researchers across departments and institutions.”

Penn Medicine site researchers will focus on the dynamic processes of generating human heart and brain cells, investigating the impact of genomic variants from ethnically diverse populations on the regulatory networks that control gene expression. This effort will generate a detailed functional map of genetic and epigenetic landscapes in early lineages of human heart and brain cells, allowing researchers to dive further into how genes and non-coding regulatory sequences play a role in human congenital heart or brain diseases.

The IGVF consortium plans to develop a catalog of the results and approaches used in their studies and share this information through a web portal to assist the research community with future projects. Since there are thousands of genomic variants associated with disease, and it is not possible to manipulate each variant individually and in each biological setting, consortium researchers will also develop computational modeling approaches to predict the impact of variants on genome function.

The Penn Medicine site will be co-led by Hongjun Song, PhD, a professor of Neuroscience at the Perelman School of Medicine at the University of Pennsylvania, and Sreeram Kannan, PhD, an assistant professor of Electrical & Computer Engineering at University of Washington, Seattle. Other researchers from Penn include Sarah Tishkoff, PhD, the David and Lyn Silfen University Professor of Genetics and Biology, Guo-li Ming, MD, PhD, the Perelman Professor of Neuroscience, Kiran Musunuru, MD, PhD, MPH, a professor of Medicine, Junwei Shi, PhD, an assistant professor of Cancer Biology, Ziyue Gao, PhD, an assistant Professor of Genetics, and Wenli Yang, PhD, a research assistant professor of Medicine.