High-Risk, High-Reward Grants Go to Two CHOP Researchers

Two scientists at Children’s Hospital of Philadelphia (CHOP) have just received highly competitive five-year awards from the National Institutes of Health (NIH) to advance their promising research on the leading edge of biomedicine: one project in prenatal gene editing to treat congenital disorders, the other for the development of novel functional genomics tools for studying protein function at large scale in human health and disease. Both researchers use CRISPR — the powerful gene-editing tool that harnesses an enzyme to cut and paste genetic instructions at a precise location in a DNA sequence.

The NIH Director’s New Innovator Awards support unusually innovative research by early-career investigators, under the broader umbrella of the High-Risk, High-Rewards Program of the NIH Common Fund. The NIH describes High-Risk, High-Rewards Programs as “unconventional approaches to major challenges in biomedical and behavioral research.” The newly announced New Innovator Awards recognize 60 researchers throughout the U.S. Each of the two grants to CHOP researchers include direct costs of $1.5 million over a five-year period.

William H. Peranteau, MD William H. Peranteau, MD, an investigator at CHOP’s Center for Fetal Research, and a pediatric and fetal surgeon in CHOP’s Center for Fetal Diagnosis and Treatment, received grant DP2 HL152427, entitled “In Utero CRISPR-mediated Gene Editing to Cure Congenital Monogenic Disorders.” His research focuses on using CRISPR gene editing to cure or reduce the severity of genetic disorders before birth.

Peranteau has co-led and published two proof-of-concept studies in animal models of congenital diseases. A 2018 study of a liver disease was the first time that prenatal CRISPR-mediated gene editing prevented a lethal metabolic disease in animals. A second study used prenatal CRISPR gene editing in a mouse model of a congenital lung disease to mitigate its perinatal lethality. The New Innovator Award will allow his team to explore its use in other congenital disorders.

Ophir Shalem, PhD Ophir Shalem, PhD, of CHOP’s Raymond G. Perelman Center for Cellular and Molecular Therapeutics and the Department of Genetics in the Perelman School of Medicine at the University of Pennsylvania, received grant DP2 GM137416, entitled “Direct and Rapid Control of Proteins at Scale.” His research focuses on developing and applying tools for functional genomics: approaches that aim to study protein function by direct, large-scale perturbations.

As a postdoctoral researcher, Shalem was one of the pioneers in using the CRISPR system to develop genome-wide loss-of-function screens in mammalian cells. With funding from the New Innovator Award, his team will develop new functional genomics tools that rely on precise gene tagging. Using a method that his lab recently developed, the team will fuse thousands of proteins produced within the organism with a variety of small peptide tags. This will permit many important applications not feasible under previous approaches, such as parallel measurements of gene expression dynamics for thousands of proteins, direct and rapid control of protein function, and a high-resolution study of protein unfolding that is associated with many human diseases.

Read more in the NIH press release announcing the 2019 High-Risk, High-Reward grants. Also see @NIH_CommonFund and #NIHHighRisk on Twitter.