Randall T. Peterson, PhD is a chemical biologist whose research utilizes high-throughput screening technologies to discover new drug candidates for cardiovascular and nervous system disorders. Unlike conventional drug discovery programs that utilize simplified, in vitro assays, the Peterson lab screens using living zebrafish, ensuring that the drug candidates discovered are active in vivo. Several of the compounds discovered by the Peterson laboratory have become widely used research tools or preclinical drug candidates.
Dr. Peterson received his PhD from Harvard University where he studied as a Howard Hughes Medical Institute predoctoral fellow in the laboratory of Stuart Schreiber. He completed a postdoctoral fellowship with Mark Fishman at Massachusetts General Hospital. Dr. Peterson spent 14 years as a faculty member at Harvard University where he was the Charles Addison and Elizabeth Ann Sanders Chair in Basic Science at Harvard Medical School, Scientific Director of the MGH Cardiovascular Research Center, and Senior Associate Member of the Broad Institute. In 2017 he moved to the University of Utah as L.S. Skaggs Presidential Endowed Professor and Dean of the College of Pharmacy.
Small molecules are powerful tools for studying developmental biology because they provide timing and dosage control over developmental pathways that is difficult to achieve with genetic mutations. Unfortunately, only a handful of developmental pathways can currently be targeted with small molecules. We are discovering novel chemical modifiers of developmental pathways by exposing zebrafish embryos to libraries of structurally diverse small molecules and identifying those that induce specific developmental defects. Using screens of this type, we have discovered dozens of compounds that cause specific defects in hematopoesis, cardiac physiology, embryonic patterning, pigmentation, and morphogenesis of the heart, brain, ear, and eye and germ cell lineage.
One focus of our group is modeling human diseases in zebrafish. We then use the models to screen large chemical libraries for small molecule modulators of the disease-related phenotypes. The compounds we discover help us elucidate disease mechanisms and serve as starting points for developing new drug candidates.
Disease physiology is often complex and involves interactions between multiple organs and tissue types. Consequently, many diseases cannot be studied effectively using in vitro assays. The zebrafish is an excellent vertebrate model system to study many complex, non-cell autonomous diseases because the diseases can be studied in a native, whole-organism setting. In addition, compounds discovered in zebrafish screens have the advantage of having been selected for their ability to be active, efficacious, and well tolerated in animals.
Neuroscience & Behavior
Behaviors are accessible readouts of the molecular pathways that control neuronal signaling. Our group develops tools and techniques for comprehensive and high-throughput behavioral phenotyping in the zebrafish. These tools have some potential to improve our understanding of the neuronal signlaing and may accelerate the pace of neuroactive drug discovery.
Zebrafish Reverse Genetics
Zebrafish have proven to be a powerful genetic tool over the years, primarily through forward genetic screens where fish are mutagenized (typically with chemical agent) and screened for obvious defects. We are now on the verge of the next exciting step in zebrafish genetics: reverse genetics! Using targeted DNA disruption, we are now making designer mutations in specific genes of interest. Here are some of the resent papers describing three different processes.