Bridget Wagner, PhD, Broad Institute, Webinar

Moderator: Bridget Wagner, Ph.D, Director of Pancreatic Cell Biology and Metabolic Disease, Harvard University

Webinar title: Characterizing cellular injury in high-content cellular morphology assays

Abstract: Robust, generalizable approaches to identify compounds efficiently with undesirable mechanisms of action in complex cellular assays remain elusive. Such a process would be useful for hit triage during high-throughput screening and, ultimately, predictive toxicology during drug development. Here we generate cell painting and cellular health profiles for 218 prototypical cytotoxic and nuisance compounds in U-2 OS cells in a concentration-response format. A diversity of compounds that cause cellular damage produces bioactive cell painting morphologies, including cytoskeletal poisons, genotoxins, nonspecific electrophiles, and redox-active compounds. Further, we show that lower quality lysine acetyltransferase inhibitors and nonspecific electrophiles can be distinguished from more selective counterparts. We propose that the purposeful inclusion of cytotoxic and nuisance reference compounds such as those profiled in this resource will help with assay optimization and compound prioritization in complex cellular assays like cell painting.

Presenter:

Jayme L. Dahlin is a physician scientist currently working in the pharmaceutical industry. After earning his M.D. and Ph.D. from the Mayo Clinic, he completed a clinical residency in clinical pathology at Brigham and Women’s Hospital/Harvard Medical School. Dr. Dahlin then completed a postdoctoral fellowship in chemical biology at the Broad Institute, where he studied the effects of nuisance compounds in complex cellular assays in the laboratories of Drs. Stuart L. Schreiber and Bridget K. Wagner. After completing his training, he performed chemical biology research at the National Center for Advancing Translational Sciences (NCATS), part of the United States National Institutes of Health (NIH), before transitioning to industry. Dr. Dahlin is board-certified in clinical pathology from the American Board of Pathology, and currently serves as on the scientific editorial boards of the NIH Assay Guidance Manual and the Chemical Probes Portal. He has authored more than 60 peer-reviewed publications in the fields of early drug discovery, nuisance compounds, and assay development.