BME Lecture Series: Luke Lairson, Scripps Research Institute
Assistant Professor of Chemistry
Abstract: The Lairson research laboratory uses a chemical biology approach to study cell fate- and cell state-determining processes that play a causative role in the progression of human disease. We have ongoing research programs in areas ranging from the selective induction of endogenous stem cell differentiation to the modulation of immunological response within tumor microenvironments. The majority of our research projects involve the use of prospectively isolated primary patient-derived human or engineered rodent cell types, which are used to mimic disease-related process in miniaturized formats. Using the tools of structural diversity and high-throughput phenotype-based discovery, typically involving high-content imaging or high-throughput flow cytometry, small molecules are identified that selectively induce a desired impact on cell fate (e.g., induced differentiation toward a defined lineage) or cell state (e.g., immune checkpoint protein display in response to tumor microenvironment). Validated hit compounds, demonstrated to function via a novel mechanism, are subjected to parallel structure-activity relationship studies and medicinal chemistry-based optimization, as well as target identification and mechanism of action studies. Optimized molecules, possessing suitable pharmacokinetic and target engagement properties, are evaluated in relevant rodent models of disease to assess the relevance of identified mechanisms to disease state. Potential molecular targets are identified using diverse mass spectrometry-based proteomics approaches involving synthesized photo-activatable affinity probe reagents. Downstream mechanism(s) of action are elucidated using standard cell and molecular biology-based techniques.
Bio: Lairson obtained his bachelor's degree in biochemistry from the University of Guelph and his doctorate in chemistry from the University of British Columbia. He performed postdoctoral research in the fields of chemical biology and regenerative medicin, as a CIHR fellow at the Scripps Research Institute. Lairson worked as a research investigator at the Genomics Institute of the Novartis Research Foundation (GNF) in the fields of regenerative medicine and preclinical drug development. He went on to become a founding member of the California Institute for Biomedical Research (Calibr), where he served as director of high-throughput discovery and principal investigator. He is currently an assistant professor in the Department of Chemistry at the Scripps Research Institute.