Michael C. Bassik, PhD, Assistant Professor, Department of Genetics, Stanford University School of Medicine
Research Description: The Bassik lab uses high-complexity shRNA libraries and systematic genetic interaction maps in mammalian cells to understand the biology of endocytic pathogens as well as stress signaling to the cell death machinery. At the same time, we develop novel tools for conducting genetic screens and generating interaction maps. We have been working together with ~25 collaborating labs at Stanford and beyond to use our technologies to functionally annotate the genome in health and disease states, including diabetes mellitus. We created genome-wide CRISPR/Cas9 sgRNA libraries, and have used these in parallel with our shRNA libraries to conduct ~150 genome-wide screens successfully. To perform genetic interaction studies using the CRISPR/Cas9 system, we have developed a double sgRNA platform that allows the simultaneous measurement of 105-106 sgRNA pairs by deep sequencing. A major focus of the work has been to use pairwise double-shRNA vectors to develop a genetic interaction map to study the control of ER-trafficking (using the toxin ricin). The study of this system and lessons learned may be used to better understand questions relevant to β-cell biology, e.g., insulin packaging. Dr. Bassik is collaborating with Drs. J. Annes and Seung Kim to better understand the genetic factors that control insulin packaging, storage and secretion. These cross-disciplinary interactions bring new scientists, techniques and insights to the diabetes field. The wide range of applications to translational science for which the Bassik lab has been funded highlight the broad applicability of this work and potential to contribute to the diabetes research environment at Stanford.
Selected relevant publications (Stanford DRC Members in BOLD):
1. Gu S, Zhang Y, Jin L, Huang Y, Zhang F, Bassik MC, Kampmann M, Kay MA. Weak base pairing in both seed and 3' regions reduces RNAi off-targets and enhances si/shRNA designs. Nucleic Acids Res 42:12169-76, 2014.
2. Deans RM, Morgens DW, Ökesli A, Pillay S, Horlbeck MA, Kampmann M, Gilbert LA, Li A, Mateo R, Smith M, Glenn JS, Carette JE, Khosla C, Bassik MC. Parallel shRNA and CRISPR-Cas9 screens enable antiviral drug target identification. Nat Chem Biol. 12:361-6, 2016.