MCDB Seminar Series: Elucidating cellular and molecular mechanisms of neurodegenerative diseases with CRISPR-based functional genomics

Speaker

Martin Kampmann

Date and Location

Thursday October 11, 2018 12:30pm
Rathmann Auditorium (LSB 1001)

Abstract

Hosted by: Diego Acosta-Alvear

Martin Kampmann Assistant Professor of Biochemistry and Biophysics, University of California, San Francisco

Elucidating cellular and molecular mechanisms of neurodegenerative diseases with CRISPR-based functional genomics

Abstract: Human genes associated with disease are being discovered at an accelerating pace. A major challenge is the identification of the mechanisms through which these genes act, and of potential therapeutic strategies. To elucidate such mechanisms in human cells, we are leveraging a CRISPR-based platform for genetic screening that we recently co-developed. Our approach relies on CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa), in which a catalytically dead version of the bacterial Cas9 protein recruits transcriptional repressors or activators, respectively, to endogenous genes to control their expression, as directed by a small guide RNA (sgRNA). Complex libraries of sgRNAs enable us to conduct genome-wide loss-of-function and gain-of-function screens in mammalian cells. We have adapted this strategy for use in human iPSC-derived neurons and other cell types, in order to elucidate disease mechanisms and therapeutic strategies for neurodegenerative diseases. Our pilot screens systematically reveal genes and cellular pathways controlling neuronal survival and the aggregation of the protein tau, which is associated with Alzheimer's Disease and other tauopathies.
Biography: Dr. Kampmann received his BA in Biochemistry from Cambridge University (UK) and his PhD in Biophysics and Cell Biology from The Rockefeller University. As a postdoctoral fellow at UCSF, he spearheaded the development of a next-generation genetic screening platform for mammalian cells, which incorporates systematic genetic interaction maps and CRISPR-based gain- and loss-of-function screens.
The goal of Dr. Kampmann’s research is to elucidate cellular mechanisms of human diseases and to develop new therapeutic strategies. For this purpose, his lab has pioneered CRISPR-based genetic screening technology in cell types derived from induced pluripotent stem cells (iPSCs). A major focus is the investigation of neurodegenerative diseases in human iPSC-derived neurons, astrocytes, and microglia. The technology platform co-developed by Dr. Kampmann positions him uniquely to uncover cellular mechanisms controlling these diseases. Dr. Kampmann has also successfully applied his technology to reveal the mechanism of action of new drugs, and to identify biomarkers that predict the response of patients to a given therapy – a central goal of Precision Medicine.