Rewrite, Reprogram, and Regenerate: from CRISPR to Stem Cell Models of Human Health and Disease

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Monday,  January 31, 2022
3:30 – 5:00 p.m.
On Zoom

Abstract

The research of the Stem Cell and Regeneration Laboratory aims to understand the regenerative mechanisms that maintain the proper form and function of the human body. Achieving this would require genetically tractable human cellular models that faithfully recapitulate human physiology. Genome editing and pluripotent stem cells (PSCs) have synergistically facilitated the development of such models to study the mechanisms of cellular differentiation and disease, screen for drugs, and develop advanced gene and cell therapy. However, many fundamental aspects of these two essential tools remain unexplored, which hampers the progress of the regenerative medicine field. I identified two main research questions to focus on as an assistant professor: 1) to push the understanding of genetic heterogeneity of stem cells (e.g., after CRISPR genome editing) to the single-molecule and single-cell level; 2) to use genetic- and bio-engineering approaches to build cellular models that better recapitulate human (patho)physiology. I leveraged a multidisciplinary platform that integrates cellular reprogramming, PSCs, genome engineering, functional genomics, and bioengineering to address these challenging questions, while keeping a commitment to fulfilling the translational promise of stem cell research. 

I will summarize the progress we made in the last five years in the following areas: 1) long-read individual-molecule sequencing for analysis of large structural variants induced by CRISPR-Cas9 in human PSCs and analysis of genetic variants in the complete mitochondrial genome in single germ cells; 2) building isogenic iPSC models of Wiskott-Aldrich syndrome to reveal disease mechanisms; 3) modeling human early embryogenesis using stem cell-based blastocyst-like 3D structures; 4) In situ monitoring and controlling cellular environment in human stem cell culture. Finally, I’ll discuss our translational work on COVID-19 and Saudi genetic disease diagnosis and my future research plans.  

About the speaker

Mo Li is an Assistant Professor of Bioscience at King Abdullah University of Science and Technology (KAUST). He received his B.Sc. from Peking University (China) and his Ph.D. in cellular biology from the University of Georgia (USA). He trained as a postdoc in the lab of Juan Carlos Izpisua Belmonte at the Salk Institute (USA). His lab focuses on using pluripotent stem cells, cellular reprogramming, and genome editing technologies to understand the mechanisms of disease and regeneration. His lab has developed novel nanopore sequencing methods for resolving genetic heterogeneity in stem cells and novel stem cell models for studying human disease and biology. He has published over 60 papers in international journals, including Nature, Science, New England Journal of Medicine, and Genome Biology, in the areas of stem cells and genome editing.

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