Lay Teng Ang

Lay Teng Ang, PhD, Siebel Investigator and Instructor, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine

Research description: Dr. Ang's ultimate research goal is to convert stem cells into specific cell-types at high precision and efficiency for a variety of practical applications (e.g., disease modeling, cell therapy, and drug toxicity testing). Her work over the past 10 years has centered on human pluripotent stem cells (human PSCs, which include embryonic and induced pluripotent stem cells), which have the remarkable ability to generate any of the hundreds of diverse cell-types in the body. However, it has been notoriously difficult to differentiate PSCs into a pure population of a given cell-type. Current differentiation strategies typically generate heterogeneous cell populations unsuitable for basic research or clinical applications. To address this challenge, Dr. Ang mapped the cascade of branching lineage choices through which human PSCs differentiate into a variety of endodermal and mesodermal cell-types. She then developed effective methods to differentiate PSCs into specific lineages by providing the extracellular signal(s) that specify a given lineage while inhibiting the signals that induce the alternate fate(s). Using this strategy, her team produced highly-pure populations of human heart and bone progenitors (Loh & Chen et al., 2016; Cell) and hepatocytes/liver precursors (Loh & Ang et al., 2014; Cell Stem Cell; Ang et al., 2018; Cell Reports) from PSCs. Of particular relevance to the SDRC's research goals, Dr. Ang has specifically focused on generating highly-pure populations of human hepatocytes from PSCs to establish in vitro cellular models of fatty liver disease. Her current objectives are to model non-alcoholic fatty liver disease (NAFLD) using genetically-diverse PSC-derived hepatocytes and to comprehensively detail the molecular signature of human ESC-derived healthy vs. “fatty” hepatocytes. Ultimately, achieving these goals holds promise for identifying new genetic risk factors for NAFLD and Type 2 Diabetes for identifying new targets for therapeutic interventions. 

Selected relevant publications (SDRC Members in BOLD):

  1. Fowler JL, Ang LT, Loh KM. A critical look: Challenges in differentiating human pluripotent stem cells into desired cell types and organoids. Wiley Interdiscip Rev Dev Biol. 2020 May;9(3):e368. doi:10.1002/wdev.368. PMID: 31746148; PMCID: PMC7397816.

  2. Loh KM, Palaria A, Ang LT. Efficient Differentiation of Human Pluripotent Stem Cells into Liver Cells. J Vis Exp. 2019 Jun 11;(148). doi:10.3791/58975. PMID: 31259908.

  3. Ang LT, Tan AKY, Autio MI, Goh SH, Choo SH, Lee KL, Tan J, Pan B, Lee JJH, Lum JJ, Lim CYY, YeoIKX, Wong CJY, Liu M, Oh JLL, Chia CPL, Loh CH, Chen A, Chen Q, Weissman IL, Loh KM, Lim B. A Roadmap for Human Liver Differentiation from Pluripotent Stem Cells. Cell Rep. 2018 Feb 20;22(8):2190-2205. doi: 10.1016/j.celrep.2018.01.087. PMID: 29466743; PMCID: PMC5854481.

  4. Tan AKY, Loh KM, Ang LT. Evaluating the regenerative potential and functionality of human liver cells in mice. Differentiation. 2017 Nov-Dec;98:25-34. doi: 10.1016/j.diff.2017.09.003. PMID: 29078082.