Kyle Loh

Kyle M Loh, PhD, Assistant Professor, Department of Developmental Biology, Stanford University School of Medicine; The Anthony DiGenova Endowed Faculty Scholar

Research Description: Dr. Loh’s overarching goal is to understand how tissues develop and to use this knowledge to differentiate human pluripotent stem cells (hPSCs, including embryonic and induced pluripotent stem cells) into pure populations of various cell-types. Current efforts to differentiate stem cells often generate an impure mixture of cell-types that are poorly suited for use in basic research or regenerative medicine. Loh has developed new strategies to precisely differentiate hPSCs into pure populations of a desired cell-type, in part by blocking the formation of unwanted cell-types. While his research is rooted in basic developmental and stem cell biology, his team has interactions with those interested in basic, translational and clinical science. 

Currently, his group is investigating two areas that might see utility in future strategies to treat Type 1 Diabetes. First, they are attempting to generate blood-forming (hematopoietic) stem cells from hPSCs. If this were successful, transplantation of these genetically-normal, hPSC-derived blood stem cells into an autoimmune patient could potentially replace their diseased immune system with a healthy one, thus preventing or ameliorating Type 1 Diabetes. This strategy would involve collaborations with others to define biomarkers of Type 1 Diabetes development (before it becomes clinically manifest) and ways to safely condition patients to accept foreign blood stem cells. Second, they have developed a general method to rapidly generate pure populations of definitive endoderm (the developmental precursor to the pancreas) from hPSCs. The ability to generate pure endoderm populations should facilitate the subsequent manufacture of pancreatic progenitors and eventually, islet cells, from hPSCs, which could be useful for restoring islet mass in Type 1 diabetic patients. He works with other SDRC members and colleagues at UCSF in the JDRF Northern California Center of Excellence. Dr. Loh also serves as co-leader of the SDRC “Immunology, Transplantation and Stem Cells in Diabetes” research affinity group. 

Selected relevant publications (Stanford DRC members are 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. George BM, Kao KS, Kwon HS, Velasco BJ, Poyser J, Chen A, Le AC, Chhabra A, Burnett CE, Cajuste D, Hoover M, Loh KM, Shizuru JA, Weissman IL. Antibody Conditioning Enables MHC-Mismatched Hematopoietic Stem Cell Transplants and Organ Graft Tolerance. Cell Stem Cell. 2019 Aug 1;25(2):185-192.e3. doi: 10.1016/j.stem.2019.05.018. PMID: 31204177; PMCID: PMC6679784. 

  3. Wilkinson AC, Ishida R, Kikuchi M, Sudo K, Morita M, Crisostomo RV, Yamamoto R, Loh KM, Nakamura Y, Watanabe M, Nakauchi H, Yamazaki S. Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature. 2019 Jul;571(7763):117-121. doi: 10.1038/s41586-019-1244-x. PMID: 31142833; PMCID: PMC7006049. 

  4. Ang LT, Tan AKY, Autio MI, Goh SH, Choo SH, Lee KL, Tan J, Pan B, Lee JJH, Lum JJ, Lim CYY, Yeo IKX, 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.