Kyle M Loh, Assistant Professor of Developmental Biology
Research Description: Our 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. We have 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 our research is rooted in basic developmental and stem cell biology, we welcome and enjoy interactions with those interested in basic, translational and clinical science.
Currently, we are investigating two areas that might see utility in future strategies to treat Type 1 Diabetes. First, we 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, we 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.
Selected relevant publications (Stanford DRC members are in BOLD):
- Loh KM*, Ang LT*, Zhang J**, Kumar V**, Ang J, Auyeong JQ, Lee KL, Choo SH, Lim CYY, Nichane M, Tan J, Noghabi MS, Azzola L, Ng ES, Durruthy-Durruthy J, Sebastiano V, Poellinger L, Elefanty AG, Stanley EG, Chen Q, Prabhakar S, Weissman IL, Lim B (2014). Efficient endoderm induction from human pluripotent stem cells by logically directing signals controlling lineage bifurcations. Cell Stem Cell 14: 237-52 (*co-first author), PubMed 24412311
- Loh KM*, Chen A*, Koh PW, Deng T, Sinha R, Tsai JM, Barkal AA, Shen KY, Jain R, Morganti RM, Ng SC, Fernhoff NB, George BM, Wernig G, Salomon RAE, Chen Z, Vogel H, Epstein JA, Kundaje A, Talbot WS, Beachy PA, Ang LT†, Weissman IL† (2016). Mapping the pairwise choices leading from pluripotency to human bone, heart, and other mesoderm cell types. Cell 166: 451-67 (*co-first author),PubMed 27419872