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Our laboratory at the Stanford Institute for Stem Cell Biology & Regenerative Medicine and the Department of Developmental Biology aspires to understand how different human cell-types develop from stem cells, and how developing tissues incipiently take shape and form. To this end, we have delineated a comprehensive roadmap that describes how embryonic stem cells can develop into a spectrum of over twenty different human cell types. This roadmap enabled us to generate rather uniform populations of human liver progenitors, bone progenitors and heart progenitors from embryonic stem cells, each of which could regenerate their cognate tissue upon injection into respective mouse models. This platform to produce these engraftable human tissue progenitors provides fundamental building blocks for regenerative medicine and provides an ideal venue to understand human developmental biology. In particular we are interested in questions regarding cellular signaling, developmental competence and tissue organization.Kyle received his B.A. from Rutgers University, interned with Bing Lim at the Genome Institute of Singapore, and received his Ph.D. from Stanford University (working with Irving Weissman), with fellowships from the Hertz Foundation, the National Science Foundation and the Davidson Institute of Talent Development. He then continued research as the Siebel Investigator at the Stanford Institute for Stem Cell Biology & Regenerative Medicine, and later, as an Assistant Professor of Developmental Biology and The Anthony DiGenova Endowed Faculty Scholar. Kyle is a Packard Fellow, Pew Scholar, Human Frontier Science Program Young Investigator and Baxter Foundation Faculty Scholar, and his research has been recognized by the NIH Director's Early Independence Award, Forbes 30 Under 30, Harold Weintraub Graduate Award, Hertz Foundation Thesis Prize and the A*STAR Investigatorship.
Embryonic stem cells can produce any type of human cell in a dish. Thus they afford an opportunity to recreate, and thus study, basic developmental phenomena (lineage diversification, tissue self-organization and multilineage competence) that are difficult to probe in a developing embryo. However, this opportunity has yet to be fully realized because stem-cell differentiation often yields heterogeneous mixtures of cells that are ill-suited for molecular analysis or cell therapy.We have developed a reductionist system to define the minimal essential inductive and repressive signals necessary for the developmental induction of a given embryonic lineage from differentiating ESCs. These efforts culminated in systematic roadmaps describing the extrinsic signals that guide human ESCs into a variety of endoderm and mesoderm germ layer derivatives (including liver, intestinal, bone and heart progenitors) through a series of bifurcating intermediate steps. The overarching goal is to exploit the resultant highly-pure populations of human tissue progenitors to explore classic questions in developmental biology, using stem-cell differentiation as a technological platform.