Kotaro Sasaki MD, PhD

I am a physician-scientist and anatomic pathologist whose research focuses on development and pathophysiology of urogenital and reproductive organ systems. My principal research interests lie in elucidating the cellular and molecular mechanisms that orchestrate development of the urogenital organ system and eventually applying such knowledge for cellular and tissue reconstitution in vitro. Over the last 10 years, my research interest has focused on understanding the molecular pathways regulating the early development of human germ cells, gonadal somatic cells and the adrenocortical cells through combinatorial histologic, genomic and stem-cell-based approaches. I received clinical training as an anatomic pathologist at the University of Pittsburgh and the University of Washington, where I nurtured a broad knowledge base of human pathophysiology, particularly on the urogenital organ system. After completion of my clinical training, I pursued my postdoctoral fellowship in the Mitinori Saitou lab studying developing germ cells in humans and non-human primates using single cell genomics and stem cell-based approaches, which greatly improved our understanding of human germ cell development (published in Cell Stem Cell 2015 and Dev Cell 2016).

I established my own research group as an assistant professor at the University of Pennsylvania in late 2018. Since then, my laboratory has already made major achievements in two arenas. First, we determined how to successfully reconstitute human prospermatogonial development using human iPSCs. Second, we performed high-resolution spatial and temporal mapping of the gonadal and adrenocortical lineages in mice, monkeys and humans using single cell transcriptomic and histologic analyses, thus providing a molecular framework for understanding human adrenal disorders. Moreover, these data provide critical mechanistic insight for reconstitution of the adrenocortical lineage in vitro, as proposed in this application. In fact, this archive of in vivo human data allowed us to validate, in an unbiased manner, that the transcriptome of human iPSC-derived fetal adrenal organoids closely resembles that of the fetal zone in the human fetal adrenal cortex (Dev Cell 2022). This proposal will extend these studies and build higher order structural adrenocortical organization, which allows self-sustaining functionality in both in vivo and in vitro thereby has broad and long-lasting impact on therapeutics of adrenal diseases and endocrinology.

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