Sean J. Morrison
The University of Texas Southwestern Medical Center
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Primary Section: 41, Medical Genetics, Hematology, and Oncology Secondary Section: 22, Cellular and Developmental Biology Membership Type:
Member
(elected 2020)
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Biosketch
Sean Morrison is stem cell biologist who studies the cellular and molecular mechanisms that regulate stem cell function and the role these mechanisms play in cancer. His laboratory discovered key mechanisms that regulate stem cell self-renewal as well as the location and cellular composition of niches for hematopoietic stem cells in adult blood-forming tissues. Dr. Morrison was born in Halifax, Nova Scotia and completed a BSc in biology and chemistry at Dalhousie University in 1991. He completed a PhD in immunology at Stanford University in 1996 and a postdoctoral fellowship in neurobiology at Caltech in 1999. Dr. Morrison is a Howard Hughes Medical Institute Investigator (since 2000) and is the founding Director of Children’s Research Institute at the University of Texas Southwestern Medical Center (since 2011). He was elected to the National Academy of Medicine in 2018 and the National Academy of Sciences in 2020. Dr. Morrison served as the President of the International Society for Stem Cell Research (2015-16) and has been active in public policy work related to stem cell research, testifying before the U.S. Congress and serving as a leader in the successful “Proposal 2” campaign to protect stem cell research in Michigan’s state constitution (2008).
Research Interests
We study the intrinsic and extrinsic mechanisms that regulate stem cell self-renewal (particularly in the hematopoietic system) and the role these mechanisms play in cancer (particularly leukemia and melanoma). Self-renewal is the process by which stem cells divide to make more stem cells, perpetuating stem cells throughout life to regenerate tissues. We discovered a series of key regulators that distinguish stem cell self-renewal from the proliferation of restricted progenitors in the same tissues. We also identified ways in which self-renewal mechanisms change with age, conferring temporal changes in stem cell properties that match the changing growth and regeneration demands of tissues. In terms of cell-extrinsic mechanisms, we identified the location and cellular composition of hematopoietic stem cell (HSC) niches in adult bone marrow and spleen, and discovered the Leptin Receptor+ perivascular stromal cells that are the major source of factors required for HSC maintenance in the bone marrow. We have shown that HSCs are metabolically distinct from restricted progenitors in vivo and depend upon metabolic regulation for epigenetic control and leukemia suppression. We discovered that distant metastasis by melanoma cells is limited by oxidative stress and that successfully metastasizing melanoma cells undergo reversible metabolic changes to cope with oxidative stress. We proposed that “pro-oxidant” therapies that exacerbate oxidative stress in cancer cells could be used to inhibit cancer progression.
