Sandra L. Schmid
Chan Zuckerberg Biohub
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Primary Section: 22, Cellular and Developmental Biology Secondary Section: 21, Biochemistry Membership Type:
Member
(elected 2020)
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Biosketch
Sandra Schmid is a cell biologist recognized for her work on the molecular mechanisms governing clathrin-mediated endocytosis (CME). She pioneered cell free assays for CME, established the mechanism by which the GTPase dynamin catalyzes membrane fission and discovered that CME can regulate sustained signaling by activated surface receptors and that downstream signaling can in turn, feedback to regulate CME. Schmid was born in Vancouver, B.C., obtained her Bachelor’s Degree in Cell Biology from the University of British Columbia and a Ph.D. in Biochemistry at Stanford in 1985. After a postdoctoral fellowship in cell biology at Yale, she joined the faculty of the Scripps Research Institute in 1988, rising to serve as Chair of Cell Biology from 2001-2011. In 2012 she moved to UT Southwestern to become Chair of Cell Biology, and in 2020, became the inaugural Chief Scientific Officer at Chan Zuckerberg Biohub. Schmid has provided important leadership to the scientific community as co-founding editor of Traffic, Editor in Chief of Molecular Biology of the Cell and as President of the American Society for Cell Biology.
Once considered a constitutive process that functions to terminate signaling by removing receptor tyrosine kinases from the surface (“down-regulation), Schmid established that clathrin-mediated endocytosis (. These discoveries emerged from long-standing efforts to define the molecular mechanism of endocytosis. Schmid pioneered the use of cell-free endocytosis assays for CME and defined biochemically distinct stages of clathrin-coated vesicle budding. Previously implicated from genetic studies in Drosophila, her work established a direct role for the GTPase dynamin in pinching off coated vesicles. Separately and collaboratively with De Camilli, Schmid provided the breakthrough mechanistic insight that dynamin assembles into rings that can constrict membranous necks to release budding vesicles. Subsequent extensive cell biological, biochemical, structural and biophysical studies by Schmid and her collaborators have elucidated the mechanistic underpinnings that govern this paradigmatic fission GTPase. Her more recent work establishes that in addition to its role in fission, dynamin regulates early stages of CME and functions at the nexus of reciprocal crosstalk between signaling and endocytosis.
Research Interests
Sandra Schmid’s laboratory studies the molecular underpinnings and regulation of clathrin-mediated endocytosis (CME). Using a combination of biochemistry, biophysics, molecular biology and live cell quantitative total internal reflection fluorescence microscopy they have shown that CME, once considered a constitutive process, is highly regulated and governed by an ‘endocytic checkpoint’. A myriad of endocytic accessory proteins govern the endocytic checkpoint and determine the rates and efficiencies of CME. They elucidated the paradigmatic mechanism of dynamin-catalyzed membrane fission and established that in addition to its role in fission, dynamin also regulates early stages of CME, in an isoform-specific manner. Earlier studies established that endocytic trafficking controls signaling downstream of receptor tyrosine kinases and G-protein coupled receptors. The Schmid lab has more recently shown the signaling pathways downstream of these receptors can in turn, regulate endocytic trafficking and that this crosstalk can be co-opted in cancer cells to enhance their metastatic capabilities.
