James E. Rothman, Ph.D., the Fergus F. Wallace Professor of Biomedical Sciences, chair of the Department of Cell Biology, professor of chemistry, and director of the Nanobiology Institute on Yale’s West Campus, is one of three winners of the 2013 Nobel Prize in physiology or medicine.
Rothman is one of the world’s foremost experts on membrane trafficking, the means by which proteins and other materials are transported within and between cells. The prize highlights his contributions to the understanding of exocytosis, a form of trafficking in which spherical sacs called vesicles fuse with cell membranes to deliver their contents outside the cell.
“This is fitting recognition of Jim Rothman’s brave, important, creative scientific research,” said Yale University President Peter Salovey, Ph.D., the Chris Argyris Professor of Psychology. “Yale is absolutely thrilled to have one of our most distinguished faculty—who is also one of our most distinguished alumni—receive this great honor.”
Exocytosis is ubiquitous in biology—it is essential to cell division and insulin secretion, for example—but it plays a particularly crucial role in the nervous system. In neurons, vesicles carrying neurotransmitters fuse with cell membranes at synapses, emptying their cargo to pass on the chemical messages that govern movement, perception, cognition, memory, and mood. For three decades, Rothman has performed biochemical and cell biology experiments that have revealed the molecular machinery of membrane trafficking in fine detail. Much of this work was done using a “cell-free” approach, in which Rothman sidestepped the complexities of working with complete cells by isolating the intracellular components crucial to membrane trafficking. This strategy allowed him to propose that complexes of membrane-associated proteins called SNAREs are required for vesicles to fuse with membranes.
“Jim Rothman is one of the most brilliant researchers of our time,” says Robert J. Alpern, M.D., dean and Ensign Professor of Medicine. “When he started his career, a number of successful biochemists were recognizing the importance of studying molecular processes in cell-free systems, but no one imagined that you could study vesicle trafficking in a cell-free system. Jim had the courage to try and the skills to succeed, and this bold approach revolutionized the field.”
Rothman shares the prize with Randy W. Schekman, Ph.D., of the University of California−Berkeley, and Thomas Südhof, M.D., of Stanford University. While at the University of Texas Southwestern Medical Center, Südhof discovered synaptotagmin, a protein in vesicle membranes that senses intracellular calcium levels. When a neuron is stimulated, calcium binds to synaptotagmin, which prompts the vesicle to release its contents by interacting with SNARE complexes and fusing with the cell membrane. Schekman discovered a set of genes required for vesicle traffic.
In 2002 Rothman and Schekman received the Albert Lasker Award for Basic Medical Research and the Louise Gross Horwitz Prize of Columbia University. In 2010 Rothman, Südhof, and Richard H. Scheller, Ph.D., were jointly awarded the Kavli Prize in Neuroscience.
In addition to grants from federal agencies, Rothman’s research has benefited from the long-term support of the G. Harold and Leila Y. Mathers Charitable Foundation.
Rothman graduated summa cum laude from Yale College in 1971, and earned a Ph.D. in biological chemistry from Harvard Medical School in 1976. After a postdoctoral fellowship in the lab of biochemist Harvey F. Lodish, Ph.D., at the Massachusetts Institute of Technology, he served on the faculties at Stanford School of Medicine, Princeton University, Memorial Sloan-Kettering Cancer Center and the Sloan-Kettering Institute in New York, and, most recently, Columbia University’s College of Physicians and Surgeons, where he was professor of physiology and biophysics, the Clyde and Helen Wu Professor of Chemical Biology, and director of the Columbia Genome Center.