James E. Rothman, Ph.D., one of the world’s foremost experts on membrane trafficking, the means by which proteins and other materials are transported within and between cells, has been named the Fergus F. Wallace Professor of Biomedical Sciences and chair of the School of Medicine’s Department of Cell Biology. Rothman will come to Yale from Columbia University’s College of Physicians and Surgeons, where he is now a professor in the Department of Physiology and Biophysics, the Clyde and Helen Wu Professor of Chemical Biology and director of the Columbia Genome Center.
In addition to directing Cell Biology, Rothman is the first recruit to Yale’s recently opened West Campus in West Haven, Conn., where he will launch a Center for High-Throughput Cell Biology. At the new center, multidisciplinary teams of scientists will develop tools and techniques to rapidly decipher the cellular functions of the 25,000 known protein-coding genes in the human genome, providing fresh insights into disease and new molecular targets for therapy. Under Rothman’s leadership the Department of Cell Biology will be significantly expanded, and will be co-located at the West Campus along with its present location at the main campus of the School of Medicine.
For his decades of seminal research on the transport of molecules between intracellular compartments and across cell membranes, Rothman has received numerous honors, including Columbia’s Louisa Gross Horwitz Prize and the Lasker Award for Basic Medical Research, two prizes that are sometimes colloquially referred to as “pre-Nobels” because so many recipients of the Horwitz and Lasker awards have gone on to become Nobel laureates. Much of this work was done using a “cell-free” approach, in which Rothman isolated intracellular components crucial to molecular transport in a laboratory dish. This strategy allowed him to perform elegant, focused experiments that sidestepped the complexity of working with complete cells.
“Jim Rothman is one of the most brilliant researchers of our time,” said Robert J. Alpern, M.D., dean and Ensign Professor of Medicine. “When Jim 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. Jim continues to bring this combination of brilliance and intensity to his research, and now also to the continued development of an exceptional cell biology department.”
Carolyn W. Slayman, Ph.D., Sterling Professor of Genetics and deputy dean of academic and scientific affairs, added, “Jim Rothman has helped to shape the field of cell biology over the past two decades, and it will be exciting to have him join the scientific community at Yale.”
Rothman has many personal and scientific connections to Yale. He graduated summa cum laude from Yale College in 1971 with a degree in physics, and conducted research as an undergraduate in Yale’s Department of Molecular Biophysics and Biochemistry with Eugene Higgins Professor Donald M. Engelman, Ph.D. (then an assistant professor) and Harold J. Morowitz, Ph.D., now Clarence J. Robinson Professor of Biology and Natural Philosophy at George Mason University in Fairfax, Va.
Both of Rothman’s children are Yale College graduates, and his spouse, Joy Hirsch, Ph.D., is a former professor at Yale School of Medicine who now directs the Program for Imaging and Cognitive Sciences at Columbia University.
“My life’s work on membrane trafficking in cells was inspired by the discoveries of George Palade, who founded Yale’s cell biology department in 1973, and indeed founded the field of cell biology as we know it today,” Rothman said. “It is a privilege to lead the department he began as we redefine molecular cell biology and catalyze its impact on medicine, and a unique pleasure to return to Yale.”
George E. Palade, M.D., a Nobel Prize-winning cell biologist, led Yale’s department for its first decade and established its current directions. Beginning in the 1950s, electron microscope images made by Palade and other scientists revealed that tiny spherical sacs known as vesicles encapsulate and shuttle proteins, hormones, neurotransmitters and other substances between intracellular organelles and to the cell surface. In these micrographs, vesicles were seen to fuse with membranes, spilling their contents into intracellular organelles, or, in the case of the membrane at the cell surface, into the extracellular space, where the released vesicular cargo could interact with neighboring cells or enter the bloodstream to affect distant ones. This latter process, known as exocytosis, is basic to life and occurs in organisms as diverse as yeast and humans; in our own case, exocytosis underlies physiological functions ranging from the secretion of insulin to the regulation of the brain neurotransmitters responsible for movement, perception, memory and mood. Rothman discovered the molecular mechanisms and machinery responsible for these and related processes.
After graduating from Yale, and basic science training as a medical student at Harvard Medical School (HMS), Rothman soon resolved to learn more about the mechanisms of vesicular transport. He shifted his focus to basic science, earning a Ph.D. in biological chemistry from HMS in 1976. He then spent two years as a postdoctoral associate in the laboratory of Harvey F. Lodish, Ph.D., a preeminent biochemist at the Massachusetts Institute of Technology.
In 1978, Rothman moved to the Department of Biochemistry at Stanford School of Medicine as an assistant professor. At this time, he and Randy W. Schekman, Ph.D., of the University of California, Berkeley, conducted parallel research programs, using biochemical and genetic techniques to identify and characterize the proteins that are necessary for vesicle transport, and for the docking and fusion of vesicles with membranes. For this early work, Rothman and Schekman have shared many awards.
Rothman continued his research at Princeton University from 1988 until 1991, when he became the founding chair of the Department of Cellular Biochemistry and Biophysics at Memorial Sloan-Kettering Cancer Center in New York as well as vice chair of the Sloan-Kettering Institute.
In 1993, Rothman discovered a complex of vesicle membrane proteins that he implicated in membrane fusion, and based on this discovery he formulated the “snare hypothesis,” which has become highly influential in the study of membrane trafficking.
This hypothesis posits that distinctive, complementary protein complexes known as snares, expressed on both vesicles and target membranes, first ensure that different classes of vesicles bind to appropriate membranes and then unleash biochemical changes leading to fusion of vesicles with those membranes and the delivery of the vesicles’ cargo to its proper destination.
Rothman has given invited lectures on his work throughout the world, and has served on the editorial boards of Science and Cell.
He is a member of the National Academy of Sciences and the Institute of Medicine, a fellow of the American Academy of Arts and Science, and a foreign associate of the European Molecular Biology Association.
Rothman succeeds Ira Mellman, Ph.D., a distinguished cell biologist and immunologist who was chair and Sterling Professor of Cell Biology at the School of Medicine until 2007, when he joined the biotechnology company Genentech as vice president for oncology research.
Since Mellman’s departure last year, former chair James D. Jamieson, M.D., Ph.D., professor of cell biology and director of the medical school’s M.D./Ph.D. Program, has served as interim chair of the Department of Cell Biology.