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Changing
Course at the Graduate School Summer
1998 Thomas Appelquist's five-year-term as dean of the Graduate School was not the easiest of assignments. The academic job market for recent PhDs has long been poor in many disciplines; federal support for graduate research, though substantial, is shaky; and a highly vocal group of teaching assistants, who felt that their work was undervalued by the University, engaged in an often rancorous campaign to form a graduate student union. While the dean has, by most accounts, dealt well with these and other challenges, no one was surprised when Appelquist, the Eugene Higgins Professor of Physics, announced last year that he would return to teaching and research rather than seek another term. Appelquist's successor is Susan Hockfield, a professor of neurobiology at the School of Medicine, who assumed her duties July 1 as the 17th dean in the Graduate School's 151-year history. "This is a wonderful opportunity and a privilege," says Hockfield, who was director of graduate studies in neurobiology from 1986 to 1994 and has written more than 90 scientific papers and review articles on the biology of the nervous system. Hockfield is the first member of the Medical School faculty to head the Graduate School, and her appointment is seen by at least some observers as an example of the increasing links between the graduate and professional sectors of the University. "Neuroscience embraces many disciplines," says Hockfield, who helped develop the new and collaborative graduate program in the biological and biomedical sciences. (The new dean, in addition to managing the Graduate School's 2,300 students and 65 departments and programs, will also be responsible for overseeing faculty appointments and promotions in the natural and social sciences.) "I'm very pleased for Yale," says longtime colleague James D. Watson, the winner, along with Francis Crick and Maurice Wilkins, of the 1962 Nobel Prize in Physiology or Medicine for discovering the structure of DNA. "Susan knows what it takes to keep the University competitive." Watson, president of the internationally known Cold Spring Harbor Laboratory (CSHL) on Long Island, hired Hockfield as a junior staff investigator in 1980 and has worked with her ever since. "Susan quickly became absolutely indispensable," notes Watson, who, when Hockfield joined the Yale faculty in 1985, ensured that the researcher would remain part of CSHL by appointing her director of its prestigious summer program in neurobiology. (She held that position until last year and remains a consultant to the laboratory.) "We have all benefited from her common sense, high character, and intelligence. Simply put, she gets things done." Hockfield's recent work tackles a medical mystery: why a malignant brain tumor called a glioma is so deadly. "Gliomas are a therapeutic nightmare because the cells are highly mobile," she explains. A number of forms of cancer can spread from a primary site in say, the breast or the lung, migrate, and take root in the brain. But typically, the resulting tumors are relatively compact and self-contained and so are amenable to treatment by such means as surgery or radiation. The cells that give rise to gliomas, however, originate in the brain, invade the surrounding brain tissue, and are constantly on the move. There's very little physicians can do, and frequently, the patient is dead within a year. That may change. In a paper published in April in the Journal of Neuroscience, Hockfield and her Yale research team present the first clear explanation of genetic and molecular methods glioma cells may use to overwhelm the brain. This investigation of basic cellular biology offers tantalizing strategies for therapy, she says, and it shows how many scholarly endeavors result from both directed work and serendipity. Hockfield, who is 47, started down this path early. "I've been interested in biology from the time I was 5 or 6, I was good at math and science, and it never occurred to me that there was something I couldn't do," she notes. Her parents encouraged her to pursue her interests, and so did her teachers. At the University of Rochester, Hockfield immersed herself in the study of cell biology and graduated in 1973, a semester early. "I was advised by an insightful professor to get a job in a laboratory, and fortuitously, I was hired as a lab technician in neuroscience. Quickly, I realized that this was what I'd been looking for all my life," she says. After a couple of years, Hockfield enrolled at Georgetown University's School of Medicine, but not to become a physician, as she'd once planned. Instead, she pursued a doctorate in anatomy. Hockfield spent most of her time working in the laboratories of the National Institutes of Health, where she was part of a team investigating the pathways in the nervous system through which pain is perceived and processed. Her adviser there was Steven Gobel, and both he and the setting had a profound influence on Hockfield's life and her view of graduate education. "You were immediately treated like a scientist, and Steve was wonderfully generous with his time and expertise," Hockfield recalls of her mentor. "He had an awe about the beauty of the nervous system, and we talked science all the time." Of course, the Graduate School that Hockfield now leads trains scholars in the arts and the sciences, but as she sees it, there are two aspects of the "transformation by which a student comes in as a student and emerges as a colleague" that, regardless of one's scholarly discipline, are "absolutely key" to the process: collegiality, and a passion for research and teaching. "I'm enthusiastic about scholarship of all sorts, whether it's a discovery about the fate of the universe or a new way to interpret a text," says Hockfield, adding that although the methodologies may differ, "the stories we tell -- and that we're training the next generation of scholars to discover -- are always woven from disparate pieces of data. Figuring out how to piece these together is the very core of our enterprise." The new dean's own research story "certainly didn't come written out on a petri dish," she admits. In the course of her graduate training, she developed expertise in electron microscopy with an eye toward building a taxonomy of the nerve cells, most of which looked alike, that were involved in pain processing. It was arduous work, but in the early 1980s, biologists developed what are called monoclonal antibodies. These molecules can zero in on highly specific sites on cells, and with the electron microscope, Hockfield could see precisely where the antibodies were going. "We had a powerful new tool with which we were discovering molecular differences between neurons," she says. "What did all this variation mean?" James Watson wondered as well, and he hired her to work on the problem at Cold Spring Harbor, a place she dubbed a "wonderland for science." CSHL, Hockfield explains, is devoted to research and training in "absolutely cutting edge science and technology." In her eventual role as director of the lab's summer neuroscience program, she recruited faculty, secured research funding, and helped develop courses that provided state-of-the-art training to close to 200 students each year. In this heady environment, people ate, drank, and slept research, and here Hockfield found her "life's work: discovering how the molecular elements of the nervous system change over the course of development." Of particular interest were the changes during development that take place in the chemical makeup of the extracellular matrix, the space between each nerve cell. Hockfield continued this line of research when she came to Yale in 1985, and as she chronicled the brain's strict construction sequence that begins when a layer of proliferative cells give rise first to neurons and then to a support structure made up of glial cells, she observed something intriguing. When the glial cells are being created, the extracellular matrix is awash in BEHAB -- brain-enriched hyaluronan binding protein. The only other time BEHAB is abundant is when a glioma in running rampant. In a real sense, Hockfield had been primed for making the transition from basic biology to tumor research by dinner-time conversation. Her husband, Thomas Byrne (they have a six-year-old daughter, Elizabeth), is a neuro-oncologist at Yale-New Haven Hospital and a clinical professor at the Medical School. "We often talked about gliomas and wondered why they were invariably fatal," she says. One key appears to lie in the tumor's uncanny ability to turn on the nascent gene that makes BEHAB, the protein that plays a critical role in the glial cell's ability to proliferate and move during the course of normal development. "Our experiments indicate that this molecule can mediate the invasiveness of gliomas," says Hockfield, whose group is now looking at ways of either turning off the BEHAB gene or preventing the protein from being activated by enzymes. In assuming the deanship, the task of ensuring that current and future generations of graduate students will continue to have the opportunities she has enjoyed may mean her own scientific work will slow down. But it won't stop, says Hockfield, stressing the critical role of research. Says the new dean: "A vibrant scholarly enterprise is what the University is all about." |
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Yale
Alumni Magazine, PO Box 1905, New Haven, CT 06509-1905. USA.
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