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Albert Einstein College of Medicine of Yeshiva University eighth annual Marshall S. Horwitz, M.D. Faculty Prize for Research Excellence presented to Pamela Stanley, Ph.D. march 31, 2014 4:00 p.m. Robbins Auditorium Leo Forchheimer Medical Science Building Marshall S. Horwitz, M.D. Faculty Prize for Research Excellence Program Welcome Allen M. Spiegel, M.D. The Marilyn and Stanley M. Katz Dean Remarks from the Selection Committee Chair Vinayaka R. Prasad, Ph.D. Professor, Microbiology & Immunology Remembering Marshall S. Horwitz, M.D. Stephen G. Baum, M.D. Senior Associate Dean for Students Professor, Medicine; Microbiology & Immunology Introduction of Pamela Stanley, Ph.D. Arthur I. Skoultchi, Ph.D. Professor and Chair, Cell Biology Judith and Burton P. Resnick Chair in Cell Biology The Marshall S. Horwitz, M.D. Faculty Prize Lecture “Glycans that Regulate Development and Notch Signaling” Pamela Stanley, Ph.D. Professor, Cell Biology The Horace W. Goldsmith Foundation Chair Presentation of the Marshall S. Horwitz, M.D. Faculty Prize for Research Excellence Allen M. Spiegel, M.D. Reception Pamela Stanley, Ph.D. Pamela Stanley is a pioneer in the field of glycobiol- ogy, the study of the carbohydrate (sugar) molecules that are attached to proteins and lipids in all organisms. These attached sugars, linked to form glycans, play crucial roles in many biological processes, including cell signaling (many cell-surface receptors, for example, are glycoproteins), embryonic development and the growth, fate and migration of cells. Many disease-causing microbes use cell-surface receptor glycans to initiate infection of cells. Dr. Stanley obtained her Ph.D. in the department of microbiology at the University of Melbourne in her native Australia, where she studied the assembly of the influenza virus (a very hot field at the time). She was then offered a postdoctoral fellowship by the Medical Research Council in Canada to work in the University of Toronto laboratory of Dr. Louis Siminovitch, chair of medical genetics and a pioneer in the new field of somatic cell genetics. There she isolated rare mutant Chinese hamster ovary (CHO) cells that had somehow survived a lethal dose of ricin, the infamous plant toxin found in castor beans. That work introduced her to glycosylation—a main focus of her glycobiology research today. Glycosylation is the process by which enzymes called glycosyltransferases attach simple sugars to growing carbohydrate molecules called glycans; these glycans are covalently attached to proteins and lipids to form glycoproteins and glycolipids, respectively. Working with Dr. Harry Schachter in Toronto, Dr. Stanley found that the first of the mutant hamster ovary cell lines she studied, known as Lec1, survived ricin because a glycosyltransferase responsible for adding a specific sugar to glycoprotein cell-surface receptors was mutated, preventing ricin from binding to and killing Lec1 cells. Dr. Stanley later developed mutant CHO cell lines containing a variety of defective glycosyltransferases. She brought them to Einstein in 1977, when she was recruited by Dr. Matthew Scharff to join the department of cell biology. She has used those mutant cell lines to study how glycosyltransferases affect the structure and function of cell-surface receptors. Such mutations are by no means limited to hamsters; in fact, scientists have now identified about 100 congenital disorders of glycosylation in humans, several of which can be studied in mutant CHO and mouse cell lines developed by the Stanley lab. Dr. Stanley was promoted to associate professor in 1982 and full professor in 1986 and received tenure in 1989. In 2007, she was appointed the Horace W. Goldsmith Foundation Chair. She is a long-standing member of the Albert Einstein Cancer Center, has served as program leader of the Molecular Membrane Biology Group since 1988 and was appointed associate director for laboratory research of the cancer center in 2002. In recent years, the Stanley lab has discovered how several different glycans influence embryonic development, female and male reproduction and cancer progression. Dr. Stanley and her colleagues have found, for example, that specific parts of certain glycans are required for spermatogenesis, are important for oogenesis, regulate growth factor signaling and retard tumor progression. A particularly exciting discovery involved one of the most important cell-surface receptors in all of biology: the Notch receptor, which plays a key role in sending signals that control the growth and fate of cells (whether, for example, they’ll proliferate or undergo differentiation to a new cell type). A protein called Fringe was known to direct Notch signaling during embryonic development, profoundly affecting the way the skeleton is organized in mammals. In collaboration with labs at Princeton and Stony Brook, Dr. Stanley discovered the mechanism by which Fringe controls Notch signaling by functioning as a glycosyltransferase. Dr. Stanley has published more than 150 peer-reviewed papers and reviews with students, postdocs and collaborators, and she has written numerous invited reviews and chapters. She is an editor of the textbook Essentials of Glycobiology, second edition, and has served as a permanent member of one American Cancer Society and two National Institutes of Health study sections. She also has served or is serving on the editorial boards of Molecular and Cellular Biology, the Journal of Biological Chemistry, Molecular Biology of the Cell, Glycobiology and the Glycoconjugate Journal, and she is a reviewer for a wide variety of scientific journals. Dr. Stanley has received numerous honors for her research excellence, including a MERIT award from the National Cancer Institute, the Karl Meyer Award of the Society for Glycobiology and the major award of the International Glycoconjugate Organization. In addition, she is a past president of the Society for Glycobiology and has organized several international meetings. At Einstein, she directed the Cell, Molecular Biology and Genetics training program from 1994 to 2007, has been elected to the Davidoff Society for excellence in medical school teaching and has received the LaDonne H. Schulman Award for Excellence in Teaching. Marshall S. Horwitz, M.D. 1937–2005 D r. Marshall Horwitz was a physicianscientist who was instrumental in advancing the understanding of the biology of the adenovirus, first by describing the outer protein of the virus and then by developing a method for replicating its DNA. These findings have proven crucial in offering researchers a system for studying adenovirus biology and using it in gene therapy. He explored how adenovirus genes help the virus evade the body’s immune surveillance system and how those viral genes could be used to “turn off ” the autoimmune reaction that leads to type 1 diabetes. In a paper published in 2008 in Gene Therapy, Einstein scientists used Dr. Horwitz’ strategy (and honored him as a co-author) in transplanting insulinproducing (beta) pancreatic cells into diabetic mice; the transplanted cells normalized glucose control while causing only a minimal immune response in the recipients. Whether in the laboratory or in a clinical setting, Dr. Horwitz led by an example that conveyed integrity, compassion and scholarship. His leadership was apparent in many facets of the medical school. He was instrumental in establishing the research program for the department of pediatrics, played a major role in Einstein’s Medical Scientist Training Program, was an associate director of the Albert Einstein Cancer Center and, as chair since 1991, led the department of microbiology & immunology into the 21st century. Through his nearly four decades of service to Einstein, his commitment to students went well beyond mentoring, and he was recognized by students and house staff with numerous awards and honors throughout the years. These included election to the Leo Davidoff Society, designation as an honorary alumnus of the College of Medicine’s Alumni Association, honorary membership in Alpha Omega Alpha and receipt of the Lewis M. Fraad House Staff Teaching Award. His extraordinary kindness and warmth, generosity, gentle spirit and scientific curiosity are all part of his treasured legacy. Marshall S. Horwitz, M.D. Faculty Prize for Research Excellence