Download P S .D. Marshall S. Horwitz, M.D. Faculty Prize

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