|
Spotlight
on Dr. Lorraine J. Gudas
Dr.
Lorraine J. Gudas is the Revlon Pharmaceutical Professor of Pharmacology
and Toxicology and Chairman of the Department of Pharmacology,
Weill Medical College and Graduate School of Medical Sciences
of Cornell University. Her work is focused on understanding the
molecular actions of vitamin A (retinol) in the regulation of
cell proliferation and cell differentiation. Dr. Gudas’s laboratory
was one of the first to identify "target genes" that respond to
the addition of vitamin A and/or its related metabolites, such
as retinoic acid, by increasing their rate of transcription, the
production of mRNA molecules from the gene template. Retinoic
acid interacts with intracellular proteins, the retinoic acid
receptors (RARs), to elicit its effects on its target genes and
thereby on cell differentiation. Because vitamin A regulates normal
cell differentiation and the process of carcinogenesis is often
associated with defects in cell differentiation, higher pharmacological
doses of vitamin A have been utilized to augment the intracellular
levels of vitamin A in premalignant cells, thereby inhibiting
the development of some types of cancers. Retinoic acid is also
currently used in the treatment of some types of cancer, including
renal cancer and acute promyelocytic leukemia.
As
the RARs (RARa, RARb, RARg) appear to play key roles in the mediation
of vitamin A and retinoic acid action, it is reasonable to assume
that the cancer preventive actions of retinoids are also mediated
by the RARs. However, the expression of the various RAR types
changes during the progression of cells from the premalignant
to the malignant state. For instance, analyses of carcinomas of
various types by the Gudas laboratory and other laboratories have
revealed that the RARb gene, but not the RARa and RARg genes,
is frequently expressed at abnormally low levels in human squamous
cell carcinomas as compared to normal epithelial cells. Dr. Gudas's
laboratory is now focusing on understanding the mechanism by which
RARb gene expression is reduced during the process of carcinogenesis.
Her laboratory is also in the process of identifying specific,
key target genes of RARb. Drugs which maintain elevated levels
of RARb in normal and premalignant cells could then be used as
cancer chemopreventive agents. Alternatively, if the utility of
vitamin A and retinoic acid analogs as cancer prevention agents
is limited because of abnormalities in retinoic acid receptor
functions associated with the progression to malignancy, then
it should be possible instead to focus on key target genes of
the retinoic acid receptors, and in particular RARb, for the development
of cancer prevention agents in the future. The area of retinoid
pharmacology is currently very exciting and further research should
result in improved approaches for cancer prevention. In the future,
cancer preventive approaches, similar to those now accepted in
cardiovascular medicine to prevent disease, should become a reality.
Dr.
Gudas has held many positions in national organizations concerned
with cancer prevention and treatment. She was the Scientific Program
Director for the annual American Association for Cancer Research
(AACR) meeting in Washington, DC in 1996, attended by more than
8,000 researchers. From 1998 through 1999, she was the Chair of
the Charles F. Kettering Award Committee of the General Motors
Cancer Research Foundation. Dr. Gudas was also a member of the
National Cancer Institute's Cancer Centers and Program Projects
Parent Committee from 1995 through 1999. After serving a 3-year
term on the Board of Scientific Counselors of the National Heart,
Lung, and Blood Institute (NHLBI), Dr. Gudas was selected as the
Chair of this Board in 1999; her term as Chair ended in June 2001.
Her current work on behalf of the NHLBI involves membership on
the Data and Safety Monitoring Board for the "Feasibility of Retinoids
in the Treatment of Emphysema" (FORTE) clinical trials. After
serving as a Councilor, a member of the governing body of the
Association for Medical School Pharmacology (AMSP), from 1996-1998,
Dr. Gudas was elected Secretary of the organization in 2000. The
AMSP, an association of pharmacology department chairmen, sponsors
teaching workshops, continually revises and updates lists of drugs
for medical school teaching, and represents pharmacology within
the Association of American Medical Colleges. Dr. Gudas was later
elected in 2000 to a term on the AACR Board of Directors, and
was also honored by the AACR with its 1999 Women in Science Annual
Award for Scientific Achievement.
In
addition to her current and/or past membership on many national
committees, Dr. Gudas serves on numerous academic external advisory
or review boards for institutions including the University of
Vermont Cancer Center, the University of North Carolina at Chapel
Hill Lineberger Cancer Center, and the University of Maryland
Cancer Center. She was also a co-author on an article summarizing
trends and opportunities in cancer prevention research titled,
"Prevention of Cancer in the Next Millennium: Report of the Chemoprevention
Working Group of the American Association for Cancer Research"
(1).
- Alberts,
D.S., Colvin, O.M, Conney, A.H., Ernster, V.L., Garber, J.E.,
Greenwald, P., Gudas, L.J., Hong, W.K. (Co-Chairperson), Kelloff,
G.J., Kramer, R.A., Lerman, C.E., Mangelsdorf, D.J., Matter,
A., Minna, J.D., Nelson, W.G., V., Pezzuto, J.M., Prendergast,
F., Rusch, V.W., Sporn, M.B. (Co-Chairperson), Wattenberg, L.W.,
and Weinstein, I.B. Prevention of cancer in the next millennium:
report of the chemoprevention working group of the American
Association for Cancer Research. Cancer Res. 1999, 59: 4743-4758
|
