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Ann R. Kennedy
Richard Chamberlain Professor of Research Oncology, Dept of
Radiation Oncology
Cancer Biology Program
Address
195 John Morgan
Building
3620 Hamilton Walk
Philadelphia, PA 19104
Office tel.: 215 898-0079
Lab tel.: 215 898-5088, 0270, 0271
Fax: 215 898-0090
E-mail: akennedy@mail.med.upenn.edu
EDUCATION
Vassar College:
AB (Biology), 1969.
Harvard University: MSc(Radiation Biology), 1971.
Harvard University: DSc (Radiation Biology), 1973.
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Research Interests
- Biological effects of radiation, with emphasis on carcinogenesis
and cancer prevention.
Key words: Cancer,
proteases, protease inhibitors, prostate specific antigen
(PSA), cancer prevention, oncogenes, space program, gene expression,
ATR and Chk2, DNA repair.
Description of
Research
The research in this laboratory currently involves studies
on the mechanism(s) involved in the induction of malignant
transformation and its modification by various chemical agents
in both in vitro and in vivo systems; radiation and chemicals
are utilized as the carcinogenic agents in these studies.
The modifying agents being studied include both promoting
and suppressing agents for carcinogenesis, with emphasis on
agents modifying free radical reactions and protease inhibitors.
Studies on the mechanism of action of the protease inhibitor
suppression of carcinogenesis have focused on the effects
of these agents on the expression of specific oncogenes and
proteases thought to be involved in the conversion of a cell
to the malignant state. Human trials utilizing the soybean-derived
protease inhibitor, the Bowman-Birk inhibitor (BBI), as a cancer
chemopreventive agent are ongoing. Some of the current laboratory
work involves studies on the effects of BBI on surrogate endpoint
biomarkers (SEBs) of carcinogenesis in human tissue. Examples
of SEBs being studied include proteases, such as prostate specific
antigen (PSA), expression of certain oncogenes, etc. A major
new program in Space Radiation Biology has begun, with efforts
being made to protect astonauts against the expected biologic
effects of radiation encountered during space travel. This
program focuses on the ability of selenium compounds to prevent
and suppress the induction of cancer by radiation. For this
work, it is hypothesized that selenium triggers expression
and accumulation of ATR and Chk2 kinases that in turn regulate
early signaling elements in checkpoint pathways, namely Rad9-Hus1-Rad1
(9-1-1), induced by ionizing radiation produced DNA damage.
Selected Publications
Kennedy, A.R., Davis, J.G., Carlton, W. and
Ware, J.H. Effects of dietary antioxidant supplementation
on the development of malignant lymphoma and other neoplastic
lesions in mice exposed to proton or iron ion radiation. Radiation
Res. 169: 615-625, 2008.
Wambi, C., Sanzari, J., Wan, X.S., Nuth, M.,
Davis, J., Ko, Y.-H., Sayers, C.M., Baran, M., Ware, J.H.
and Kennedy, A.R. Dietary antioxidants protect hematopoietic
cells and improve animal survival following total body irradiation.
Radiation Res. 169(4): 384-96, 2008.
Stewart, J., Ware, J.H., Boysen, C., Gulati,
S., Zhou, Z., Rosenfeld, S., Kopelovich, L. and Kennedy, A.R.
Effects of selenomethionine on the gene expression profile
of cloned human prostate cancer cells representing a phenotypic
continuum of cancer progression. Nutr. Cancer (in press).
Lichtenstein, G.R., J.J. Deren, S. Katz, J.D.
Lewis, A.R. Kennedy and J.H. Ware. Bowman-Birk Inhibitor Concentrate:
a novel therapeutic agent for patients with active ulcerative
colitis. Dig. Dis. Sci. 53(1): 175-180, 2008.
Stewart, J., Ko, Y-H. and Kennedy, A.R. Mechanisms
by which L-selenomethionine protects against space radiation
biological effects. Radiation & Environmental Biophysics
46 (2): 161-5, 2007.
Search PubMed for more articles
Lab
Rotation Projects
A study on the role of OXR1 in mechanisms underlying the
cancer preventive role of SeM. In a search for human genes
that function in protection against oxidative damage, an oxidation
resistance gene, OXR1, has been discovered by Volker et. al.
(PNAS, 2000, Vol. 97 no. 26). Using Gene Chip Microarray Technology
(Affymetrix), we have identified OXR1 as one of the genes
whose expression is regulated in prostate carcinoma (LNCaP)
cells supplemented with L-Selenomethionine (SeM). As a part
of a larger endeavor aimed at deciphering the mechanism(s)
by which SeM plays a role as a protective agent against radiation-induced
cancer, a specific project would be to examine the involvement
of OXR1 in a SeM induced cascade(s). This project would involve
use of quantitative PCR for monitoring of OXR1 transcriptional
levels in human thyroid cells (HTori-3 cells), exposed to
ionizing radiation in the presence or absence of selenomethionine
(SeM). Further, the siRNA methodology would be used to prevent
expression of OXR1 to investigate whether it is required for
SeM protection of irradiated HTOri-3 cells against oxidative
stress and transformation. Our belief is that OXR1 will be
shown to play a role in the prevention of radiation induced
DNA damage, whereby it will be a useful target in both cancer
prevention and radiation therapy.
Generation of SeM database and data analysis using bioinformatics
tools. In our efforts to explain the chemopreventive effects
of SeM, various cell types are treated with this agent and
gene expression data are collected. A specific project would
involve generation of a database for the HTori-3 cell line
(human thyroid) and its analysis for gene candidates that
could be used either as biomarkers in cancer treatment or
as targets in drug design.
- Lab Personnel:
Jeff Ware, PhD - Research Specialist D
Steven Wan, PhD - Senior Research Investigator
Zhaozong Zhou, MD - Reserach Specialist C
Jenine Sanzari, PhD - Postdoctoral fellow
Manunya Nuth, PhD - Postdoctoral Fellow
Carly Sayers - Graduate Student, Pharmacology Graduate Student
Gabriel Krigsfeld - Rotating Graduate Student, Pharmacology Graduate Group
Trisha Agrawal - Rotating Graduate Student, Pharmacology Graduate Group
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last updated 9/2008
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