 O.
John Semmes, Ph.D.
Anthem Professor for Cancer
Research
Professor, Department of Microbiology and Molecular Cell
Biology
Professor, Department of Pathology and Anatomy
Scientific Director, Virginia Prostate Center
Director, George L. Wright, Jr., Center for
Biomedical Proteomics
Lewis Hall, #3110
Office: (757) 446-5904
Fax: (757) 446-5766
Email: semmesoj@evms.edu
Teaching: Virology,
Tumor Biology
Biomedical Sciences
Program Track:
Molecular Integrative
Biosciences (MIB)
Education
-
B.S., Auburn University
-
M.S., University of West
Florida
-
Ph.D. George Washington
University
-
Postdoctoral Training:
-
National Institute of
Allergy and Infectious Disease (NIAID) of the
National Institutes of Health (NIH)
-
Johns Hopkins
University
Research Interests
Cancer Biomarkers
Dr. Semmes directs a
multi-disciplinary team of investigators with the long-term
goal of the development and application of clinical
proteomics techniques to the early detection of cancer. This
program brings together a unique group of individuals with
the experience and expertise needed to achieve the
objectives of biomarker discovery within existing national
and international collaborative efforts, most notably the
National Cancer Institute’s Early Detection Research
Network.
The basic science expertise
of the group is in molecular biology, protein chemistry and
cancer biology, as well as experimental applied mathematics,
physical chemistry and mass spectroscopy. The clinical
expertise of the group resides in urological oncology,
ob-gyn oncology, and molecular pathology. This team of
investigators forms the basis for Dr. Semmes’ successful
translational research program. In addition, the group
includes biocomputational mathematicians, biostatisticians
and programmers to design and evaluate studies, as well as
develop methodologies to facilitate data processing in the
emerging field of clinical proteomics. These are faculty
members at either EVMS or at our neighboring institutions,
Old Dominion University and the College of William and Mary.
These research activities
benefit from the combined facilities provided by three
specialized centers of excellence: The
Virginia Prostate Center, of
which Dr. Semmes is the scientific director, houses and
supports the VPC Clinical Biorepository and the George L.
Wright Center for Biomedical Proteomics. The biorepository
has been in operation since 1990 and houses tissue and body
fluids from patients admitted to the EVMS-associated
clinical practices. Dr. Semmes established the Center for
Biomedical Proteomics in 2002 to meet the growing demands
for state-of-the-art proteomics in translational research;
the facility was recognized by EVMS and named in honor of
George L. Wright in 2005.
The Applied Research Center
of the Thomas Jefferson Laboratories houses the William and
Mary Research Institute activities and provides
state-of-the-art laser, materials and chemical physics
facilities, and the Applied Mathematics program at William
and Mary provides computational expertise in
high-dimensional data analysis and associated networking
support. Each of these specialized facilities contributes
significantly toward an outstanding research environment.
Cancers Arising from
Infectious Agents
Infection with Human T-cell
leukemia Virus (HTLV-1) leads to development of a
particularly aggressive T-cell lymphoproliferative disease,
Adult T-cell leukemia (ATL). HTLV-1 is the only known
transforming human retrovirus. However, unlike the case with
other known transforming retroviruses, ATL does not arise
from viral introduction of a cellular oncogene or
insertional activation of an endogenous proto-oncogene. The
objective of our studies is to understand the mechanisms by
which HTLV-1 causes ATL. We are particularly focusing on the
viral transactivator Tax, a 40kD protein required for
efficient transcription of the viral genome, and for
activating and repressing a variety of cellular genes
involved in control of cell growth.
Selected Publications
- Durkin SS, Guo X, Fryrear
KA, Mihaylova VT, Gupta SK, Belgnaoui SM, Haoudi A, Kupfer
GM and Semmes OJ. (2008) HTLV-1 Tax Oncoprotein Subverts the
Cellular DNA Damage Response via Binding to DNA-PK. Journal
of Biological Chemistry 283(52):36311.
- Ramadan E, Ward MD, Guo X,
Durkin SS, Sawyer A, Vilela M, Osgood C, Pothen A and Semmes OJ.
(2008) Physical and in silico Approaches Identify DNA-PK
in a Tax DNA-damage Response Interactome. Retrovirology
5:92.
- Dale McLerran, William E.
Grizzle, Ziding Feng, Ian M. Thompson, William L. Bigbee,
Lisa H. Cazares, Daniel W. Chan, Jackie Dahlgren, Jose Diaz,
Jacob Kagan, Daniel Lin, Gunjan Malik, Denise Oelschlager,
Alan Partin, Timothy Randolph, Lori Sokoll, Shiv Srivastava,
Sudhir Srivastava, Mark Thornquist, Dean Troyer, Yutaka
Yasui, Zhen Zhang, Liu Zhu and O. John Semmes. (2008)
SELDI-TOF-MS Serum Proteomic Profiling Does Not Reliably
Detect Prostate Cancer. Clinical Chemistry 54(1): 53-60.
- Dale McLerran, William E.
Grizzle, Ziding Feng, William L. Bigbee, Lionel L. Banez,
Lisa H. Cazares, Daniel W. Chan, Jose Diaz, Elzbieta Izbicka,
Jacob Kagan, Gunjan Malik, Denise Oelschlager, Alan Partin,
Timothy Randolph, Nicole Rosenzweig, Shiv Srivastava, Sudhir
Srivastava, Ian M. Thompson, Mark Thornquist, Dean Troyer,
Yutaka Yasui, Zhen Zhang, Liu Zhu, and O. John Semmes.
(2008) Analytical Validation of Protein Expression Profiling
for Diagnosis of PCa; Sources of Sample Bias. Clinical
Chemistry 54(1): 44-52.
- Gupta S, Guo X, Durkin SS,
Fryrear KF, Ward MD and Semmes OJ. (2007) HTLV-1 Tax
Oncoprotein Prevents DNA Damage-Induced Chromatin Egress of
Hyperphosphorylated huChk2. Journal of Biological Chemistry
282(40): 29431-29440.
- Gatlin-Bunai CL, Cazares
L, Cooke WE, Semmes OJ and Malyarenko DI. (2007)
Optimization of MALDI-TOF MS detection for enhanced
sensitivity of affinity-captured proteins spanning a 100 kDa
mass range. Journal of Proteome Research 6:4517-4524.
- Durkin SS, Ward MD,
Fryrear KA, Semmes OJ. (2006) Site-specific phosphorylation
differentiates active from inactive forms of the HTLV-1 tax
oncoprotein. Journal of Biological Chemistry
281(42):31705-31712.
- Drake RR, Schwegler EE,
Malik G, Diaz JI, Block T, Mehta A and Semmes OJ. (2006)
Lectin Capture Strategies Combined with Mass Spectrometry
for the Discovery of Serum Glycoprotein Biomarkers.
Molecular and Cellular Proteomics 5(10):1957-1967.
- Semmes OJ. (2006) Adult
T-cell Leukemia: a tale of two cells. Journal of Clinical
Investigation. 116:858-860.
- Xie L, Yamamato B, Haoudi
A, Semmes OJ and Green PL. (2006) The PDZ Binding Motif of
HTLV-1 Tax Promotes Virus Mediated T-cell Proliferation In
Vitro and Persistence In Vivo. Blood 107(5): 1980-1988.
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