 Richard
R. Drake, Ph.D.
Professor
Co-Director, George L. Wright, Jr., Center for Biomedical
Proteomics
Lewis Hall, #3114
Office: (757) 446-5656
Email: drakerr@evms.edu
Teaching: Medical Microbiology and Immunology (MMI),
Medical Molecular Cell Biology (MMCB)
Biomedical Sciences Program
Track:
Molecular Integrative
Biosciences (MIB)
Education
-
B.S., Centre College,
Danville, KY
-
Ph.D., University of
Kentucky, Lexington, KY
-
Postdoctoral Training,
University of Texas Health Science Center at San Antonio
Research
The evolution of mass
spectrometry tools for evaluating proteins, combined with
the availability of the human genome sequence and other
genomic databases, has allowed unprecedented possibilities
for characterizing the proteomes of humans and pathogens in
the “post-genomic” era.
In my laboratory, different
proteomic mass spectrometry tools in the George L. Wright,
Jr. Center for Biomedical Proteomics are being applied to
early cancer diagnosis and prognosis research, and
characterization of biodefense pathogen infections and
vaccine research. Multiple MALDI-TOF (matrix-assisted laser
desorption ion time-of-flight) mass spectrometers and a
tandem LC-MS/MS are utilized. Our research emphasis is to
use these rapidly evolving proteomic tools to identify
disease-specific biomarkers and develop improved diagnostic
assays. The main project areas are summarized as follows:
Cancer proteomic and
glycomic projects: Our primary cancers being
targeted are breast and
prostate cancers, with an additional emphasis on renal,
esophageal and head/neck cancers. A biorepository of over
30,000 specimens, including tissues (frozen and
paraffin-embedded), plasma, serum, urine, and seminal
plasma. provides the bulk of our prostate cancer resources.
In collaboration with Dr. O. John Semmes, we are focusing on
developing specific glycoprotein capture strategies using
different lectin-based methodologies to identify unique
biomarkers in the many tissue and fluid samples available to
us.
A dual strategy is currently
employed. First, the lectin-captured glycoproteins from
tissue and clinical fluids are sequenced by tandem mass
spectrometry following gel electrophoresis. We have also
initiated different targeted and global profiling analysis
of the N-linked oligosaccharides on these proteins. The
second strategy is to use lectins to fractionate the complex
proteomes of the clinical samples prior to high-throughput
expression profiling studies on the MALDI-TOF instruments,
and quantitative determinations using iTRAQ labeling prior
to LC-MS/MS. In collaboration with the NCI Early Detection
Research Network, we have initiated protein profiling
analyses of serum from normal patients compared with serum
from patients with breast, esophageal, liver and colon
cancers.
My laboratory also works
closely with Roger Perry, M.D. and Christine Laronga, M.D.,
breast cancer surgeons, and Trad Wadsworth, M.D., a
head-neck cancer surgeon, on translational biomarker
discovery and profiling studies in their respective
diseases. New MALDI-MS imaging approaches and laser capture
microscopy studies are also being applied to the available
tissues. All of the data from these studies are being used
to develop novel proteomic software analysis packages, in
collaboration with researchers at the College of William and
Mary and INCOGEN, Inc., Williamsburg, VA.
Biodefense, Infectious
Disease and Influenza Vaccine projects: The
proteomic differences that occur in the pathogen infection
process can be monitored via protein display methods
(2D-gels, MALDI-MS, SELDI-MS) that allow direct comparisons
of strain variability, severity of infection, environmental
influences and the effects of genetic manipulation.
Comprehensive analysis of the proteomic changes associated
with Class A-C pathogen infection is necessary to develop
new therapeutic targets to meet the threat of these
pathogens from natural or bioterrorist exposures. Working
closely with clinicians and other research scientists in the
Scientific Center for Biodefense at EVMS, we are pursuing
the following studies:
Biomarkers of Influenza
Vaccine Efficacy in the Elderly.
Containing natural influenza infections still remains a
daunting challenge, and the looming avian influenza pandemic
requires the development of new high-throughput diagnostic
methods and novel vaccine strategies. In collaboration with
Stefan Gravenstein, M.D., and Yuping Deng, Ph.D., from the
Glennan Center for Geriatrics and Gerontology, a
longitudinal series of serum samples obtained from a cohort
of young and elderly patients, before and after trivalent
split virus influenza vaccination, has been generated. We
are using MALDI-TOF expression profiling strategies to
identify surrogate markers reflective of the immune
response. Concurrent T-cell activation and hemagglutination
inhibition serologic assays have been done to correlate
cellular and humoral responses to influenza vaccination with
protein profiling changes.
Protein profiles will be
evaluated using multiple classification algorithms, and
potential biomarker proteins will be identified by
sequencing with either a MALDI-TOF/TOF or electrospray
ion-trap tandem mass spectrometer. Comprehensive proteomic
analysis of the T-cell subsets isolated from these subjects
is also ongoing. Future studies will examine the effects of
intranasal FluMist vaccinations. Active collaborations are
also ongoing for development of other infectious disease
diagnostic assays with the Southwest Foundation for
Biomedical Research in San Antonio, TX, and with INCOGEN,
Inc., Williamsburg, VA.
Selected Publications
- Comunale, M.A., Mattu, T.S.,
Lowman, M.A., Evans, A.A., London, W.T., Semmes, O.J., Ward,
M., Drake, R., Romano, P.R., Steel, L.F., Block, T.M. and
Mehta, A. (2004) Comparative proteomic analysis of de-N-glycosylated
serum from hepatitis B carriers reveals polypeptides that
correlate with disease status. Proteomics, 4, 826-838.
- Schwegler, E.E., Cazares,
L., Steel, L.F., Adam, B., Johnson, D.A., Semmes, O.J.,
Block, T.M., Marrero, J.M. and Drake, R.R. (2005) SELDI-TOF-MS
Profiling of Serum for Detection of the Progression of
Chronic Hepatitis C to Hepatocellular Carcinoma. Hepatology,
41, 634-642.
- Drake, R.R., Cazares, L.H.,
Semmes, O.J. and Wadsworth, J.T. (2005) Serum, Salivary and
Tissue Proteomics for Discovery of Biomarkers for Head and
Neck Cancers. Exp. Rev. Mol. Diagn., 5, 93-100.
- Drake, R.R., Deng, Y.,
Schwegler, E.E. and Gravenstein, S.K. (2005) Proteomics for
Biodefense Applications: Progress and Opportunities. Exp.
Rev. Proteomics, 2, 203-213.
- Britten, R.A., Hardy, C.,
Vlahou, A., Gregory, B., Giri, P.S. and Drake, R. (2005)
Identification of Reproducible Low Mass SELDI Protein
Profiles Specific to Cisplatin Resistance in Human Ovarian
Cancer Cells. Oncology Rep., 14, 1323-1330.
- Xiong, Y., Bernardi, D.,
Bratton, S., Ward, M.D., Battaglia, E., Finel, M., Drake, R.R. and Radominska-Pandya, A. (2006) Phenylalanine 90 and 93
Are Localized within the Phenol Binding Site of Human
UDP-Glucuronosyltransferase 1A10 as Determined by
Photoaffinity Mass Spectrometry, and Site-Directed
Mutagenesis. Biochemistry, 45, 2322-2332.
- Malyarenko, D.I., Cooke,
W.E., Tracy, E.R., Drake, R.R., Shin, S., Semmes, O.J.,
Sasinowski, M., and Manos, D.M. (2006) Resampling and
deconvolution of linear time-of-flight records for enhanced
protein profiling. Rapid Commun Mass Spectrom. 20,
1670-1678.
- Drake, R.R., Schwegler,
E.E. Malik, G., Diaz, J., Block, T.M., Mehta, A. and Semmes,
O.J. (2006) Lectin Capture Strategies Combined with Mass
Spectrometry for the Discovery of Serum Glycoprotein
Biomarkers. Mol. Cell Proteomics, 5, 1957-1967.
- Shin, S., Cazares, L.H.,
Schneider, H. Mitchell, S., Semmes, O.J., Laronga, C.,
Perry, R.R. and Drake, R.R. (2007) Serum Biomarkers to
Differentiate Benign and Malignant Mammographic (BIRADS 4)
Lesions. JACS, in press.
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