 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 rapid and continued
development 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, a variety of 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 emerging and
biodefense pathogen infections and vaccine research. Our
emphasis is the application of these tools for analysis of
clinically derived samples to develop proteomic-based
diagnostic assays. Multiple MALDI-TOF (matrix-assisted laser
desorption ion time-of-flight) mass spectrometers with LC-MALDI
and Tissue Imaging workstations, two tandem LC-MS/MS
instruments and a hybrid triple quadropole MS/MS instrument
are utilized. The main project areas are summarized as
follows:
Cancer Proteomic,
Glycomic and MS-Imaging projects: Our primary cancer
being targeted is prostate cancer, with an additional
emphasis on kidney and breast cancers. A biorepository of
over 30,000 specimens, including tissues (frozen and
paraffin-embedded), plasma, serum, urine, seminal plasma and
expressed prostatic secretions (EPS) provides the bulk of
our prostate cancer resources. In collaboration with Drs. O.
John Semmes, Ph.D., Dean Troyer, M.D. and Raymond Lance,
M.D., 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. This is part of
our large scale effort to characterize the secreted, largely
glycosylated protein constituents of EPS urines and pure
prostatic fluids. We have also initiated studies on
characterizing the glycoconjugate components of these
proteins. Specifically, characterization of the glycan
structures on prostate specific antigen and prostatic acid
phosphatase isolated from prostatic fluids reflective of
prostatic disease state is a primary focus. 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.
Other translational efforts focus on the standardization of
collection and sample stability/storage issues for these
expressed prostatic fluid samples. In collaboration with the
NCI Early Detection Research Network, we continue to perform
protein profiling analyses of serum from healthy control
patients compared with serum from patients with breast,
esophageal, liver and colon cancers.
A new research focal area
is the use of MALDI-TOF mass spectrometry imaging of
prostate cancer and renal carcinoma tissue samples. For
prostate cancer, the emphasis is on identifying tissue
biomarkers of early cancer and micrometastatic disease. For
renal cancers, the emphasis is on characterizing protein
biomarkers of micrometastases and disease recurrence. These
studies take advantage of our large clinical biorepository
of urological specimens in the Virginia Prostate Center and
collaborators at the Mayo Clinic Jacksonville. The goal will
be to develop pathology driven imaging assays to assist
pathologists and clinicians in identifying early cancer
occurrence and early signatures of micrometastatic disease.
Biodefense and
Emerging Infectious Disease 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. In collaboration with Dr. Stephen
Buescher, M.D., director of the Clinical Microbiology
laboratory at the Children’s Hospital of the Kings Daughters
(CHKD), and collaborators at Bruker Daltonics, we are
applying the Bruker MALDI BioTyper microorganism
identification database to clinical samples obtained at
CHKD. An emphasis is being placed on identifying
microorganisms that are not readily identifiable by routine
clinical practice, particularly in immunocompromised
patients. An additional emphasis is on being placed on
characterizing different strains of hospital and community
acquired methicillin-resistant S. aureus (MRSA) strains.
Related proteomic analyses of MRSA strains and their
interaction with specific host immune proteins is ongoing
with Dr. Kenji Cunnion, M.D., Department of Pediatrics, CHKD
and EVMS. Other active collaborations are ongoing for
development of other viral diagnostic assays with the
Southwest Foundation for Biomedical Research in San Antonio,
Texas, 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.
- 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.
- 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.
- 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. J. Am. Coll. Surg, 204,1065-1071.
- Drake, R.R., Cazares, L.H.
and Semmes, O.J. (2007) Mining the Low Molecular Weight
Proteome of Blood. Proteomics, Clinical Applications, 1,
758-768.
- Tracy, M.B., Chen, H.,
Weaver, D., Malyarenko, D.I., Sasinowski, M., Cazares, L.H.,
Drake, R.R., Semmes, O.J., Tracy, E.R. and Cooke, W.E.
(2008) Precision Enhancement of MALDI-TOF-MS Using High
Resolution Peak Detection and Label-Free Alignment.
Proteomics, 8:1530-1538.
- Drake, R.R., White, K.Y.,
Fuller, T.W., Igew, E., Clements, M.A., Nyalwidhe, J.O.,
Given, R.W., Lance, R.A., and Semmes, O.J. (2009) Clinical
Collection and Protein Properties of Expressed Prostatic
Secretions as a Source for Biomarkers of Prostatic Disease.
J. of Proteomics, In Press.
- White, K.Y., Rodemich,
L.,Nyalwidhe, J.O., Comunale, M.A., Clements, M.A., Lance,
R.S., Schellhammer, P.F., Mehta, A., Semmes, O.J., and
Drake, R.R. (2009) Glycomic Characterization of Prostate
Specific Antigen and Prostatic Acid Phosphatase in Prostate
Cancer and Benign Disease Seminal Plasma Fluids. J. of
Proteome Res., In press.
- Karbassi, I.D., Cazares,
L.H, Lance, R.S., Semmes, O.J and Drake, R.R. (2009)
Proteomic Expression Profiling and Identification of Serum
Proteins Using Immobilized Trypsin Beads with MALDI-TOF/TOF.
J. of Proteome Res., In press.
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