Professor
Co-Director, George L. Wright, Jr., Center for Biomedical Proteomics

Lewis Hall, #3114
Office: (757) 446-5656
Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

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 within the newly created Cancer Biology and Infectious Disease Research Center are being applied to early cancer diagnosis and prognosis research, and characterization of emerging and biodefense pathogens. 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 in the George L. Wright, Jr. Center for Biomedical Proteomics. 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., Julius O. Nyalwidhe, 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 aggressive 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 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.

Selected Publications

• 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. 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., 8, 4182-4192.
• 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
• Cazares, L.H., Troyer, D.A., Mendrinos, S., Lance, R.S., Nyalwidhe, J.O., Clements, M.A., Drake, R.R. and Semmes, O.J. (2009) Imaging Mass Spectrometry of a Specific Fragment of MEKK2 Discriminates Cancer from Uninvolved Prostate Tissue. Clin. Cancer Res., 15, 5541-5551.
• Mellmann, A., Bimet, F., Bizet, C., Borovskaya, A.D., Drake, R.R., Eigner, U., Fahr, A.M., He, Y., Ilina, E.N., Kostrzewa, M., Maier, T., Mancinelli, L., Moussaoui, W., Prévost, G., Putignani, L., Seachord, C.L., Tang, Y.W. and Harmsen, D. (2009) High interlaboratory reproducibility of matrix-assisted laser desorption ionization-time of flight mass spectrometry-based species identification of nonfermenting bacteria. J Clin Microbiol. 47, 3732-3734.
• Drake, R.R., Elschenbroich, S., Lopez-Perez, O., Kim, Y., Ignatchenko, V., Ignatchenko, A., Nyalwidhe, J.O., Basu, G., Wilkins, C.E., Gjurich, B., Lance, R.S., Semmes, O.J., Medin, J.A., and Kislinger, T. (2010) In-Depth Proteomic Analyses of Direct Expressed Prostatic Secretions. J Proteome Res., In press.