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Full-Time Faculty and Researchers
* Ann E. Campbell, Ph.D.
* Richard P. Ciavarra, Ph.D.
* Dianne C. Daniel, Ph.D.
* Richard R. Drake, Ph.D.
* Aurora Esquela-Kerscher, Ph.D.
* Laura K. Hanson, Ph.D.

* Julie A. Kerry, Ph.D.
* Woong-Ki Kim, Ph.D.
* Neel K. Krishna, Ph.D.

* Patric S. J. Lundberg, Ph.D.
* O. John Semmes, Ph.D.
* Julius O. Nyalwidhe, Ph.D.
* Margaret J. Wortman, Ph.D.
* William J. Wasilenko, Ph.D.
Staff
Dept. Directory

Dept. of Microbiology and Molecular Cell Biology

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Richard R. Drake, Ph.D.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)

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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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