Richard R. Drake, PhD
Director, MUSC Proteomics Center
SmartState Endowed Chair of Proteomics
1990 Ph.D., University of Kentucky
Office: CRI 314
MALDI Imaging Mass Spectrometry and Glycoprotein Biomarkers of Cancer
In my laboratory, we are applying a variety of mass spectrometry-based approaches to identify molecular diagnostic and prognostic biomarkers of cancer, using the resources within the MUSC Proteomics Center and Mass Spectrometry Facility. Our emphasis is on the application of these resources for imaging mass spectrometry analysis of clinically derived tissues, fluids and exosomes to develop proteomic-based or small molecule diagnostic assays, with a particular focus on glycosylation and its role in disease. A new state-of-the-art, translational MALDI Imaging Research Center has been created. The facility is anchored by a dual-source Bruker Daltonic 7T solariX FTICR mass spectrometer, as well as a new rapifleX TIssueTyper MALDI-TOF, autofleX III MALDI-TOF and an HTX TM sprayer. These are complemented by a Thermo Orbitrap Elite mass spectrometer and an Agilent Triversa Nanomate with LESA-MS for direct analysis of post-translational modifications to proteins. This instrumentation is being applied to multiple translational cancer research projects within my laboratory, as well as collaborations within the department and throughout the NCI-designated Hollings Cancer Center. These projects combine the capabilities of the MUSC Proteomics Center with clinical research, lipidomic, biorepository and molecular pathology resources, as well as strong collaborations with other Center principal investigators, Peggi Angel, Anand Mehta and Lauren Ball. Current types of cancer being targeted include prostate, breast, liver, colon, kidney, lung and pancreatic cancers. The major research areas of the Drake laboratory are summarized as follows.
MALDI Mass Spectrometry Tissue Imaging of Glycans, Lipids, Proteins and Drug Metabolites - MALDI imaging mass spectrometry (MALDI-IMS) is an established method used primarily to spatially profile proteins, lipids, drug and small molecule metabolites in tissues. Using the resources of the MUSC Proteomics Center and MALDI Imaging Research Center, our group has recently developed a glycobiology approach using on-tissue peptide N-glycanase F (PNGaseF) digestion to directly profile released N-linked glycans in their local microenvironment. This method, co-developed with another MUSC investigator, Anand Mehta, has recently been optimized for use with formalin-fixed paraffin-embedded tissues obtained directly from pathology collections. The approach is being applied to map the two-dimensional N-linked glycomes associated with prostate, breast, pancreatic, liver, kidney, colon and lung cancers. A comprehensive prostate cancer tissue glycome analysis is ongoing with multiple MUSC investigators as part of a U54 program directed by Chanita Hughes-Halbert. Several biomarker studies are ongoing with Jennifer Wu, now at Northwestern University, with a goal to identify tissue glycome biomarkers indicative of tumor immune status and the most lethal forms of prostate cancer. The approach also works well with tissue microarrays representing prostate, lung, breast and pancreatic cancers in efforts to identify glycan biomarker panels indicative of disease state. A longer term goal is to use the N-linked glycome maps to link these glycans back to their original glycoprotein carriers, which represents a second tier of biomarker targets. Recent NIH Common Fund in Glycomics support has facilitated the expansion of these glycomic approaches to develop new MALDI imaging methods to tissue profile O-glycans and glycosaminoglycans.
Another research emphasis is the development of methods to spatially profile bioactive ceramide, sphingosine and glycolipid specie distribution in tissues of clinical interest, supported in part by an NCI program project with Besim Ogretmen and other lipidomic researchers at MUSC. A reference database of ceramide and glycosphingolipid masses for use in tissue imaging analysis has been created using tissues derived from lysosomal storage disease models (in collaboration with Jeffrey Medin, Medical College of Wisconsin). Drug uptake and metabolism in tissues derived from pre-clinical model systems is also ongoing, working in conjunction with researchers in the Hollings Cancer Center and the Developmental Cancer Therapeutics program. Additionally, since 2006, my laboratory has been part of a systemic effort to characterize and identify potential biomarker targets in proximal fluids of the prostate, including direct prostatic fluids obtained just prior to prostatectomy, and expressed prostatic secretions in urine obtained in the urology clinic following digital rectal exam. Our recent publications cumulatively describe the identification of over 1100 proteins identified in post-DRE expressed prostatic secretions in urine (EPS-urine) and prostatic fluids termed direct EPS obtained at the time of prostatectomy. Lastly, we have completed the proteome analysis of exosomes from pooled EPS samples from benign, indolent and aggressive cancers. These studies are continuing via an ongoing collaboration with an innovative exosome isolation company, Ymir Genomics, to further evaluate the lipid, protein and glycan components of prostate cancer associated urine exosomes. Other collaborative efforts at MUSC are ongoing to apply this approach to clinical urine exosomes from donors with lupus nephritis, other kidney diseases and bladder cancer.
Recent Publications | Additional Publications
1. Drake, R.R., Powers, T.W., Jones, E.E., Bruner, E., Angel, P. (2017) MALDI mass spectrometry imaging of N-linked glycans in cancer tissues. Adv Cancer Res.,134, 85-116.
2. Barnett, D., Liu, Y., Partyka, K., Huang, Y., Tang, H., Hostetter, G., Brand, R.E., Singhi, A.D., Drake, R.R., Haab, B.B. (2017) The CA19-9 and Sialyl-TRA Antigens Define Separate Subpopulations of Pancreatic Cancer Cells. Sci Rep, 7(1), 4020.
3. Neely, B.A., Wilkins, C.E., Marlow, L.A., Malyarenko, D., Kim, Y., Ignatchenko, A., Sasinowska, H., Sasinowski, M., Nyalwidhe, J.O., Kislinger, T., Copland, J.A., and Drake, R.R. (2016) Proteotranscriptomic Analysis Reveals Stage Specific Changes in the Molecular Landscape of Clear-Cell Renal Cell Carcinoma. PLoS One. 11, e0154074.
4. Kim, Y., Jeon, J., Mejia, S., Yao, C.Q., Ignatchenko, V., Nyalwidhe, J.O., Gramolini, A.O., Lance, R.S, Troyer, D.A., Drake, R.R., Boutros, P.C., Semmes, O.J., and Kislinger T. (2016) Targeted proteomics identifies liquid-biopsy signatures for extracapsular prostate cancer. Nature Comm, 7,11906.
5. Heijs, B., Holst, S., Briaire-de Bruijn, I.H., van Pelt, G.W., de Ru, A.H., van Veelen, P.A., Drake, R.R., Mehta, A.S., Mesker, W.E., Tollenaar, R.A., Bovée, J.V., Wuhrer, M., and McDonnell, L.A. (2016) Multimodal Mass Spectrometry Imaging of N-Glycans and Proteins from the Same Tissue Section. Anal Chem., 88, 7745-7753.
6. Holst, S., Heijs, B., de Haan, N., van Zeijl, R.J., Briaire-de Bruijn, I.H., van Pelt, G.W., Mehta, A.S., Angel, P.M., Mesker, W.E., Tollenaar, R.A., Drake, R.R., Bovee, J.V., McDonnell, L.A.,,and Wuhrer, M. (2016) Linkage-specific in-situ sialic acid derivatization for N-glycan mass spectrometry imaging of FFPE tissues. Anal Chem, 88, 5904-5913.
7. Reatini, B.S., Ensink, E., Liau, B., Sinha, J.Y., Powers, T.W., Partyka, K., Bern, M., Brand, R.E., Rudd, P.M., Kletter, D., Drake, R., Haab, B.B. (2016) Characterizing Protein Glycosylation through On-Chip Glycan Modification and Probing. Anal Chem, 88, 11584-11592.
8. Drake R.R., Jones, E.E., Powers, T.W., and Nyalwidhe, J.O. (2015) Altered glycosylation in prostate cancer. Adv Cancer Res., 126, 345-382.
9. Powers, T.W., Neely, B.A., Shao, Y., Tang, H., Troyer, D.A., Mehta, A.S., Haab, B.B., and Drake, R.R. (2014) MALDI Imaging Mass Spectrometry Profiling of N-Glycans in Formalin-Fixed Paraffin Embedded Clinical Tissue Blocks and Tissue Microarrays. PLoS One, 9, e106255.
10. Jones, E.E., Dworski, S., Canals, D., Casas, J., Fabrias, G., Schoenling, D., Levade, T., Denlinger, C., Hannun, Y.A., Medin, J.A., and Drake, R.R. (2014) On-Tissue Localization of Ceramides and other Sphingolipids by MALDI Mass Spectrometry Imaging. Anal. Chem., 86, 8303-8311.
11. Drake, R.R. and Kislinger, T. (2014) The Proteomics of Prostate Cancer Exosomes. Expert Rev. Proteomics, 11, 167-177.
12. Powers, T.W., Jones, E.E., Betesh, L.R., Romano, P., Gao, P., Copland, J.A., Mehta, A.S., Drake, R.R. (2013) A MALDI Imaging Mass Spectrometry Workflow for Spatial Profiling Analysis of N-linked Glycan Expression in Tissues. Anal. Chem., 85, 9799-9806.
13. Roper, S.M., Zemskova, M., Neely, B.A., Martin, A., Gao, P., Jones, E.E., Kraft, A.S., Drake R.R. (2013) Targeted Glycoprotein Enrichment and Identification in Stromal Cell Secretomes using Azido Sugar Metabolic Labeling. Proteomics Clin App., 7, 367-371.
14. Drake R.R., Boggs, S.R., Drake, S.K. (2011) Pathogen identification using mass spectrometry in the clinical microbiology laboratory. J Mass Spectrom., 46, 1223-1232.