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Division of Clinical Chemistry


Email dchan@jhmi.edu
Phone (410) 955-2674

Daniel W. Chan, Ph.D.

Director, Division of Clinical Chemistry
Primary Appointment in Pathology; Secondary Appointments in Urology, Radiology, Oncology


The focus of my research is cancer proteomics. We identify cancer biomarkers using high throughput approaches, such as SELDI-TOF (surface-enhanced laser desorption ionization - time of flight) mass spectrometry. Once protein markers are identified, we develop antibodies and immunoassays for clinical studies. Bioinformatics is used to analyze and enhance the clinical usefulness of these biomarkers for the early detection of cancer. Studies are being conducted on patient specimens from prostate, breast, colorectal, and ovarian cancer. Our laboratory is involved in the Human Proteome Project (HUPO). This research will lead to a greater understanding of the importance of human proteome in the diagnosis and management of human cancer.

Publications
Diamandis E.P., Fritsche H.A., Lilja H., Chan D.W., Schwartz M.K., eds. Tumor Markers: Physiology, Pathobiology, Technology, and Clinical Applications. AACC Press, Washington, DC, 2002.

Clarke W., Zhang Z., Chan D.W. The application of clinical proteomics to cancer and other diseases. Clin. Chem. Lab. Med. 41:1562-1570, 2003.

Li J., White N., Zhang Z., Rosenzweig J., Mangold L.A., Partin A.W., Chan D.W. Detection of prostate cancer using serum proteomics pattern in a histologically confirmed population. J. Urol. 171:1782-1787, 2004.

Rai A.J., Chan D.W. Cancer Proteomics: Serum Diagnostics for Tumor Marker Discovery. Ann. N.Y. Acad. Sci. 1022:286-294, 2004.

Zhang Z., Bast Jr. R.C., Yu Y., Li J., Sokoll L.J., Rai A.J., Rosenzweig J.M., Cameron B., Wang Y.Y., Meng X.-Y., Berchuck A., van Haaften-Day C., Hacker N.F., de Bruijn H.W.A., van der Zee A.G.J., Jacobs I.J., Fung E.T., and Chan D.W. Three biomarkers identified from serum proteomics analysis for the detection of early stage ovarian cancer. Cancer Research 64:5882-5890, 2004.




Email wclarke@jhmi.edu
Phone (410) 502-7692

Related Websites
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William Clarke, Ph.D.

Primary Appointment in Pathology
Member, Graduate Program in Biochemistry, Cellular and Molecular Biology


My research interests primarily involve the development of analytical methods for drug analysis. This includes the development and implementation of tandem mass spectrometry and high resolution-accurate mass (HRAM) mass spectrometry method for measurement of multiple drugs in a single sample, as well as investigation of alternative matrices for drug testing. In addition, I am interested in the application of pharmacokinetic measurements, along with pharmacogenetic testing, to clinical management of patients. Active projects in our lab include pharmacokinetic monitoring of antidepressants and mood-stabilizing drugs in bariatric surgery patients, pharmacokinetic evaluation of antidepressant drugs in pregnant women with mood disorders, and qualitative screening for antiretroviral drugs and substances of abuse in various HIV Prevention Clinical Trials. We are also investigating ways to improve the robustness and throughput of LC-MS methods in the clinical laboratory by evaluation of newly developed technologies and alternative approaches to LC-MS method development.

Publications
Please visit Publications web link on left



Email mmarzin1@jhmi.edu
Phone (443) 287-7516
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Mark A. Marzinke, Ph.D.

Primary Appointment in Pathology; Secondary Appointment in Medicine; Associate Director, Clinical Pharmacology Analytical Laboratory (Division of Clinical Pharmacology)


My primary research focuses are in the development and validation of analytical methods for the assessment of phenotype-genotype and pharmacokinetic-pharmacodynamic (PK-PD) relationships. Specifically, my interests lie in the clinical application of molecular testing for targeted pharmacogenetic analysis using a variety of techniques, including high-resolution melting (HRM) curve discrimination of genetic polymorphisms, and probe-based quantitative PCR techniques to identify genetic aberrations, to direct drug treatment. Additionally, my work is focused on the quantification or qualitative identification of small molecules, including anti-retroviral agents and pain management medications in a variety of specimen sources to assess PK-PD relationships. Our group utilizes mass spectrometry in a variety of ways, including the development, bioanalytical validation and utilization of liquid chromatographic-tandem mass spectrometric (LC-MS/MS) and high-resolution accurate mass (HRAM) spectrometric methods for analyte identification and quantification. Other research interests include laboratory automation and workflow and process improvement initiatives.

Publications
Marzinke MA, Choi CH, Chen L, Shih IM, Chan DW, Zhang H. Proteomic Analysis of Temporally Stimulated Ovarian Cancer Cells for Biomarker Discovery. Mol Cell Proteomics 2013; 12(2): 356-368.

Marzinke MA, Clarke W, Wang L, Cummings V, Liu TY, Piwowar-Manning E, Breaud A, Griffith S, Buchbinder S, Shoptaw S, Del Rio C, Magnus M, Mannheimer S, Fields SD, Mayer KH, Wheeler DP, Koblin BA, Eshleman SH, Fogel JM. Nondisclosure of HIV Status in a Clinical Trial Setting: Antiretroviral Drug Screening Can Help Distinguish Between Newly Diagnosed and Previously Diagnosed HIV Infection. Clin Infect Dis. 2014 Jan;58(1):117-20. PMID: 24092804.

Seserko LA, Emory JF, Hendrix CW, Marzinke MA. The development and validation of an UHPLC-MS/MS method for the rapid quantification of the antiretroviral agent dapivirine in human plasma. Bioanalysis. 2013; 5(22):2771-83. PMID: 24256358.

Petrides AK, Clarke W, Marzinke MA. Application and utility of pharmacogenetics in the clinical laboratory. J Analyt Molecul Tech. 2014; 1(1): 15.

Marzinke MA, Breaud A, Parsons TL, Cohen MS, Piwowar-Manning E, Eshleman SH, Clarke W. The development and validation of a method using high-resolution mass spectrometry (HRMS) for the qualitative detection of antiretroviral agents in human blood. Clin Chim Acta, 2014; 433C: 157-168.




Email lsokoll@jhmi.edu
Phone (410) 955-2673
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Lori Sokoll, Ph.D.

Primary Appointment in Pathology; Secondary Appointments in Oncology and Urology


My primary research interest is the investigation of serum tumor markers for the early detection, diagnosis, staging, and monitoring of cancer. Our focus is to develop new tumor markers and to develop new applications for existing markers in order to increase their clinical utility. We are primarily studying markers for prostate cancer and breast cancer. Other research interests include immunoassay automation and intraoperative hormone measurements.

Publications
Sokoll LJ, Mangold LA, Partin AW, Epstein JI, Bruzek DJ, Dunn W, Mohr P, Wallerson G, Chan DW. cPSA as a staging tool for prostate cancer: a prospective study in 420 men. Urology 2002;60:18-23.

Wians FH, Cheli CD, Balko JA, Bruzek DJ, Chan DW, Sokoll LJ. Evaluation of the clinical performance of equimolar- and skewed-response total prostate-specific antigen assays versus complexed and free PSA assays and their ratios in discriminating between benign prostatic hyperplasia and prostate cancer. Clin Chim Acta 2002;326:81-95.

Sokoll LJ, Chan DW, Mikolajczyk SD, Rittenhouse HG, Evans CL, Linton HJ, Mangold LA, Mohr P, Bartsch G, Klocker H, Horninger W, Partin AW. Proenzyme PSA for the early detection of prostate cancer in the 2.5-4.0 ng/mL total PSA range: preliminary analysis. Urology 2003;61:274-6.

Sokoll LJ, Wians FH, Remaley AT. Rapid intraoperative immunoassay of PTH and other hormones: a new paradigm for point-of-care testing. Clin Chem 2004;50:1126-35.




Email hzhang32@jhmi.edu
Phone (410) 502-8149

Related Websites
UniPep

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Hui Zhang, Ph.D.

Primary Appointment in Pathology


Protein modification is one of the key mechanisms that governs the diverse protein structure and function, and plays a significant role in the development of many diseases such as cancer. Unfortunately, the dynamic nature of protein modification remains uncharacterized, which is one of the major bottlenecks to biochemical research.

My primary research goal is to study protein modification on the proteome scale and the effects of modification on protein function and disease progression. For the past few years, my research has been focused on developing high-throughput technologies to isolate and identify two of the most abundant protein modifications - phosphorylation and glycosylation. One technology enables capturing and identification of modified peptides using affinity chromatography. To do so, I have developed a group of antibodies reactive against a variety of protein modification sites, such as phosphorylation, nitration, acetylation, and substrates of a specific modification enzyme, etc. Among those, phospho-specific antibodies have enabled isolation of a large number of phosphorylated peptides that can be subsequently identified by tandem mass spectrometry. The second technology enables capturing glycopeptides using solid phase extraction, which has become a powerful tool to analyze glycoproteins on cell surface and in body fluids. Thus far, thousands of novel glycosylation sites have been identified from different tissues using this novel glycopeptide capture technology; this significantly expends the limited number of experimentally identified glycosylation sites prior to the new technology. These methods are highly sensitive, holding a strong promise for discovering low abundance disease marker proteins in tissue, plasma or other body fluids.

Currently, we are applying these proteomics technologies to determine protein modifications associated with cancer for early detection and monitoring therapeutic effects as well as developing novel methods to study protein modifications that will have major implications for human health.

Publications

Tian, Y., Zhou, Y., Elliott, S., Aebersold, R., and Zhang. H. Solid-phase extraction of N-linked glycopeptides. Nature Protocols (2007) 2: 334.

Zhang, H., Liu, A. Y., Loriaux, P., Wollscheid, B., Zhou, Y., Watts, J. D., and Aebersold, R. Mass spectrometric detection of tissue-derived proteins in blood. Molecular & Cellular Proteomics (2007) 6: 64.

Zhang, H., Loriaux, P., Eng, J., Campbell, D., Keller, A., Moss, P., Bonneau, R., Zhang, N., Zhou, Y., Wollscheid, B., Cooke, K., Yi, E. C, Lee, H, Peskind, E. R., Zhang, J., Smith, R. D., and Aebersold, R. UniPep, a database for human N-linked glycosites: A Resource for Biomarker Discovery. Genome Biology (2006) 7: R73.

Zhang, H., Li, X. J., Martin, D. B., and Aebersold, R. Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nature Biotechnology (2003) 21:660.

Zhang, H., Zha, X., Tan, Y., Hornbeck, P. V., Mastrangelo, A. J., Alessi, D. R., Polakiewicz, R. D., and Comb, M. J. Phosphoprotein analysis using antibodies broadly reactive against phosphorylated motifs. Journal of Biological Chemistry (2002) 277:39379.




Email zzhang7@jhmi.edu
Phone (410) 502-7871
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Zhen Zhang, Ph.D.

Primary Appointment in Pathology


My research interests are in the development and application of bioinformatics tools for clinical diagnosis. What used to be considered as a single diagnosis may actually consist of a number of different phenotypes with distinguished disease pathways and varying genomic and proteomics expression patterns. I am interested in deriving new mathematical and computational algorithms to identify such patterns for biomarker discovery and use them to establish predictive models for the diagnosis and management of diseases. Currently, our effort is focused on tumor marker discovery using high throughput proteomics approaches.

Publications
Zhang Z., Barnhill S.D., Zhang H., Xu F., Yu Y., Jacobs I., Woolas R.P., Berchuck A., Madyastha K.R., Bast R.C. Jr. Combination of multiple serum markers using an artificial neural network to improve specificity in discriminating malignant from benign pelvic masses. Gynecol Oncol. 1999; 73(1):56-61.

Li J, Zhang Z., Rosenzweig J., Wang Y., Chan D.W. Proteomics and bioinformatics approaches for identification of serum biomarkers to detect breast cancer. Clin. Chem., 2002 Aug;48(8):1296-1304.

Zhang Z. Combining Multiple Biomarkers in Clinical Diagnostics - A review of Methods and Issues. In: Diamandis E.P., Fritsche H.A., Lilja H.,Chan D.W., Schwartz M.K., eds. Tumor Markers: Physiology, Pathobiology, Technology and Clinical Applications. AACC Press, Washington, DC, 2002.

Buckhaults P., Zhang Z., Chen Y.C., Wang T.L., St Croix B., Saha S., Bardelli A., Morin P.J., Polyak K., Hruban R.H., Velculescu V.E., Shih IeM. Identifying tumor origin using a gene expression-based classification map. Cancer Res. 2003; 63(14):4144-9.

Zhang Z., Bast R.C. Jr, Yu Y., Li J., Sokoll L.J., Rai A.J., Rosenzweig J.M., Cameron B., Wang Y.Y., Meng X.Y., Berchuck A., Van Haaften-Day C., Hacker N.F., de Bruijn H.W., van der Zee A.G., Jacobs I.J., Fung E.T., Chan D.W. Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer. Cancer Res. 2004; 64(16):5882-90.



 


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