Contents 1 Faculty Appointments 2 Academic History 3 Positions and Employment 4 Honors 5 Current Graduate Students 6 Research 7 Recent Publications

Mark Chance, Ph.D.

Case Western Reserve University

Center for Proteomics

10900 Euclid Ave., BRB 930

Cleveland, OH 44106-4988

Phone: (216) 368-4406

Fax: (216) 368-6846

Email: mark.chance@case.edu

[edit] Faculty Appointments

Case Center for Proteomics (Director, Professor)

Physiology and Biophysics (Primary)

Department of Pharmacology (Secondary)

Department of Pathology (Secondary)

[edit] Academic History

1986 Ph.D., Biophysics, University of Pennsylvania

1986-1988 Post-doctoral Fellow, Biophysics, AT&T Bell Labs

[edit] Positions and Employment

1984-1998 Visiting Scientist, AT&T Bell Laboratories, Murray Hill, NJ

1988-1992 Assistant Professor in Chemistry, Georgetown University

1993-1995 Director, Biostructures PRT, Beamline X9B, National Synchrotron Light Source

1994-2005 Director, Molecular Biophysics Training Program, Albert Einstein College of Medicine

1993-1998 Associate Professor in Physiology & Biophysics and Biochemistry, Albert Einstein College of Medicine

1998-2005 Professor of Physiology & Biophysics and Biochemistry, Albert Einstein College of Medicine

1995- Director, Center for Synchrotron Biosciences, National Synchrotron Light Source, Brookhaven Labs

2005- Director, Case Center for Proteomics and Cleveland Foundation Center for Proteomics

2005- Professor of Physiology & Biophysics, Case Western Reserve Medical School, Cleveland OH

2006- CEO, NEO Proteomics, Inc. Cleveland, OH

[edit] Honors

1980 Hawk Prize in Biochemistry, Wesleyan University

1980-1984 NIH Graduate Fellow, Massachusetts Institute of Technology, Department of Biology

1985-1986 Cardiovascular Fellow, University of Pennsylvania, Department of Biochemistry and Biophysics

1990-1992 The Upjohn Company New Faculty Research Award

1995-2002 Joseph & Anne Wunsch Fellow in Biophysical Engineering, Albert Einstein College of Medicine

1996-2001 Irma T. Hirschl Career Scientist Award

2003 Dean’s Achievement Award, Albert Einstein College of Medicine

[edit] Current Graduate Students

Rod Nibbe (Pharmacology, CASE)

Vishal Patel (Unaffiliated, CASE)

[edit] Research

The research in my laboratory is focused in the important areas of structural and cellular proteomics. High throughput methods are revolutionizing structural biology through structural genomics initiatives. We are using these advances to identify the structure and function of large macromolecular complexes in areas relevant to iron transport, mis-match repair, and actin filament assembly. New technologies in mass spectrometry are also allowing protein expression, localization, and interactions to be studied in increasing detail and on a genome wide scale. Our expertise in quantitative mass spectrometry and 2-D gel technologies are being applied to identify biomarkers and regulatory pathways in colon cancer, diabetes, radiation exposure, and HIV infection.

In structural biology, structural genomics has as its goal the provision of structural models for all possible open reading frame sequences. This will be accomplished by solving the structures of 5,000-10,000 carefully selected target proteins, each one a member of a distinct protein family. The remainder of the structures will be solved by comparative modeling. Our experience in the New York Structural GenomiX Research Consortium with the 200 structures that have been solved so far is that we can model over 500 additional open reading frame sequences for each solved structure.

Although structural genomics is rapidly progressing, our progress to date clearly identifies the next biological hurdle. High-throughput structural biology is optimized to examine the structure of small soluble protein domains, while critical functions of biology are controlled by larger multi-protein complexes. The availability of high resolution domain structures is critical to understanding the assemblies, the domains must "dock" with each other in a functionally relevant fashion. The long term structural goals of my laboratory are focused on understanding the structure and dynamics of these assemblies. We are using biochemical approaches, mass spectrometry, crystallography, cryo-EM, cross-linking, footprinting, and molecular modeling to understand the physiologically relevant functional states.

In our expression proteomics studies, examining the post-translational modifications, amounts, and interactions of proteins are combined in integrated studies to understand the pathology of human disease. Working with investigators across the Case campus and across NE Ohio, we are developing new biomarkers to direct therapeutic approaches for patients, probing fundamental regulatory mechanisms of disease, and comparing these markers and regulatory mechanisms to those seen in normal development and normal physiology.

[edit] Recent Publications

• Bonanno, J.B., Almo, S.C., Bresnick, B., Chance, M.R., Fiser, A., Swaminathan, S., Jiang, J., Studier, F.W., Shapiro, L., Lima, C., Gaasterland, T.M., Sali, A., Bain, K., Feil, I., Gao, X., Lorimer, D., Ramos, A., Sauder, M., Wasserman, S., Emtage, S., D’Amico, K., Burley, S.K., “New York-Structural GenomiX Research Consortium (NYSGXRC): a large scale center for the protein structure initiative.” J. Struct. Funct. Genomics, 6:225-32 (2005).

• Marinkovic, N., Chance M.R., “Synchrotron Infrared Microscopy.” Encyclopedia of Molecular Cell Biology and Molecular Medicine, 2nd Ed., R. Meyers, Editor, Wiley Inc., Volume 13, p. 671-700 (2005).

• Shi, W., Zhan, C., Manjasetty, B., Marinkovic, N., Sullivan, M., Huang, R, and Chance, M.R., “Metalloproteomics-high throughput determination of transition metal content of metalloproteins.” Structure, 13:1473-86 (2005).

• Xu, G., Liu, R., Zak, O., and Aisen, P., and Chance, M.R., “Structural allostery and binding of the transferrin-receptor complex.” Mol Cell Proteomics. 4:1959-1967 (2005).

• Brenowitz, M., Erie, D.A., and Chance, M.R., “Catching RNA polymerase in the act of binding: intermediates in transcription illuminated by synchrotron footprinting.” Proc Natl Acad Sci USA. 2005;13: 4659-60.

• Guan, J.Q., Chance, M.R. “Structural Proteomics of Macromolecular Assemblies using Oxidative Footprinting and Mass Spectrometry.” Trends in Biochemical Sciences, 2005;10:583-92.

• Takamoto, K., Chance, M.R. “A new approach for nucleic acid footprinting data analysis.” Biotechnology Journal (Japan) 5:194-197 (2005).

• Xu, G., Chance, M.R., “Radiolytic Modification and Reactivity of Amino Acid Residues Serving as Structural Probes for Protein Footprinting.” Anal. Chem., 77:4549-55 (2005).

• Xu, G., Kiselar, J., & Chance, M.R., “Secondary Reactions and Strategies to Improve Quantitative Protein Footprinting.” Anal. Chem., 77:3029-37 (2005).

• Xu, G., Chance, M.R., “Radiolytic Modification of Sulfur Containing Acidic Amino Residues in Model peptides: Fundamental Studies for Protein Footprinting.” Anal. Chem., 77:2437-2449, 2005. (2005).

• Guan, J.Q., Takamoto, K., Almo, S.C., Reisler, E., and Chance, M.R., “Structure and dynamics of the actin filament.” Biochemistry, 44:3166-3175 (2005).

• Zhan, C., Fedorov, E.V., Shi, W., Ramagopal, U.A., Thirumuruhan, R., Manjasetty, B.A., Almo, S.C., Fiser, A., Chance, M.R., Fedorov, A.A, “The ybeY protein from E.coli is a metalloprotein containing nickel”, Acta. Cryst. , F61, 959-963, (2005).

• Takamoto, K., Chance, M.R., “Radiolytic protein footprinting with mass spectrometry to probe the structure of macromolecular complexes.” Annu. Rev. Biophys Biomol. Struct., 35:251-76 (2006).

• Zheng, Q.Y., Rozanas, C.R., Thalmann, I., Chance, M.R., and Alagramam, K.N., “Inner ear proteomics of mouse models for deafness, a discovery strategy.” Brain Res. 1091(1):113-21 (2006).

• Mukherjee, P.K., Mohamed, S., Chandra, J., Kuhn, D., Liu, S., Antar, O.S., Munyon, R., Mitchell, A.P., Andes, D., Chance, M.R., Rouabhia, M. and Ghannoum, M.A. “Alcohol dehydrogenase modulates the ability of the pathogen Candida Albicans to form biofilm on catheter surfaces through an ethanol-based mechanism.” Infection and Immunity. 74(7):3804-16 (2006).

• Shi W, et al., Chance MR Beamline X29: a novel undulator source for X-ray crystallography. J. Synchrotron Radiation, 13: 365-372 (2006).

• Manjasetty, B. A., and Chance, M. R. Crystal structure of Escherichia coli L-arabinose isomerase (ECAI), the putative target of biological tagatose production Journal of Molecular Biology 360(2), 297-309 (2006).

• Manjasetty, B.A., Shi, W. Zhan, C., Fiser, A., Chance, M.R. “A High-Throughput Approach to Protein Structure Analysis”, Genetic Engineering, Vol. 28: 105-128, (2006).

• Takamoto, K., Chance, M.R. “Biological and Chemical Implications of a Three Dimensional Model of Monomeric Actin Bound to Magnesium Chelated ATP” Structure, accepted, (2006).

• Kiselar, J., Mahaffy, R., Pollard, T.D., Almo, S.C., Chance, M.R. “Arp2/3 activation mediated by binding of nucleotides and WASp: Structural mass spectrometry approaches to large macromolecular complexes” PNAS, accepted, (2006).