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Thomas P. Quinn

Professor of Biochemistry
Director, Structural Biology Core

Email:	quinnt@missouri.edu
Phone:	(573) 882-6099
Lab:	(573) 882-4956
Fax:	(573) 882-5635
Office:	234A Schweitzer Hall
Mailing Address:	Biochemistry 117 Schweitzer Hall University of Missouri-Columbia Columbia, MO 65211
Research Areas:	Cancer diagnostics, radiopharmaceutical imaging and therapy; cell and molecular imaging.

Educational Background

BS		University of Miami	Miami, Fla.	Biochemistry
PhD		St. Louis University	St. Louis, Mo.	Molecular Virology

Notable Honors and Service

Director, Structural Biology Core
Gamma Sigma Delta teaching award
University of Missouri Entrepreneur of the Year (2007)

Research Description

We have established a research program to develop radiolabeled peptides and proteins as tumor specific diagnostic and therapeutic agents. Combinatorial peptide and antibody fragment libraries are being employed to identify molecules that preferentially bind tumor antigens. The tumor-avid peptides and antibody fragments are subsequently engineered to bind the medically important radionuclides into their structures. Finally, the radiolabeled peptides and proteins are investigated for their abilities to target tumor cells in vitro and in vivo.

Radiolabeled α-MSH Peptide Analogs: The goal of this project is to design radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs for melanoma imaging and therapy. α-MSH is a small tridecapeptide hormone that is involved in control of skin coloration. α-MSH receptors have been identified on human and mouse melanoma cells making them attractive targets for the development of new peptide imaging and/or therapeutic radiopharmaceuticals. We have developed an α-MSH analog (CCMSH) that is cyclized via site-specific Tc-99m, Re, or Re-188 metal coordination. The metal-cyclized CCMSH analog is radiochemically stable and retains α-MSH receptor affinity and specificity. In vivo, the Tc-99m-CCMSH complex was effective in imaging melanoma in both murine and human melanoma mouse tumor model systems. The Tc-99m-CCMSH complex exhibited high tumor uptake and retention values coupled with rapid whole body clearance kinetics. Similar biodistribution results were obtained for the Re-188-CCMSH complex in tumor bearing mice. We are currently evaluating the melanoma therapeutic efficacy of the Re-188-CCMSH and Pb-212-DOTA-ReCCMSH in vivo.

Tumor Binding Peptides Selected from Bacteriophage Display Libraries: A combinatorial approach is being used to search for small polypeptides that bind the cancer associated Thomsen-Friedenreich (T) glycoantigen and ErbB-2 receptor with high affinities and specificities. Random peptide bacteriophage display libraries were screened for molecules that bound T-antigen and ErbB-2. Two T-antigen binding peptide sequences, P30 and P10, have been shown to bind free T-antigen in solution, T-antigen displaying proteins, and breast carcinoma cells displaying T antigen on their surfaces. The P30 peptide has be shown to inhibit T-antigen mediated tumor cell adhesion between malignant melanoma cells and adhesion between tumor cells and endothelial cells. Bacteriophage libraries have also been employed to identify peptide sequences that bind the ErbB-2 receptor. The ErbB-2 receptor is upregulated in a number of cancers, including breast and prostate. A six amino acid peptide, p6.1, has been identified that binds the extracellular domain of ErbB-2. The p6.1 peptide is capable of distinguishing between tumor cells and normal cells. We are continuing to explore the molecular recognition properties and the biological activities of the T antigen and ErbB-2 binding peptides.

Selected Publications

Karasseva, N.G., Glinsky, V.V., Chen, N.X., Komatireddy, R. and Quinn, T.P. (2002) Identification and Characterization of Peptides that Bind Human ErbB-2 Selected from a Bacteriophage Display Library. J. Prot. Chem. 21, 287-296.

Glinsky, V.V., Glinsky, G.V., Glinsky, O.V., Huxley, V.H., Turk, J.R., Mossine, V.V., Deutscher, S.L., Pienta, K.J. and Quinn, T.P. (2003) Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium. Canc. Res. 63, 3805-3811.

Miao, Y., Owen, N.K., Darrell, R., Fisher, D.R., Hoffman, T.J. and Quinn, T.P. (2005) Therapeutic efficacy of a 188Re-labeled alpha-melanocyte-stimulating hormone peptide analog in murine and human melanoma-bearing mouse models. J. Nucl. Med. 46, 121-129.

Miao, Y., Hylarides, M., Fisher, D.R., Shelton, T., Moore, H., Wester, D.W., Fritzberg, A.R., Winkelmann, C.T., Hoffman, T.J. and Quinn, T.P. (2005) Melanoma Therapy via Peptide-Targeted Alpha-Radiation. Clinical Cancer Res. 11, 5616-5621.

Miao, Y, Fisher, D.R. and Quinn, T.P. (2006) Reducing the renal uptake of ⁹⁰Y and ¹⁷⁷Lu-labeled alpha-melanocyte stimulating hormone peptide analogues. Nucl Med Biol 33, 723-733.

Miao, Y., Shelton, T., and Quinn, T.P. (2007) Therapeutic Efficacy of a ¹⁷⁷Lu Labeled DOTA Conjugated Alpha-Melanocyte Stimulating Hormone Peptide in a Murine Melanoma-bearing Mouse Model. Cancer Biotherapy and Radiopharm 22:333-341.

Employment Opportunities

Post-Doctoral Opportunities

Electronic submission is encouraged, e-mail to biochemsearch@missouri.edu

Applicants should send CV and names of two references to:
Dr. Thomas Quinn
Postdoctoral Application
Biochemistry
117 Schweitzer Hall
University of Missouri-Columbia
Columbia, MO 65211

Cancer diagnostics, radiopharmaceutical imaging and therapy; cell and molecular imaging.