Olivera J. Finn, Ph.D.

Research Interests     The projects pursued in this laboratory center on the topics of T cell mediated tumor immunity and signal transduction pathways in effector T cells. Tumor specific T cell lines and clones are derived from patients with breast and pancreatic malignancies and used as reagents to help identify tumor specific antigens. This has already led to the identification of a mucin molecule MUC1, expressed by these tumors in an altered glycosylation form capable of stimulating T cell immunity. The knowledge of the tumor associated epitope provides the basis for the generation of synthetic and recombinant tumor vaccines, currently tested in the laboratory and in the clinic. To complement the in vitro studies with human cells, we have recently added several MUC1 and HLA transgenic mouse models. A related effort in the laboratory is directed towards discovery of new tumor antigens. We are using biochemical purification of tumor-derived peptides and proteins and human dendritic cells to prime naive T cells. These T cells in turn serve to functionally identify new tumor antigens. In the last year we have isolated several tumor peptides and proteins that are good candidates for tumor specific antigens. Effector T cells which we study in tumors respond to antigen stimulation by activating several intracellular signaling pathways. We are escpecially interested in the PKC pathway as a means of promoting and controlling T cell activation and positive and negative selection during T cell development. We have generated several strains of PKC transgenic mice to explore some of these questions. A most interesting development in this area of our research is that trangenic mice that are not capable of negative selection and are immunocomromized from birth, develop many different tumors. We believe that they will be a good model to study immune surveillance, a concept that has not been experimentally explored for the lack of appropriate models.     Selected Publications     Turner MS, Cohen, PA, Finn OJ. Lack of effective MUC1 tumor antigen specific immunity in MUC1 transgenic mice results from a T helper/T regulatory cell imbalance that can be corrected by adoptive transfer of wild type Th cells. J Immunol 178(5): 2787-2793. 2007. Carlos C, Dong HF, Howard OM, Oppenheim J, Hanisch F, Finn OJ. Human tumor antigen MUC1 is chemotactic for Immature dendritic cells and elicits maturation but does not promote Th1 type immunity. J Immunol 175 (3):1628-35. 2005. Alajez NM, Schmielau J, Alter MD, Cascio M, Finn OJ. Therapeutic potential of a tumor-specific, MHC-unrestricted T-cell receptor expressed on effector cells of the innate and adaptive immune system through bone marrow transduction and immune reconstitution. Blood 105(12): 4583-9. 2005. Ramanathan RK, Lee KM, McKolanis JM, Hiltbold E, Schraut W, Moser AJ, Warnick E, Whiteside T, Osborne J, Kim H, Day R, Troetschel M, Finn OJ Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer. Cancer Immunol Immunother 54, (3): 254-264. 2005. Vlad A, Muller S, Cudic M, Paulsen H, Laszlo O Jr, Hanisch FG, Finn OJ. Complex carbohydrates are not removed during processing of glycoproteins by dendritic cells: processing of tumor antigen MUC1 glycopeptides for presentation to MHC-Class II restricted T cells. J Exp Med 11:1435-1446. 2002. Kao H, Marto JA, Hoffman TK, Shabanowitz J, Finkelstein SD, Whiteside TL, Hunt DF, Finn OJ. Identification of cyclin B1 as a shared human epithelial tumor-assciated antigen recognized by T cells. J Exp Med 194(9):1313-1323. 2001. Complete Publication Listing     Other Links     University of Pittsburgh

Office:  E1044 BST     Lab: E1001, E1002, E1018 BST     Phone: 412.648.9816     Fax:412.648.7042     ojfinn@pitt.edu     Academic Affiliations     Professor and Chair, Department of Immunology, University of Pittsburgh School of Medicine Professor, Department of Surgery, University of Pittsburgh School of Medicine Program Leader, University of Pittsburgh Cancer Institute Immunology Program     Education     Ph.D. - Stanford University (1980) Postdoc - Stanford University (1980-1982)     Grant Support     Title: T-cell immunity to epithelial tumor mucins. Agency: NIH Role: P.I. Funding Period: 1991-2008 Title: Dendritic cells - Biology and therapy - Core A Agency: NIH Role: Project Director/Core Leader Funding Period: 2004-2009 Title: Dendritic cells - Biology and therapy - Project 2 Agency: NIH Role: Project Director/Project 2 Leader Funding Period: 2004-2009 Title: SPORE in Lung Cancer Agency: NIH Role: Project Leader, Project 2: Cyclin B1 Immunotherapy Funding Period: 2006-2011 Title: Training in Cellular and Molecular Mechanisms of Tumor Rejection Agency: NIH Role: P.I. Funding Period: 2004-2009 Title: Immune Markers of Permalignant Disease Consortium Agency: Dana Foundation Role: P.I. Funding Period: 2004-2008 Title: MUC-1 related cancer immunity Agency: NIH Role: Co-P.I. Funding Period: 2006-2011 Title: In Vivo PIB Amyloid: Imaging Normals, MCI & Dementia Agency: NIH Role: Co-investigator Funding Period: 2008-2010 Title: MUC1 vaccines for the prevention of colitis-associated colon cancer Agency: Cancer Research and Prevention Foundation Role: Co-investigator Funding Period: 2007-2009           Lab Personnel     Research Associates John McKolanis, Ph.D. Sharmila Pejawar-Gaddy, Ph.D. Postdoctoral Scholar Kira Gantt, Ph.D. Postdoctoral Associates Xiaochuan Chen, Ph.D. Katja Engelmann, Ph.D. Anna Furr, Ph.D. Andrew Lepisto, Ph.D. Staff Scientist Pamela Beatty, Ph.D. Research III Jia Xue Visiting Scholar Lixin Zhang, M.D., Ph.D. Graduate Student Researchers Sean Ryan Laura Vella Trainee Ning Wang           Click here for University of Pittsburgh Interdisciplinary Biomedical Graduate Program Website