Department of Immunology at University of Pittsburgh

University of Pittsburgh	UPMC	Health Sciences @ Pitt	School of Medicine

	Department of Immunology

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Flow Facility

E1040
Thomas E. Starzl Biomedical Science Tower
Phone: 412-383-9737
Fax: 412-383-8098

Faculty

	Lawrence P. Kane , Ph.D. Associate Professor E1056 BSTWR 200 Lothrop St. Pittsburgh, PA 15261 Phone: 412.648.8947 Email: lkane@pitt.edu Fax: 412.383.8096 Faculty Research Interests

Research Interests
My lab is currently pursuing several projects: 1. The role of TIM-1 in T cell activation and differentiation This project currently involves the study of TIM-1, a novel protein of the T cell immunoglobulin and mucin domain family. We have found that TIM-1 can provide a co-stimulatory signal, along with the TCR, that affects T cell activation and differentiation. We are trying to determine what signaling pathways are activated by TIM-1 as well as performing structure/function studies to determine how TIM-1 couples to these pathways. 2. The role of TIM-3 in T cells and dendritic cells We are also studying the role of another TIM family member - TIM-3 - in regulation of T cell and dendritic cell function. Previous studies have suggested that TIM-3 has different effects on these two cell types, i.e. downgregulation of Th1 T cell function and upregulation of dendritic cell function. Among other things, we are interested in elucidating signaling pathways downstream of TIM-3 in these two cell types. 3. Activation of NF-kB by the Akt kinase We found that Akt can induce NF-kB-dependent transcription, in cooperation with signals from PKC. We are currently working to identify direct targets of Akt in this pathway, as well as its consequences for T cell activation and CD28 co-stimulation.

Education
B.S. - Boston College (1988) Ph.D. - University of California at San Diego (1996) Postdoc - University of California at San Francisco (1996-2000)

Academic Affiliation
Associate Professor, Department of Immunology, University of Pittsburgh School of Medicine Director, Immunology Graduate Program

Selected Publications
De Souza AJ, Oak JS, Jordanhazy R, Fruman DA, Kane LP. Tim-1-mediated T cell activation requires recruitment and activation of PI 3-kinase. J Immunol, In press. 2008. Anderson AC, Anderson DE, Bregoli L, Hastings WD, Kassam N, Lei C, Chandwaskar R, Karman J,, Su EW, Hirashima M, Bruce JN, Kane LP, Kuchroo VK and Hafler DA. TIM-3 is expressed by cells of the innate immune system and promotes tissue inflammation. Science 318:1141-1143. 2007. de Souza AJ, Kane LP. Immune regulation by the TIM gene family. Immunol Res 36:147-155. 2006. Knickelbein J, de Souza AJ, Narayan P, Tosti R, Kane LP. Cutting Edge: Inhibition of T cell activation by TIM-2. J Immunol 177:4966-4970. 2006. Narayan P, Holt B, Tosti R, Kane LP. CARMA1 is required for Akt-mediated NF-κB activation in T cells. Mol Cell Biol 26:2327-2336. 2006. De Souza AJ, Oriss TB, O’Malley K, Ray A, Kane LP. TIM-1 is expressed on in vivo-activated T cells and provides a co-stimulatory signal for IL-4 expression. Proc Natl Acad Sci 102:17113-171118. 2005. Kane LP, Watkins SC. Dynamic regulation of Tec kinase localization in membrane-proximal vesicles of a T cell clone revealed by TIRF and confocal microscopy. J Biol Chem 280:21949-21954. 2005. Kane LP, Mollenauer MN, Weiss A. A proline-rich motif in the carboxy terminus of Akt contributes to its localization in the immunological synapse. J Immunol 172:5441-5449. 2004. PubMed Link

Grants
Title: Regulation of T Cell Activation and Differentiation by TIM-1 Agency: NIH Role: P.I. Funding Period: 2007-2012 Title: Regulation of NF-κB by the Akt Kinase Agency: NIH Role: P.I. Funding Period: 2007-2011 Title: TIM Family of Genes: Role in T Cell Immunity and Tolerance Agency: NIH Role: Consultant Funding Period: 2008-2013

Lab Personnel
Graduate Students Judong Lee Jean Lin Wern Su Postdoctoral Fellow Jing Cheng

My Links

Kane Lab Website