Lawrence P. Kane, Ph.D.
Campus: The Assembly, 5051 Centre Ave
Pittsburgh, PA 15213
- B.S. - Boston College (1988)
- Ph.D. - University of California at San Diego (1996)
- Postdoc - University of California at San Francisco (1996-2000)
- Professor and Vice Chair for Education, Department of Immunology
My lab is currently pursuing several projects:
1. The role of TIM-3 in CD8+ T cells
This project currently involves the study of - TIM-3, a novel protein of the T cell immunoglobulin and mucin domain family in regulation of CD8+ T cell function during viral infection (using LCMV as a model system) and responses to syngeneic tumors. We are also interested in elucidating signaling pathways downstream of TIM-3.
2. The role of TIM-3 in regulatory T cells (Treg)
Work from our lab and others has shown that expression of TIM-3 is assocated with acquisition of a more potent "effector" Treg (eTreg) phenotype. We are studying how this phenotype contributes to the effects of Treg on immune responses to viral infection and tumors, using both mouse models and correlative studies in humans.
2. Regulation of T cell and mast cell activation by PIK3IP1/TrIP, a novel regulator of PI3K
Dr. Kane's lab has found that a novel transmembrane protein known as PIK3IP1 (PI3K-interacting protein 1) or TrIP (transmembrane inhibitor of PI3K) is expressed in both T cells and mast cells. This protein appears to restrict early activation of both cell types. The lab is currently characterizing mice with inducible deletion of TrIP to better understand how this protein functions in vivo
Pagliano O, Morrison RM, Chauvin JM, Banerjee H, Davar D, Ding Q, Tanegashima T, Gao W, Chakka SR, DeBlasio R, Lowin A, Kara K, Ka M, Zidi B, Amin R, Raphael I, Zhang S, Watkins SC, Sander C, Kirkwood JM, Bosenberg M, Anderson AC, Kuchroo VK, Kane LP, Korman AJ, Rajpal A, West SM, Han M, Bee C, Deng X, Schebye XM, Strop P, Zarour HM. (2022) Tim-3 mediates T cell trogocytosis to limit antitumor immunity. J. Clin. Invest. 132(9):e152864. PMID: 35316223. PMC9057587.
Banerjee H, Nieves-Rosado H, Kulkarni A, Murter B, Chandran U, Chang A, Szymczak Workman AL, Vujanovic L, Ferris RL and Kane LP. (2021) Expression of Tim-3 drives phenotypic and functional changes in Treg in secondary lymphoid organs and the tumor microenvironment. Cell Reports. 36(11):109699. PMID 34525351. PMC8482289.
Kataoka S, Manandhar P, Lee J, Workman CJ, Banerjee H, Szymczak-Workman SL, Kvorjak M, Lohmueller J and Kane LP. (2021) The co-stimulatory activity of Tim-3 requires Akt and MAPK signaling and immune synapse recruitment. Science Signaling. Vol. 14, Issue 687, eaba0717. PMID: 34131021. PMC9741863.
Ottens K, Schneider J, Kane LP, and Satterthwaite AB. (2020) PIK3IP1 promotes extrafollicular class switching in T-dependent immune responses. J. Immunol. 205(8):2100-2108. PMC7541772.
Poholek CH, Raphael I, Wu D, Revu S, Rittenhouse N, Uche UU, Majumder S, Kane LP, Poholek AC, and McGeachy MJ. (2020) Noncanonical STAT3 activity sustains pathogenic Th17 proliferation and cytokine response to antigen. J. Exp. Med. 217(10): e20191761. PMC7537401.
Kim HS, Chang CY, Yoon HJ, Kim KS, Koh HS, Kim SS, Lee S-J, Kane LP and Park EJ. (2020) Glial TIM-3 modulates immune responses in the brain tumor microenvironment. Cancer Res. Feb 24. doi: 10.1158/0008-5472.CAN-19-2834. PMID: 32094297. PMC8188274.
Carroll K, Avery L, Treat B, Kane LP, Kinchington P, Hendricks R, and St. Leger, A. (2020) Differential Expression of Immune Checkpoint Molecules on CD8+ T Cells Specific for Immunodominant and Subdominant Herpes Simplex Virus 1 Epitopes. J Virology. 94(2):e01132-19. PMID: 31645447. PMC6955272.
Hernandez-Mir G, Raphael I, Revu S, Poholek CH, Avery L, Hawse WF, Kane LP, McGeachy MJ. (2019) The Alzheimer's Disease-Associated Protein BACE1 Modulates T Cell Activation and Th17 Function. J. Immunol. 203:665-675. PMID:31209103. PMC6650361.
Uche U, Szymczak-Workman AL, Grebinoski S, Piccirillo A, D’Cruz LM and Kane LP. (2018) PIK3IP1/TrIP restricts activation of T cells through inhibition of PI3K/Akt. J. Exp. Med. 215:3165-3179. PMC6279406.