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 T cells and mast 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 T cell and mast cell function. Previous studies have suggested that TIM-3 has different effects on these two cell types, i.e. down-regulation of Th1 T cell function and upregulation of myeloid cell function. Among other things, they are interested in elucidating signaling pathways downstream of TIM-3 in these two cell types.
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.
3. Regulation of mTOR activation by Carma1 and MALT1
Dr. Kane and his lab recently elucidated a previously unappreciated connection between the proteins Carma1 and MALT1 and the mTOR pathway, the latter of which was thought to be controlled solely by a PI3K/Akt dependent mechanism. His lab is now working to further define this pathway and its consequences for T cell activation and differentiation.
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.
Nau N, Horzempa J, O'Dee D, Brown M, Russo B, Hernandez A, Dillon S, Chen J, Kane LP, Sanker S, Hukriede N. (2019) A predicted Francisella tularensis DXD-motif glycosyltransferase blocks immune activation. Virulence. 10:643-656. PMID:31314675.
Carroll K, Avery L, Treat B, Kane LP, Kinchington P, Hendricks R, St. Leger, A. (2019). Differential Expression of Immune Checkpoint Molecules on CD8+ T Cells Specific for Immunodominant and Subdominant Herpes Simplex Virus 1 Epitopes. J Virology. In Press.
DeRiso EA, Szymczak-Workman AL, Montecalvo A, Murphy JM, Seminario M-C, Kane LP* and Bunnell SC* (2019) Polyubiquitin-dependent recruitment of NEMO/IKKγ into T cell receptor signaling microclusters. bioRxiv. doi: https://doi.org/10.1101/617126
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.
Avery L, Filderman J, Szymczak-Workman AL and Kane LP (2018) Tim-3 co-stimlulation promotes short-lived effector T cells, restricts memory precursors and is dispensable for T cell exhaustion. Proc. Natl. Acad. Sci. 115(10):2455-2460. PMC5877951.
Phong BL, Avery L, Menk A, Delgoffe G and Kane LP (2017) Murine mast cells rapidly modulate metabolic pathways essential for distinct effector functions. J. Immunol - Cutting Edge. 198:64-644. PMC5225044.
Shayan G, Srivastava R, Li J, Schmitt N, Kane LP, and Ferris RL (2016) Adaptive Resistance to Anti-PD1 Therapy by Tim-3 Upregulation is Mediated by the PI3K-Akt Pathway in Head and Neck Cancer. OncoImmunology. 22;5(10):e1200778. PMC5283618.
Li J, Shayan G, Avery L, Jie H-B, Gildener-Leapman N, Schmitt N, Lu B, *Kane LP and *Ferris RL. (2016) Tumor-infiltrating Tim-3+ T cells proliferate avidly except when PD-1 is co-expressed: evidence for intracellular cross talk. OncoImmunology. 22;5(10):e1200778. PMC5087305 * Co-corresponding authors.
Phong BL, Avery L, Sumpter TL, Gorman JV, Watkins SC, Colgan JD and Kane LP. (2015) Tim-3 enhances FceRI-proximal signaling to modulate mast cell activation. J. Exp. Med. 212:2289-2304. PMC4689164.
Hamilton KS, Phong B, Cory C, Cheng J, Gorentla B, Zhong X, Shiva S and Kane LP. (2014) A Carma1/MALT1-dependent, Bcl10-independent, pathway regulates antigen receptor-mediated mTOR signaling in T cells. Science Signaling. 7(329):ra55. PMID: 24917592. PMC in process
Cheng J, Hamilton KS and Kane LP. (2014) Phosphorylation of Carma1, but not Bcl10, by Akt regulates TCR/CD28-mediated NF-κB induction and cytokine production. Molecular Immunology. 15:110-116. PMID: 24548923. PMC in process.
DeFrances MC, Debelius DR, Cheng J and Kane LP. (2012) Inhibition of T-Cell Activation by PIK3IP1. Eur. J. Immunol. 42:2754-2759. PMC3654810.
Lin J, Chen L and Kane LP. (2012) Murine Tim-1 is excluded from the immunological synapse. [v1; ref status: Indexed, http://f1000r.es/OaEfdg]. F1000 Research 1:10 (doi: 10.3410/f1000research.1-10.v1). PMC3938182.
Cheng J, Phong B, Wilson DC, Hirsch R and Kane LP. (2011) Akt fine-tunes NF-kB-dependent gene expression during T cell activation. J Biol Chem. 286:36076-36085. PMC3195567.
Lee J, Su EW, Zhu C, Hainline S, Phuah J, Moroco JA, Smithgall TE, Kuchroo VK and Kane LP. (2011) Phosphotyrosine-Dependent Coupling of Tim-3 to TCR Signaling Pathways. Mol Cell Biol. 31:3963–3974. (Featured in the commentary “Driven to Exhaustion?” Science Signaling 4:ec262). PMC3187355.
Su EW, Bi S and Kane LP. (2010) Galectin-9 Regulates T Helper Cell Function Independently of Tim-3. Glycobiology. 21:1258-1265.
De Souza AJ, Oak JS, Jordanhazy R, Fruman DA and Kane LP. (2008) Tim-1-mediated T cell activation requires recruitment and activation of PI 3-kinase. J. Immunol. 180:6518-6526.
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-êB 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.