Lawrence P. Kane, PhD
Campus: 200 Lothrop St
Office: E1054 BSTWR
Lab: BSTWR E-10002B-4A
Pittsburgh, PA 15261
- 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
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. The role of TIM-1 in T cell activation and differentiation
Dr. Kane is also studying the role of another TIM family member - TIM-1. Dr. Kane’s lab has found that TIM-1 can provide a co-stimulatory signal, along with the TCR, that affects T cell activation and differentiation. They 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.
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.
Phong BL, Avery L, Menk A, Delgoffe G and Kane LP (2016) Murine mast cells rapidly modulate metabolic pathways essential for distinct effector functions. J. Immunol - Cutting Edge. In Press.
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. In Press.
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. In Press. * 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.