Inflammation involves a complex interplay of biochemical pathways that trigger and shape the immune response. These culminate in a coordinated response that is essential for protection against invading pathogens. Inflammation, if unchecked, can favor the development of chronic inflammatory and autoimmune diseases. Thus, mechanisms that regulate its duration and intensity are fundamental to immune homeostasis. Our research interest is to elucidate the mechanisms that underlie the regulation of inflammation and the homeostatic control of immune function. We have discovered a signaling pathway downstream of the TAM (Tyro3, Axl, Mer) receptor tyrosine kinases that limits the amplitude and phase of the inflammatory response. We are currently focusing on identifying the in vivo source of TAM ligands, unraveling the molecular determinants that account for the specificity of TAM-mediated inhibition, decoding the transcriptome activated during TAM-mediated inhibition of inflammation, and testing the role of TAM-mediated immune suppression in vivo. Our long-term goal is to manipulate this pathway as an innovative therapeutic strategy for the inhibition or enhancement of the inflammatory response.
- Rothlin CV, Carrera-Silva EA, Bosurgi L, Ghosh S. TAM Receptor Signaling in Immune Homeostasis. Annu Rev Immunol. 2015 Jan 14. [Epub ahead of print]
- Kusne Y, Carrera Silva E, Perry AS, Rushing EJ, Mandell EK, Dietrich J, Errasti A, Gibbs D, Berens ME, Loftus JC, Hulme C, Aldape K, Sanai N, Rothlin CV* and Ghosh S*. Tumor intrinsic EGFR and macrophage induced TNF-a signaling cooperate to promote GBM progression through aPKC. * co-corresponding authors. Science Signaling, 2014, 7(338), ra75.
- Rothlin CV, Leighton j, Ghosh S. (2014) TAM receptor signaling in inflammatory bowel disease and colitis-associated cancer. Inflamm Bowel Dis. 20(8): 1472-80. PMID: 24846720
- Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer. Bosurgi L, Bernink JH, Delgado Cuevas V, Gagliani N, Joannas L, Schmid ET, Booth CJ, Ghosh S and Rothlin CV. Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer. Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):13091-6
- Carrera Silva EA, Chan PY, Joannas L, Errasti AE, Gagliani N, Bosurgi L, Jabbour M, Perry A, Smith-Chakmakova F, Mucida D, Cheroutre H, Burstyn-Cohen T, Leighton JA, Lemke G, Ghosh S and Rothlin CV: T Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response. Immunity. 2013 Jul 25;39 (1) :160-70. Epub 2013 Jul 11. PMID: 23850380
- Lemke G and Rothlin C.V. (2008). Immunobiology of the TAM receptors. Nat Rev Immunol 8(5): 327-336
- Rothlin C.V, Ghosh S., Zuniga E., Oldstone M.B., Lemke G.E (2007). TAM receptors are pleiotropic inhibitors of the innate immune response. Cell 131(6): 1124-1136.