Dr. M. Carrie Miceli's research focuses on the molecular basis of T-cell activation and inactivation.
T-cells utilize the T-cell receptor (TCR) to specifically recognize antigen in association with self MHC and to signal one of several distinct responses. Under different circumstances, a T-cell responds to TCR stimulation by proliferating, dying, differentiating along a particular developmental pathway, producing lymphokines, releasing cytotoxic granules or by becoming anergic. Recent data suggest that the nature of the ligand stimulating the TCR as well as the signaling molecules included within the TCR "activation complex" can affect the functional consequences of receptor engagement. While considerable progress has been made in understanding the molecular events responsible for initiating and sending a TCR signal for IL-2 production, it remains unclear which of these events are unique to signals for IL-2 production and which are required to send any signal through the TCR. Recent data suggest that these early signaling events may differ when different functions are being elicited.
Miceli and her colleagues are particularly interested in understanding the molecular requirements for signaling TCR-mediated apoptosis and whether the involvement of alternate T-cell co-receptor molecules might affect different functional consequences of TCR engagement. Their work directly relates to basic mechanisms of immune regulation, signal transduction and oncogenesis.
Selected Cancer-Related Publications:
Round JL, Humphries LA, Tomassian T, Mittelstadt P, Zhang M, Miceli MC. Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors. Nat Immunol. 2007; 8(2): 154-61.
Round JL, Tomassian T, Zhang M, Patel V, Schoenberger SP, Miceli MC. Dlgh1 coordinates actin polymerization, synaptic T cell receptor and lipid raft aggregation, and effector function in T cells. J Exp Med. 2005; 201(3): 419-30.
Patel V, Moran M, Low T, Miceli MC. A molecular framework for two step T cell signaling: Lck SH3 domain mutations discriminate two distinctly regulated lipid raft reorganization events. J Immunol. 2001; 166:754-764.
Chung CD, Patel VP, Moran M, Lewis LA, Miceli MC. Galectin-1 induces partial atez chain phosphorylation and antagonizes processive tcr signal transduction. J Immunol.2000; 65: 3722-3729.
Moran M, Miceli MC. Engagement of gpi-anchored t cell CD48 contributes to tcr signals and cytoskeletal reorganization: a role for lipid rafts in t cell activation. Immunity. 1998; 9:787-796.