Penelope A. Morel, MD
- Professor, Department of Immunology
- Professor, Department of Medicine, Division of Rheumatology and Clinical Immunology
Education & Training
- MD in Immunology, University of Geneva, 1983
- BM in Medicine, University of Southampton Medical School, 1979
Our research is focused on the control of the T cell immune response and we are particularly interested in the factors that determine the differentiation of specific Th cell subsets, including T regulatory cells (Treg). This general area of research is being pursued in the several related projects. We have identified TCR signal strength as a major determinant of Th cell fate. TCR signals via the Akt/mTOR pathway play an important role in Treg differentiation. We have shown that RNA processing factors are differentially phosphorylated by Akt during Th and Treg differentiation. At present, we are examining the role of RNA processing factors in Treg differentiation using novel mutant mice that we have generated.
We also use mathematical modeling to provide insight on how the TCR signaling pathway determines cell fate. This multidisciplinary project studies the important factors necessary to drive Treg and Th cell differentiation using a novel computer model. Predictions from the model are tested experimentally using T cells from TCR transgenic mice, analysis of signaling events and the tracking of immune responses in vivo.
Morel PA. 2018. Differential T cell signals for T helper cell programming. Immunology. 155: 63-71.
Hawse WF, Boggess WC and Morel PA. 2017. TCR signal strength regulates Akt substrate specificity to induce alternate murine Th and T regulatory cell differentiation programs. J Immunol. 199: 589-597.
Hawse WF, Sheehan RP, Miskov-Zivanov N, Menk NV, Kane LP, Faeder JR and Morel PA. 2015. Cutting Edge: Differential regulation of PTEN by TCR, Akt and FoxO1 controls CD4+ T cell fate decisions. J Immunol. 194: 4615-4619.
Turner MS, Isse K, Fischer DK, Turnquist HR and PA Morel. 2014. Low TCR signal strength induces combined expansion of Th2 and regulatory T cell populations that protect mice from the development of type 1 diabetes. Diabetologia. 57: 1428-1436.
Miskov-Zivanov N, Turner MS, Kane LP, Morel PA* and Faeder JR*. 2013. The duration of T cell stimulation is a critical determinant of cell fate and plasticity. Sci Signal. 6: ra97. doi: 10.1126/scisignal.2004217