Patrick E. Fields, PhD
Pathology and Laboratory Medicine
PhD, University of Chicago, 1998
Postdoctoral, Yale University, 1999-2005
Work in our laboratory is focused on the mechanisms of T cell activation and differentiation as they relate to immunological tolerance and disease. Specifically, we are interested in both membrane-proximal and -distal (nuclear) events regulating the gene expression involved in cell fate decisions during peripheral T cell differentiation. These studies will facilitate our long-term goal, which is to understand normal T cell function at the molecular level.
A major area of focus in the laboratory is the study of chromatin remodeling in the regulation of cytokine gene expression during Th1/Th2 differentiation. We recently identified a locus control region (LCR), which regulates gene expression in the Th2 cytokine locus. LCRs are regulatory elements that are thought to control gene expression by among other mechanisms, regulating the accessibility of gene promoters to transcriptional machinery. We will use genetic and molecular biology approaches to study the mechanism by which this LCR functions.
The study of membrane-proximal signaling will focus on the regulation of the Ras/MAP kinase pathway by a novel family of negative feedback inhibitors that are induced by T cell receptor stimulation. The members of this gene family show different patterns of expression in T cells and their expression changes dramatically upon T cell activation and differentiation. Preliminary studies have revealed that these gene products may mediate cell fate decisions by regulating cell survival and differentiation. These studies will be extended by using genetic (knockout and transgenics) as well basic molecular biology and biochemical approaches to examine the role of this gene family in the immune response.
Copeland JN, Feng Y, Neradugomma NK, Fields PE, Vivian JL. Notch signaling regulates remodeling and vessel diameter in the extraembryonic yolk sac. BMC Dev Biol. 2011 Feb 25;11:12.
Feng Y, Yang Y, Ortega MM, Copeland JN, Zhang M, Jacob JB, Fields TA, Vivian JL, Fields PE. Early mammalian erythropoiesis requires the Dot1L methyltransferase. Blood. 2010 Nov 25;116(22):4483-91.
Rossol-Allison J, Stemmle LN, Swenson-Fields KI, Kelly P, Fields PE, McCall SJ, Casey PJ, Fields TA. Rho GTPase activity modulates Wnt3a/beta-catenin signaling. Cell Signal. 2009 Nov;21(11):1559-68.
Kim ST, Fields PE, Flavell RA. Demethylation of a specific hypersensitive site in the Th2 locus control region. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17052-7.
Fields PE, Lee GR, Kim ST, Bartsevich VV, Flavell RA. Th2-specific chromatin remodeling and enhancer activity in the Th2 cytokine locus control region. Immunity. 2004 Dec;21(6):865-76.
Lee GR, Kim ST, Spilianakis CG, Fields PE, Flavell RA. T helper cell differentiation: regulation by cis elements and epigenetics. Immunity. 2006 Apr;24(4):369-79.
Fields PE, Kim ST, Flavell RA. Changes in histone acetylation at the IL-4 and IFN-gamma loci accompany Th1/Th2 differentiation. J Immunol. 2002 Jul 15;169(2):647-50.
Peterson AC, Marks RE, Fields PE, Imamoto A, Gajewski TF. T cell development and function in CrkL-deficient mice. Eur J Immunol. 2003 Oct;33(10):2687-95.
Lee GR, Fields PE, Griffin TJ, Flavell RA. Regulation of the Th2 cytokine locus by a locus control region. Immunity. 2003 Jul;19(1):145-53.