Patrick Fields

Research

Overview

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.