The processes of T-cell development and differentiation are coordinated by a multitude of signaling processes and transcription factors that impart distinct functional properties on progenitors. We have focused on understanding the role of ‘Special AT-rich binding protein 1’ (SATB1) in T-cell development and differentiation. In mice lacking SATB1 thymocyte development is stalled at double-positive (DP) stage suggesting a critical role for SATB1 in thymocyte development. Recent reports from our laboratory and other groups have demonstrated that SATB1 is known to play an important role in the regulation of Interleukin 5 (IL-5) gene locus in peripheral CD4+ T-cells and thereby regulate T-helper 2 (TH2) differentiation. Moreover, we have identified SATB1 as a novel mediator of Wnt signaling such that it can recruit β-catenin onto its targets. T-lymphocyte development and differentiation is a multi-step process that begins in the thymus and completed in the periphery. The sequential development of thymocytes is dependent on T-cell receptor (TCR) signaling and an array of transcription factors. We are interested in studying the cross-talk between such multiple signaling cascades that are important for T- cell development and differentiation.

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The focus of our research is to understand how SATB1 orchestrates the dynamic changes in chromatin architecture and thereby gene expression patterns in a signal- and context-dependent manner. Recent studies from our laboratory have indicated that the expression of SATB1 itself is governed by the Wnt and TCR signaling pathways. We are therefore interested in delineating the molecular mechanisms of regulation of SATB1 during T-cell development and differentiation. The regulation of SATB1 expression and function will be dissected at transcriptional, post-transcriptional, and post-translational levels. As a long-term goal, our genome-wide studies using multiple model systems would provide insights into the context-specific regulation by SATB1.