The primary experimental system utilized by the laboratory is the differentiation of helper T cells. Their distinct cellular identities (Th1, Th2, etc.) and associated functions are defined by characteristic gene expression programs. We and many others have documented how these programs are controlled by transcription factors, the cis-regulatory DNA elements to which they bind, and epigenetic modifications that constrain chromatin accessibility at those sites.

More recently, we found that the endogenous RNA interference (RNAi) pathway also regulates helper T cell differentiation, as naive T cells lacking Dicer exhibit rapid, unrestrained differentiation into effector cells. MicroRNAs (miRNA) are the best-characterized class of natural short regulatory RNAs. As they differentiate, T cells reset their miRNA repertoire. This rapid change in miRNA expression may be important to allow T cells to change their gene expression programs and develop effector functions.

The major research goals of our laboratory are: i) to define the molecular mechanisms that control miRNA turnover and determine how this process is accelerated in activated lymphocytes; ii) to characterize the expression and function of noncoding RNAs, including miRNAs, in T cell differentiation, and iii) to extend our work beyond in vitro and mouse models to explore how chromatin remodeling and regulatory RNAs contribute to the pathogenic properties of T cells in human asthma.

Djuretic IM, Levanon D, Negreanu V, Groner Y, Rao A, Ansel KM. T-bet and Runx3 cooperate to activate Ifng and silence Il4 in Th1 cells. Nat. Immunol. 8:145-53 (2007)

Ansel KM, Djuretic I, Tanasa B, Rao A. Regulation of Th2 differentiation and the IL4 locus. Annu. Rev. Immunol. 24:607-56 (2006)

*Monticelli S, *Ansel KM, *Xiao C, *Socci ND, Krichevsky AM, Thai, T-H, Rajewsky N, Marks DS, Sander C, Rajewsky K, Rao A, Kosik KS. MicroRNA profiling of the murine hematopoietic system. Genome Biol. 6:R71 (2005) (*equal contribution)

*Muljo SA, *Ansel KM, *Kanellopoulou C, Livingston DM, Rao A, Rajewsky K. Aberrant T cell differentiation in the absence of Dicer. J. Exp. Med. 202:261-9 (2005).
(*equal contribution)

Ansel KM, Greenwald RJ, Agarwal SA, Bassing CH, Monticelli S, Interlandi J, Djuretic IM, Lee DU, Sharpe AH, Alt FW, Rao A. Deletion of a conserved Il4 silencer impairs Th1-mediated autoimmunity. Nat Immunol. 5:1251-9 (2004)