Learn more about three major research areas in the Ansel laboratory:
1) MicroRNA homeostasis and Extracellular RNA
2) MicroRNA regulation of helper T cell differentiation and immune effector functions
3) Molecular and cellular analysis of human asthma
Lymphocyte lineage decisions are critical for the development of protective immunity against a great diversity of pathogens, but improper or exaggerated responses also contribute to the development and pathology of autoimmune diseases, chronic inflammation, allergy, and asthma. The Ansel lab's primary experimental system is the differentiation of the central coordinators of adaptive immune responses -- helper T cells. Their distinct cellular identities (Th1, Th2, Th17, 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.
Most of our current work focuses on microRNA (miRNA) regulation of helper T cell behavior and immune function, and how immunogenic stimuli regulate miRNAs homeostasis. Naive CD4+ T cells that cannot produce any miRNAs exhibit reduced cell division and survival in response to immune stimuli. Surprisingly, they also undergo rapid unrestrained differentiation into effector cells. One of the goals of our research is to determine which specific miRNAs regulate each of these T cell behaviors, and which protein coding mRNAs they target to exert their effects. In addition, we learned that T cells rapidly reset their miRNA repertoire upon activation. This rapid change in miRNA expression may be important to allow T cells to change their gene expression programs and develop effector functions.