K. Mark Ansel, Ph.D.
Department of Microbiology and Immunology
505 Parnassus Ave.
UCSF Box 0414, HSE-201H
San Francisco, CA 94143-0414
Fax: 415-502-4995, 415-476-3939
Dr. Mark Ansel is a Professor in the Department of Microbiology & Immunology. He completed a B.S. in biochemistry at Virginia Tech, a Ph.D. in Biomedical Sciences at UCSF, and postdoctoral training at the Immune Disease Institute at Harvard Medical School. His laboratory in the Sandler Asthma Basic Research Center focuses on the regulation of gene expression in the immune system.
MicroRNAs, transcription factors, and epigenetic regulation shape the gene expression programs that determine cell identity and function. The Ansel lab studies how these molecular mechanisms work together to control lymphocyte development, differentiation, and function in immunity. We use in vitro cell differentiation systems, mouse genetics, disease models, and gene expression analyses in cells from human clinical samples to unravel the regulatory networks that underlie immunity and immune pathology, especially allergy and asthma.
Our primary experimental system is the differentiation of the central coordinators of adaptive immune responses -- helper T cells. Upon immune activation, naïve CD4+ T cells can differentiate into several different helper T cell effectors subtypes (e.g. Th1, Th2, Th17, iTreg, Tfh, etc.). These lineages are defined by their characteristic gene expression programs and mediate distinct immune functions. As such, proper regulation of the lineage decisions of helper T cells critically determines the development of protective immunity against a great diversity of pathogens, and improper or exaggerated responses contribute to the development and pathology of autoimmune diseases, chronic inflammation, allergy, and asthma. We and many others have documented how these gene expression programs are controlled by external factors from other cells and the environment, inducible and lineage-specific transcription factors, the cis-regulatory DNA elements to which they bind, and epigenetic modifications that constrain chromatin accessibility at those sites.
More recently, we have become very interested in the roles played by microRNAs (miRNAs). 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 the miRNAs 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.
1) To define the molecular mechanisms that control miRNA homeostasis, and determine how the miRNA repertoire is so dramatically remodeled during T cell activation.
2) To characterize the function of individual miRNAs that regulate T cell differentiation and immune effector functions.
3) To examine the helper T cells in the blood and inflamed lungs of asthma patients for differences in functional effector subset representation and the expression of miRNAs that may contribute to their pathogenic properties in human asthma.
- Vijayanand P#, Seumois G#, Simpson LJ, Abdul-Wajid S, Huang X, Interlandi J, Djuretic IM, Brown DR, Sharpe AH, Rao A, Ansel KM. IL-4 production by Follicular Helper T cells requires the conserved Il4 enhancer HS V/CNS2. In press at Immunity. (#equal contribution)
- Baumjohann D, Okada T, Ansel KM. Cutting Edge: Distinct Waves of BCL6 Expression during T Follicular Helper Cell Development. J Immunol.187:2089-92 (2011)
- Steiner DF, Thomas MF, Hu JK, Yang Z, Babiarz JE, Allen CD, Matloubian M, Blelloch R, Ansel KM. MicroRNA-29 Regulates T-Box Transcription Factors and Interferon-γ Production in Helper T Cells. Immunity 35:169-81 (2011)
- Sofi MH, Qiao Y, Ansel KM, Kubo M, Chang CH. Induction and Maintenance of IL-4 Expression Are Regulated Differently by the 3' Enhancer in CD4 T Cells. J. Immunol. 186:2792-9 (2011)
- Thomas MF, Ansel KM. Construction of small RNA cDNA libraries for deep sequencing. Methods Mol Biol. 667:93-111 (2010)
- Ansel KM*, Pastor WA, Rath N, Lapan AD, Glasmacher E, Wolf C, Smith LC, Papadopoulou N, Lamperti E, Tahiliani M, Ellwart JW, Shi Y, Kremmer E, Rao A, Heissmeyer V*. Mouse ERI-1 interacts with the ribosome and catalyzes 5.8S rRNA processing. Nat. Struct. Mol. Biol. 15:523-30 (2008) (*corresponding authors)
- Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela D, Kutok JL, Schmidt-Supprian M, Rajewsky N, Yancopoulos G, Rao A, Rajewsky K. Regulation of the germinal center response by microRNA-155. Science 316:604-8 (2007)
- 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)
- *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).
- 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)
- Ansel KM, Lee DU, Rao A. An epigenetic view of helper T cell differentiation. Nat. Immunol. 4:616-23 (2003)