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    Mark Ansel, PhD

    TitleAssociate Professor
    SchoolUCSF School of Medicine
    DepartmentMicrobiology and Immunology
    Address513 Parnassus Ave
    San Francisco CA 94143

       Education and Training
      University of California, San FranciscoPh.D. Graduate Division (Biomedical Sciences)2001

      Naive lymphocytes that encounter their cognate antigens differentiate into a variety of immune effector cells under the influence of cytokines and other inflammatory stimuli. 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 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.

      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 high dimensional cellular and molecular analyses in human biospecimens to unravel the regulatory networks that underlie immunity and immune pathology, especially allergy and asthma.

      Lymphocyte lineage decisions and the deployment of their effector functions are critical for the development of protective immunity against a great diversity of pathogens. However, improper or exaggerated responses underlie the pathogenesis of autoimmune diseases, chronic inflammation, allergy, and asthma. Our primary experimental system is the differentiation of helper T cells, the central coordinators of adaptive immune responses. 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. These gene expression programs are controlled by external factors that derive from other cells or the environment, signaling-induced and lineage-specific transcription factors, epigenetic regulation of transcriptional responses, and posttranscriptional mechanisms, including RNA-binding proteins and miRNAs. The depth of our knowledge about the networks that control helper T cells makes them an attractive model for studying basic mechanisms of gene regulation.

      Active projects in the laboratory mostly focus on miRNAs. We study how individual miRNA families regulate helper T cell differentiation and immune function, as well as the regulation of the miRNA pathway itself during immune responses. 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. We have developed a screening technology that allows us to rapidly determine which specific miRNAs regulate each of these T cell behaviors, and a high throughput nanoscaled pipeline for determining miRNA expression patterns in small clinical samples (such as sorted T cell subsets from the airways of human asthmatic subjects, serum, sputum, and other sources of extracellular miRNAs, etc.). In addition, we discovered that T cells rapidly reset their miRNA repertoire upon activation. This process that involves ubiquitination and degradation of Argonaute proteins, but the signaling mechanisms and the fate of associated miRNAs remains unknown. 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:

      1) To define the molecular mechanisms that control miRNA homeostasis in lymphocytes, 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 determine how the expression and function of miRNAs contribute to the pathogenic properties of T cells in human asthma.

       ORNG Applications 
       Awarded Grants

      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Baumjohann D, Ansel KM. MicroRNA regulation of the germinal center response. Curr Opin Immunol. 2014 Jun; 28:6-11.
        View in: PubMed PMC4037353
      2. Ansel KM. RNA regulation of the immune system. Immunol Rev. 2013 May; 253(1):5-11.
        View in: PubMed PMC3621022
      3. Seumois G, Vijayanand P, Eisley CJ, Omran N, Kalinke L, North M, Ganesan AP, Simpson LJ, Hunkapiller N, Moltzahn F, Woodruff PG, Fahy JV, Erle DJ, Djukanovic R, Blelloch R, Ansel KM. An integrated nano-scale approach to profile miRNAs in limited clinical samples. Am J Clin Exp Immunol. 2012 Nov 30; 1(2):70-89.
        View in: PubMed
      4. Ansel KM, Pastor WA, Rath N, Lapan AD, Glasmacher E, Wolf C, Smith LC, Papadopoulou N, Lamperti ED, Tahiliani M, Ellwart JW, Shi Y, Kremmer E, Rao A, Heissmeyer V. Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing. Nat Struct Mol Biol. 2008 May; 15(5):523-30.
        View in: PubMed PMC3032500
      5. Brekke JS, Ansel M, Long J, Slade E, Weinstein M. Intensity and continuity of services and functional outcomes in the rehabilitation of persons with schizophrenia. Psychiatr Serv. 1999 Feb; 50(2):248-56.
        View in: PubMed
      6. Brekke JS, Raine A, Ansel M, Lencz T, Bird L. Neuropsychological and psychophysiological correlates of psychosocial functioning in schizophrenia. Schizophr Bull. 1997; 23(1):19-28.
        View in: PubMed
      7. Thibaut M, Ansel M, de Azevedo Carneiro J. Lasers as tools for mycology. Br J Exp Pathol. 1983 Aug; 64(4):403-10.
        View in: PubMed PMC2040789
      8. Thibaut M, Ansel M, Saez H. The application of laser microscopy to the spectrochemical analysis of fungal tissues. Br J Exp Pathol. 1981 Oct; 62(5):446-51.
        View in: PubMed PMC2041707
      9. Thibaut M, Ansel M, de Azevedo Carneiro J. Observations on the chemical compositions of some pathogenic fungi for humans determined by X-ray microanalysis. Folia Histochem Cytochem (Krakow). 1980; 18(4):237-43.
        View in: PubMed
      10. Thibaut M, Ansel M, Carneiro J De A. Study of allergenic fungi by means of a laser beam. Br J Exp Pathol. 1979 Apr; 60(2):180-4.
        View in: PubMed PMC2041442
      11. Thibaut M, Ansel M, de Azevedo Carneiro J. A microanalysis approach to investigate problems encountered in mycology. Am J Pathol. 1978 Jan; 90(1):23-32.
        View in: PubMed PMC2018224
      12. Thibaut M, Ansel M, de Azevedo Carneiro J. X-ray microanalysis as applied to fungal tissues. Br J Exp Pathol. 1977 Apr; 58(2):209-14.
        View in: PubMed PMC2041278
      13. Thibaut M, Ansel M. Chemical analysis of five species of Aspergillus by combined scanning electron microscopy and x-ray spectrometry. Trans Am Microsc Soc. 1976 Apr; 95(2):210-4.
        View in: PubMed
      14. Thibaut M, Ansel M. The use of analytical electron microscopy in the study of three species of Aspergillaceae. Parassitologia. 1975 Jan-Dec; 17(1-3):49-56.
        View in: PubMed
      15. Thibaut M, Ansel M. Advantages of x-ray microanalysis in the field of medical mycology. Acta Trop. 1975; 32(4):353-8.
        View in: PubMed
      16. Ansel M, Thibaut M, Saez H. Scanning electron microscopy on Parascaris equorum (Goeze, 1782), Yorke and Maplestone, 1926. Int J Parasitol. 1974 Feb; 4(1):17-23.
        View in: PubMed
      17. Thibaut M, Ansel M. Mycological applications of x-ray microanalysis. J Bacteriol. 1973 Dec; 116(3):1181-4.
        View in: PubMed PMC246473
      18. Ansel M, Thibaut M. Value of the specific distinction between tascaris lumbricoïdes Linnè 1758 and Ascaris suum Goeze 1782. Int J Parasitol. 1973 May; 3(3):317-9.
        View in: PubMed
      19. Ansel M, Thibaut M. [Differentiation of Syphomycetes species with the electron scanning microscope]. Ann Parasitol Hum Comp. 1973 Mar-Apr; 48(2):387-97.
        View in: PubMed
      20. Thibaut M, Ansel M. [Preliminary observations on Dolichoascus schenckii, sexual form of Sporotrichum schenkii]. Ann Dermatol Syphiligr (Paris). 1973; 100(1):49-53.
        View in: PubMed
      21. Thibaut M, Ansel M. [New description of an ascomycete perithecium]. Ann Parasitol Hum Comp. 1972 Jan-Feb; 47(1):159-67.
        View in: PubMed
      22. Thibaut M, Ansel M. [Use of scanning electron microscope for morphological study of fungi]. Ann Parasitol Hum Comp. 1971 Jan-Feb; 46(1):103-7.
        View in: PubMed
      23. Thibaut M, Ansel M, Lariviere M. [Cytologic aspects of some elements of metabolism in Sporotrichum]. Ann Parasitol Hum Comp. 1970 Jul-Aug; 45(4):497-507.
        View in: PubMed
      24. Ansel M, Thibaut M, Tourte Y. [The lomasomes of Sporotrichum schenckii]. Ann Parasitol Hum Comp. 1969 Nov-Dec; 44(6):797-810.
        View in: PubMed
      25. Lariviere M, Tourte Y, Ansel M, Thibaut M. [Existence of myelinic structures in fungi]. Ann Parasitol Hum Comp. 1969 Jan-Feb; 44(1):107-12.
        View in: PubMed
      26. Ansel M, Thibaut M. [Action of the anti-epileptics on multiplication of parasitic yeast in the digestive tract of man]. Therapie. 1967 Sep-Oct; 22(5):1159-64.
        View in: PubMed
      27. Ansel M, Thibaut M. [Sulfonamides and the multiplication of yeast parasites in man]. Therapie. 1967 Jul-Aug; 22(4):919-25.
        View in: PubMed
      28. Ansel M, Thibaut M. [Action of diverse intestinal antiseptics on the multiplication of yeast parasites of the human digestive tract]. Therapie. 1967 Mar-Apr; 22(2):337-44.
        View in: PubMed
      29. Ansel M, Thibaut M. [Antagonisms between pathogenic yeasts and certain bacteria]. Ann Parasitol Hum Comp. 1967 Jan-Feb; 42(1):65-70.
        View in: PubMed
      30. Ansel M, Thibaut M. [Antifungal action in vitro of mepacrine dihydrochloride]. Therapie. 1965 Jul-Aug; 20(4):1027-31.
        View in: PubMed
        View in: PubMed
        View in: PubMed
      33. ANSEL M, THIBAUT M. [The treatment of histoplasmosis]. Vie Med. 1962 Dec; 43(Spec):109-10.
        View in: PubMed
      34. ANSEL M, THIBAUT M. [Diagnosis of allergies of fungal origin]. Vie Med. 1962 Nov; 43:1629-36.
        View in: PubMed
      35. ANSEL M. [Histoplasmosis]. Vie Med. 1962 Sep; 43:1289-93.
        View in: PubMed
      36. ANSEL M, THIBAUT M. ["Pseudomycoses"--their diagnosis]. Prog Med (Paris). 1961 Jul 10; 89:284-6.
        View in: PubMed
      37. ANSEL M, GILLES R, THIBAUT M. [Definitive treatment by desensitization of recurrent candidiasis]. Rev Prat. 1960 Feb 11; 10:545.
        View in: PubMed
      38. ANSEL M, THIBAUT M. [Phytotherapy of trichomonal vaginitis with Aristolochia clematitis]. Bull Soc Pathol Exot Filiales. 1960 Jan-Feb; 53:39-40.
        View in: PubMed
      39. ANSEL M, CLAY R, GOUDAL H, GROSGOGEAT Y, WORMS R. [Madura foot]. Bull Soc Fr Dermatol Syphiligr. 1956 Jul-Oct; 63(4):314-6.
        View in: PubMed
      40. ANSEL M, GAUTHIER C. [Experimental moniliasis in mice by intraperitoneal injection with mucin; influence of sex]. Ann Parasitol Hum Comp. 1955; 30(3):312-7.
        View in: PubMed
      41. ANSEL M, GAUTHIER C. [Classification of yeasts of the genera Candida and Mycoderma; morphological and physiological characteristics]. Ann Parasitol Hum Comp. 1954; 29(1-2):148-62.
        View in: PubMed
      42. ANSEL M. [Encephalitogenic neurotropic viruses]. Ann Parasitol Hum Comp. 1950; 25(3):221-34; contd.
        View in: PubMed
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