Faculty

K. Mark Ansel, Ph.D.

Professor, Department of Microbiology & Immunology
Sandler Asthma Basic Research Center of UCSF

513 Parnassus Avenue
UCSF Box 0414, HSE-1001E
San Francisco, CA 94143

Tel: 415-476-5368
Fax: 415-502-4995

Websites: 
Ansel Lab 
Biomedical Sciences Graduate Program

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. He is a cofounder of the Bakar ImmunoX Initiative, a new UCSF initiative to harness immunology to improve human health. In addition, he serves as Faculty Director of the UCSF Biomedical Sciences Graduate Program. His laboratory in the Sandler Asthma Basic Research Center focuses on the regulation of gene expression in the immune system.

MicroRNAs (miRNA), RNA binding proteins (RBP), 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, biochemistry, 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.

Lymphocyte lineage decisions and the deployment of their effector functions are critical for the development of protective immunity against a great diversity of pathogens. 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 defined by characteristic gene expression programs and distinct immune functions. These 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 directed by RBPs 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 focus on cellular and molecular analysis of allergic inflammation in asthma and atopic dermatitis, and the post-transcriptional regulatory networks that program immune cells involved in these diseases. We pioneered the study of miRNAs in immune cell differentiation and effector functions, and continue that work to leverage miRNA biology to uncover gene networks that program the cells that drive allergic airway inflammation in asthma. We also study the fate of miRNAs and other regulatory RNAs in activated T cells and airway epithelial cells, as they are specifically regulated by transcription, processing, degradation and even secretion within extracellular vesicles. Recently, we developed a biochemical method for broadly interrogating the cis-regulatory transcriptome in living cells by mapping protein occupancy genome-wide at near-nucleotide resolution. We hypothesized that RBP occupancy in transcripts would be a marker of cisregulatory activity, and this prediction was supported by a massively parallel reporter assay testing each of these site in primary T cells. We are now using GCLiPP together with other biochemical and genetic data to guide experimental dissection of transcripts involved in airway inflammation and allergic disease.

Lab Objectives:
  1. To characterize the function of RBPs and miRNAs that regulate the pathogenic properties of T cells and other immune cells in human asthma.
  2. To map the cis-regulatory activity of the transcriptome and reveal the trans-acting RNA binding proteins and miRNA mediators of post-transriptional regulation.
  3. To decode the immunologic regulatory networks that control sustatined type 2 airway inflammation in asthma.
Selected Publications:
  1. Gagnon JD, Kageyama R, Shehata HM, Fassett MS, Mar DJ, Wigton EJ, Johansson K, Litterman AJ, Odorizzi P, Simeonov D, Laidlaw BJ, Panduro M, Patel S, Jeker LT, Feeney ME, McManus MT, Marson A, Matloubian M, Sanjabi S, Ansel KM. miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival. Cell Rep. 2019 Aug;28(8):2169-2181.e4
  2. Wigton EJ, DeFranco AL, Ansel KM. Antigen Complexed with a TLR9 Agonist Bolsters c-Myc and mTORC1 Activity in Germinal Center B Lymphocytes. Immunohorizons. 2019 Aug 19;3(8):389-401
  3. Litterman AJ, Kageyama R, Le Tonqueze O, Zhao W, Gagnon JD, Goodarzi H, Erle DJ, Ansel KM. A massively parallel 3' UTR reporter assay reveals relationships between nucleotide content, sequence conservation, and mRNA destabilization. Genome Res. 2019 Jun;29(6):896-906
  4. Gagnon JD, Ansel KM. MicroRNA regulation of CD8(+) T cell responses. Noncoding RNA Investig. 2019 Aug;3. pii: 24
  5. Das S; Extracellular RNA Communication Consortium, Ansel KM, Bitzer M, Breakefield XO, Charest A, Galas DJ, Gerstein MB, Gupta M, Milosavljevic A, McManus MT, Patel T, Raffai RL, Rozowsky J, Roth ME, Saugstad JA, Van KeurenJensen K, Weaver AM, Laurent LC. The Extracellular RNA Communication Consortium: Establishing Foundational Knowledge and Technologies for Extracellular RNA Research. Cell. 2019 Apr 4;177(2):231-242
  6. Pua HH, Happ HC, Gray CJ, Mar DJ, Chiou NT, Hesse LE, Ansel KM. Increased Hematopoietic Extracellular RNAs and Vesicles in the Lung during Allergic Airway Responses. Cell Rep. 2019 Jan 22;26(4):933-944
  7. Fassett MS, Pua HH, Simpson LJ, Steiner DF, Ansel KM. Identification of Functionally Relevant microRNAs in the Regulation of Allergic Inflammation. Methods Mol Biol. 2018;1799:341-351
  8. Durack J, Huang YJ, Nariya S, Christian LS, Ansel KM, Beigelman A, Castro M, Dyer AM, Israel E, Kraft M, Martin RJ, Mauger DT, Rosenberg SR, King TS, White SR, Denlinger LC, Holguin F, Lazarus SC, Lugogo N, Peters SP, Smith LJ, Wechsler ME, Lynch SV, Boushey HA; Bacterial biogeography of adult airways in atopic asthma. Microbiome. 2018 Jun 9;6(1):104
  9. Chiou NT, Kageyama R, Ansel KM. Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation. Cell Rep. 2018 25(12):3356-3370
  10. Singh PB, Pua HH, Happ HC, Schneider C, von Moltke J, Locksley RM, Baumjohann D, Ansel KM. MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation. J Exp Med. 2017 Dec;214(12):3627-43
  11. Montoya MM, Maul J, Singh PB, Pua HH, Dahlström F, Wu N, Huang X, Ansel KM*, Baumjohann D*. A Distinct Inhibitory Function for miR-18a in Th17 Cell Differentiation. J Immunol. 2017 Jul 15;199(2):559-569. (*co-corresponding authors)
  12. Pua HH, Steiner DF, Patel S, Gonzalez JR, Ortiz-Carpena JF, Kageyama R, Chiou NT, Gallman A, de Kouchkovsky D, Jeker LT, McManus MT, Erle DJ, Ansel KM. MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of Regulators of T Helper 2 Cell-Associated Cytokine Production. Immunity. 2016 Apr 19;44(4):821-32
  13. Gordon ED, Simpson LJ, Rios CL, Ringel L, Lachowicz-Scroggins ME, Peters MC, Wesolowska-Andersen A, Gonzalez JR, MacLeod HJ, Christian LS, Yuan S, Barry L, Woodruff PG, Ansel KM, Nocka K, Seibold MA, Fahy JV. Alternative splicing of interleukin-33 and type 2 inflammation in asthma. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):8765-70
  14. Simpson LJ, Patel S, Bhakta NR, Choy DF, Brightbill HD, Ren X, Wang Y, Pua HH, Baumjohann D, Montoya M, Panduro M, Remedios KA, Huang X, Fahy JV, Arron JR, Woodruff PG, and Ansel KM. A miRNA upregulated in asthma airway T cells promotes TH2 cytokine production. Nat Immunol 15:1162-70 (2014)
  15. Seumois G, Chavez L, Gerasimova A, Lienhard M, Omran N, Kalinke L, Vedanayagam M, Ganesan AP, Chawla A, Djukanović R, Ansel KM, Peters B, Rao A, Vijayanand P. Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility. Nat Immunol 15:777-88 (2014)
  16. Baumjohann D, Clingan JM, de Kouchkovsky D, Bannard O, Bluestone JA, Matloubian M, Ansel KM*, Jeker LT*. The microRNA cluster miR-17~92 is essential for follicular helper T cell differentiation. Nat Immunol. 14:840-8 (2013) (*co-corresponding authors)
  17. 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. 1:70-89 (2012)
  18. Solberg OD, Ostrin EJ, Love MI, Peng JC, Bhakta NR, Hou L, Nguyen C, Solon M, Nguyen C, Barczak AJ, Zlock LT, Blagev DP, Finkbeiner WE, Ansel KM, Arron JR, Erle DJ, Woodruff PG. Airway Epithelial miRNA Expression is Altered in Asthma. Am J Respir Crit Care Med. 186:965-74 (2012)
  19. Vijayanand P, Seumois G, Simpson LJ, Abdul-Wajid S, Baumjohann D, Panduro M, Huang X, Interlandi J, Djuretic IM, Brown DR, Sharpe AH, Rao A, Ansel KM. Interleukin-4 Production by Follicular Helper T Cells Requires the Conserved Il4 Enhancer Hypersensitivity Site V. Immunity 36:175-87 (2012)
  20. 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)