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 co-founder 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, 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 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 small 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 cis-regulatory 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 define the molecular mechanisms that control miRNA homeostasis and extracellular release by lymphocytes, and determine how the miRNA repertoire is so dramatically remodeled during activation.
Selected Publications:
  1. 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 Keuren-Jensen 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
  2. 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
  3. 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
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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)
  10. 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)
  11. Baumjohann D and Ansel KM. MicroRNA regulation of T cell differentiation and plasticity. Nat Rev. Immunol. 13:666-78 (2013)
  12. 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)
  13. Bronevetsky YB and Ansel KM. Regulation of miRNA biogenesis and turnover in the immune system. Immunol Rev. 253:304-16 (2013)
  14. Bronevetsky Y, Villarino AV, Eisley C, Barbeau R, Barczak A, Heinz GA, Kremmer E, Heissmeyer V, McManus MT, Erle DJ, Rao A, Ansel KM. T cell activation induces proteasomal degradation of Argonaute and rapid remodeling of the microRNA repertoire. J Exp Med. 210:417-32 (2013)
  15. 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)
  16. 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)
  17. Thomas MF, Abdul-Wajid S, Panduro M, Babiarz JE, Rajaram M, Woodruff P, Lanier LL, Heissmeyer V, Ansel KM. Eri1 regulates microRNA homeostasis and mouse lymphocyte development and anti-viral function. Blood. 120:130-42 (2012)
  18. 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).
  19. 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)
  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)