Mark Ansel, PhD

Director, Biomedical Sciences Graduate Program
Associate Professor
Department of Microbiology and Immunology
Primary Thematic Area
Secondary Thematic Area
Research Summary
RNA Regulation in the Immune System
Mentorship Development

7/2020-6/2021 - HHMI Mentorship Skills Development 1/12/22 - Equity Based Interview Practices
4/2024 - Supporting Learners in Distress

In the Ansel Lab, we are RNA immunologists working to understand the molecular and cellular underpinnings of the chronic tissue inflammation and dysfunction that manifest in immune-mediated diseases, including infectious disease, autoimmunity, and allergy, especially asthma. RNA is a messenger molecule, tasked with carrying information about the state of a cell and its genome so that internal and external cues can be translated into action. The BioNTech/Pfizer and Moderna SARS-CoV-2 RNA vaccines are a powerful demonstration of the potential of harnessing RNA for the prevention and treatment of human diseases. The Ansel lab has developed novel biochemical and computational techniques to discover the regulatory information encoded in RNA molecules. We use human and mouse genetics to interrogate the function of novel RNA modules in the programming of cell fate and function, with a focus on lymphocytes and epithelial cells. Since it is now clear that RNA can be delivered safely and effectively to cells, engineering these modules for cell reprogramming is a viable and exciting new path for development of therapeutics and customized cell therapies.

Active projects in the laboratory focus on RNA regulation of immune cell programming, and multi-omic analysis of human airway disease. 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.

The major research goals of our laboratory are:

  1. To define the molecular mechanisms that control miRNA homeostasis in lymphocytes, and determine how the microRNA repertoire is so dramatically remodeled during T cell activation.
  2. To discover the interaction networks and biological functions of RNA binding proteins and microRNAs that regulate lymphocytel differentiation and immune effector functions.
  3. To uncover the molecular and cellular circuitry that underlies the immunopathogenesis of asthma and other immune-mediated diseases.

Publications

Tumor cell-adipocyte gap junctions activate lipolysis and contribute to breast tumorigenesis.

Nature communications

Williams J, Camarda R, Malkov S, Zimmerman LJ, Manning S, Aran D, Beardsley A, Van de Mark D, Nakagawa R, Chen Y, Berdan C, Louie SM, Mahieu C, Superville D, Winkler J, Willey E, Hutchins EJ, Gagnon JD, Avsaroglu SK, Shinoda K, Gruner M, Nishida H, Ansel KM, Werb Z, Nomura DK, Kajimura S, Butte AJ, Sanders ME, Liebler DC, Rugo HS, Krings G, Shepherd JA, Goga A

Null and missense mutations of ERI1 cause a recessive phenotypic dichotomy in humans.

American journal of human genetics

Guo L, Salian S, Xue JY, Rath N, Rousseau J, Kim H, Ehresmann S, Moosa S, Nakagawa N, Kuroda H, Clayton-Smith J, Wang J, Wang Z, Banka S, Jackson A, Zhang YM, Wei ZJ, Hüning I, Brunet T, Ohashi H, Thomas MF, Bupp C, Miyake N, Matsumoto N, Mendoza-Londono R, Costain G, Hahn G, Di Donato N, Yigit G, Yamada T, Nishimura G, Ansel KM, Wollnik B, Hrabe de Angelis M, Mégarbané A, Rosenfeld JA, Heissmeyer V, Ikegawa S, Campeau PM

Obesity alters pathology and treatment response in inflammatory disease.

Nature

Bapat SP, Whitty C, Mowery CT, Liang Y, Yoo A, Jiang Z, Peters MC, Zhang LJ, Vogel I, Zhou C, Nguyen VQ, Li Z, Chang C, Zhu WS, Hastie AT, He H, Ren X, Qiu W, Gayer SG, Liu C, Choi EJ, Fassett M, Cohen JN, Sturgill JL, Crotty Alexander LE, Suh JM, Liddle C, Atkins AR, Yu RT, Downes M, Liu S, Nikolajczyk BS, Lee IK, Guttman-Yassky E, Ansel KM, Woodruff PG, Fahy JV, Sheppard D, Gallo RL, Ye CJ, Evans RM, Zheng Y, Marson A

Impaired antibacterial immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19.

medRxiv : the preprint server for health sciences

Tsitsiklis A, Zha BS, Byrne A, Devoe C, Levan S, Rackaityte E, Sunshine S, Mick E, Ghale R, Jauregui A, Sarma A, Neff N, Serpa PH, Deiss TJ, Kistler A, Carrillo S, Ansel KM, Leligdowicz A, Christenson S, Jones N, Wu B, Darmanis S, Matthay MA, Lynch SV, DeRisi JL, COMET Consortium+ , Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Erle DJ, Rosenberg O, Calfee CS, Langelier CR

Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS.

Nature communications

Sarma A, Christenson SA, Byrne A, Mick E, Pisco AO, DeVoe C, Deiss T, Ghale R, Zha BS, Tsitsiklis A, Jauregui A, Moazed F, Detweiler AM, Spottiswoode N, Sinha P, Neff N, Tan M, Serpa PH, Willmore A, Ansel KM, Wilson JG, Leligdowicz A, Siegel ER, Sirota M, DeRisi JL, Matthay MA, COMET Consortium , Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Erle DJ, Calfee CS, Langelier CR

Bacterial biogeography of adult airways in atopic asthma.

Microbiome

Durack J, Huang YJ, Nariya S, Christian LS, Mark Ansel K, 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

Discovery of stimulation-responsive immune enhancers with CRISPR activation.

Nature

Simeonov DR, Gowen BG, Boontanrart M, Roth TL, Gagnon JD, Mumbach MR, Satpathy AT, Lee Y, Bray NL, Chan AY, Lituiev DS, Nguyen ML, Gate RE, Subramaniam M, Li Z, Woo JM, Mitros T, Ray GJ, Curie GL, Naddaf N, Chu JS, Ma H, Boyer E, Van Gool F, Huang H, Liu R, Tobin VR, Schumann K, Daly MJ, Farh KK, Ansel KM, Ye CJ, Greenleaf WJ, Anderson MS, Bluestone JA, Chang HY, Corn JE, Marson A

Biogenesis, delivery, and function of extracellular RNA.

Journal of extracellular vesicles

Patton JG, Franklin JL, Weaver AM, Vickers K, Zhang B, Coffey RJ, Ansel KM, Blelloch R, Goga A, Huang B, L'Etoille N, Raffai RL, Lai CP, Krichevsky AM, Mateescu B, Greiner VJ, Hunter C, Voinnet O, McManus MT

Self-enforcing feedback activation between BCL6 and pre-B cell receptor signaling defines a distinct subtype of acute lymphoblastic leukemia.

Cancer cell

Geng H, Hurtz C, Lenz KB, Chen Z, Baumjohann D, Thompson S, Goloviznina NA, Chen WY, Huan J, LaTocha D, Ballabio E, Xiao G, Lee JW, Deucher A, Qi Z, Park E, Huang C, Nahar R, Kweon SM, Shojaee S, Chan LN, Yu J, Kornblau SM, Bijl JJ, Ye BH, Ansel KM, Paietta E, Melnick A, Hunger SP, Kurre P, Tyner JW, Loh ML, Roeder RG, Druker BJ, Burger JA, Milne TA, Chang BH, Müschen M

Airway epithelial miRNA expression is altered in asthma.

American journal of respiratory and critical care medicine

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