University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Alexander Marson, MD, PhD

Alexander Marson, MD, PhD

Assistant Professor, Departments of Microbiology/Immunology and Medicine, UCSF
Chan Zuckerberg Biohub Investigator

Cancer Center Program Memberships

Cancer Immunology

Research Summary

Our lab's goal is to understand the genetic circuits that control human immune cell function in health and disease. We have begun to identify how genetic risk variants for autoimmune diseases disrupt immune cell circuits (Farh and Marson et al., Nature 2015; Simeonov et al., Nature, 2017), and how pathogenic circuits may be targeted with novel therapeutics (Xiao et al., Immunity 2014). My lab has developed new tools for efficient CRISPR genome engineering in primary human T cells (Schumann et al., PNAS 2015; Roth et al., Nature 2018). Now we are pursuing a comprehensive strategy to test how coding and non-coding genetic variation control essential programs in the human immune system. Genome engineered human T cells hold great potential for the next generation of cell-based therapies for cancer, autoimmunity and infectious diseases.

Education

Harvard College, MA, A.B., 2001, Biology
Cambridge University, UK, M.Phil., 2003, Biological Sciences
Massachusetts Institute of Technology, MA, Ph.D., 2008, Biology
Harvard Medical School, MA, M.D., 2010, Medicine
Brigham and Women’s Hospital, Residency, 2012, Internal Medicine
UC San Francisco, Fellowship, Present, Infectious Diseases


Professional Experience

  • 2001-2002
    M.Phil. Lab of Dr. Ashok Venkitaraman, University of Cambridge, UK
  • 2002-2010
    M.D./Ph.D. Student, Labs of Richard Young and Rudolf Jaenisch, Harvard /MIT
  • 2009-2010
    Research with Dr. Richard Young and Dr. David Hafler, Whitehead Institute/MIT
  • 2010-2012
    Visiting Scientist, Laboratory of Vijay Kuchroo, Brigham and Women’s Hospital
  • 2010-2012
    Intern and Resident in Internal Medicine, Brigham and Women’s Hospital
  • 2012
    Clinical Fellow, Division of Infectious Diseases, Department of Medicine, UCSF
  • 2013-2016
    UCSF Sandler Faculty Fellow, Diabetes Center and Department of Medicine, UCSF
  • 2014-present
    Affiliate Member, Innovative Genomics Initiative (IGI), UC Berkeley
  • 2015-present
    Assistant Professor, Departments of Microbiology/Immunology and Medicine, UCSF
  • 2017-present
    Chan Zuckerberg Biohub Investigator

 

Honors & Awards

  • 1998
    Jacob Wendell Prize for most promising freshman scholar, Harvard College
  • 1998
    Detur Book Prize, Harvard College
  • 2000
    William and Mary Bossert Prize, Harvard College
  • 2001
    Phi Beta Kappa, Harvard College
  • 2001-2002
    Herchel Smith Harvard Scholar, Emmanuel College, Cambridge, UK
  • 2009
    Sigma Xi 2009, MIT
  • 2010
    James Tolbert Shipley Prize for excellence and accomplishment in research, Harvard Medical
  • 2016
    American Society of Clinical Investigation (ASCI) Young Physician Scientist Award
  • 2016
    Burroughs Wellcome Foundation Career Award for Medical Scientists
  • 2016
    NIDA/NIH Avenir New Innovator Award
  • 2017
    Named to first cohort of Chan Zuckerberg Biohub Investigators

Selected Publications

  1. Chen SH, Jang GM, Hüttenhain R, Gordon DE, Du D, Newton BW, Johnson JR, Hiatt J, Hultquist JF, Johnson TL, Liu YL, Burton LA, Ye J, Reichermeier KM, Stroud RM, Marson A, Debnath J, Gross JD, Krogan NJ. CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling. EMBO J. 2018 Aug 30.
    View on PubMed
  2. Roth TL, Puig-Saus C, Yu R, Shifrut E, Carnevale J, Li PJ, Hiatt J, Saco J, Krystofinski P, Li H, Tobin V, Nguyen DN, Lee MR, Putnam AL, Ferris AL, Chen JW, Schickel JN, Pellerin L, Carmody D, Alkorta-Aranburu G, Del Gaudio D, Matsumoto H, Morell M, Mao Y, Cho M, Quadros RM, Gurumurthy CB, Smith B, Haugwitz M, Hughes SH, Weissman JS, Schumann K, Esensten JH, May AP, Ashworth A, Kupfer GM, Greeley SAW, Bacchetta R, Meffre E, Roncarolo MG, Romberg N, Herold KC, Ribas A, Leonetti MD, Marson A. Reprogramming human T cell function and specificity with non-viral genome targeting. Nature. 2018 Jul 11.
    View on PubMed
  3. Abbas AK, Trotta E, R Simeonov D, Marson A, Bluestone JA. Revisiting IL-2: Biology and therapeutic prospects. Sci Immunol. 2018 Jul 06; 3(25).
    View on PubMed
  4. 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. Author Correction: Discovery of stimulation-responsive immune enhancers with CRISPR activation. Nature. 2018 Jun 13.
    View on PubMed
  5. Farboud B, Jarvis E, Roth TL, Shin J, Corn JE, Marson A, Meyer BJ, Patel NH, Hochstrasser ML. Enhanced Genome Editing with Cas9 Ribonucleoprotein in Diverse Cells and Organisms. J Vis Exp. 2018 05 25; (135).
    View on PubMed
  6. Wu CM, Roth TL, Baglaenko Y, Ferri DM, Brauer P, Zuniga-Pflucker JC, Rosbe KW, Wither JE, Marson A, Allen CDC. Genetic engineering in primary human B cells with CRISPR-Cas9 ribonucleoproteins. J Immunol Methods. 2018 Mar 31.
    View on PubMed
  7. Kang HM, Subramaniam M, Targ S, Nguyen M, Maliskova L, McCarthy E, Wan E, Wong S, Byrnes L, Lanata CM, Gate RE, Mostafavi S, Marson A, Zaitlen N, Criswell LA, Ye CJ. Multiplexed droplet single-cell RNA-sequencing using natural genetic variation. Nat Biotechnol. 2018 Jan; 36(1):89-94.
    View on PubMed
  8. Mumbach MR, Satpathy AT, Boyle EA, Dai C, Gowen BG, Cho SW, Nguyen ML, Rubin AJ, Granja JM, Kazane KR, Wei Y, Nguyen T, Greenside PG, Corces MR, Tycko J, Simeonov DR, Suliman N, Li R, Xu J, Flynn RA, Kundaje A, Khavari PA, Marson A, Corn JE, Quertermous T, Greenleaf WJ, Chang HY. Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements. Nat Genet. 2017 Nov; 49(11):1602-1612.
    View on PubMed
  9. Nguyen MLT, Simeonov DR, Marson A. "T-bet"-ing on autoimmunity variants. PLoS Genet. 2017 09; 13(9):e1006924.
    View on PubMed
  10. 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. Discovery of stimulation-responsive immune enhancers with CRISPR activation. Nature. 2017 09 07; 549(7670):111-115.
    View on PubMed
  11. Rupp LJ, Schumann K, Roybal KT, Gate RE, Ye CJ, Lim WA, Marson A. CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells. Sci Rep. 2017 04 07; 7(1):737.
    View on PubMed
  12. Park RJ, Wang T, Koundakjian D, Hultquist JF, Lamothe-Molina P, Monel B, Schumann K, Yu H, Krupzcak KM, Garcia-Beltran W, Piechocka-Trocha A, Krogan NJ, Marson A, Sabatini DM, Lander ES, Hacohen N, Walker BD. A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors. Nat Genet. 2017 Feb; 49(2):193-203.
    View on PubMed
  13. Hultquist JF, Schumann K, Woo JM, Manganaro L, McGregor MJ, Doudna J, Simon V, Krogan NJ, Marson A. A Cas9 Ribonucleoprotein Platform for Functional Genetic Studies of HIV-Host Interactions in Primary Human T Cells. Cell Rep. 2016 10 25; 17(5):1438-1452.
    View on PubMed
  14. Van Dyken SJ, Nussbaum JC, Lee J, Molofsky AB, Liang HE, Pollack JL, Gate RE, Haliburton GE, Ye CJ, Marson A, Erle DJ, Locksley RM. A tissue checkpoint regulates type 2 immunity. Nat Immunol. 2016 Dec; 17(12):1381-1387.
    View on PubMed
  15. Schumann K, Lin S, Boyer E, Simeonov DR, Subramaniam M, Gate RE, Haliburton GE, Ye CJ, Bluestone JA, Doudna JA, Marson A. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. Proc Natl Acad Sci U S A. 2015 Aug 18; 112(33):10437-42.
    View on PubMed
  16. Marson A, Housley WJ, Hafler DA. Genetic basis of autoimmunity. J Clin Invest. 2015 Jun; 125(6):2234-41.
    View on PubMed
  17. DuPage M, Chopra G, Quiros J, Rosenthal WL, Morar MM, Holohan D, Zhang R, Turka L, Marson A, Bluestone JA. The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation. Immunity. 2015 Feb 17; 42(2):227-238.
    View on PubMed
  18. Farh KK, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, Shoresh N, Whitton H, Ryan RJ, Shishkin AA, Hatan M, Carrasco-Alfonso MJ, Mayer D, Luckey CJ, Patsopoulos NA, De Jager PL, Kuchroo VK, Epstein CB, Daly MJ, Hafler DA, Bernstein BE. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature. 2015 Feb 19; 518(7539):337-43.
    View on PubMed
  19. Kofler DM, Marson A, Dominguez-Villar M, Xiao S, Kuchroo VK, Hafler DA. Decreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells. J Clin Invest. 2014 Jun; 124(6):2513-22.
    View on PubMed
  20. Xiao S, Yosef N, Yang J, Wang Y, Zhou L, Zhu C, Wu C, Baloglu E, Schmidt D, Ramesh R, Lobera M, Sundrud MS, Tsai PY, Xiang Z, Wang J, Xu Y, Lin X, Kretschmer K, Rahl PB, Young RA, Zhong Z, Hafler DA, Regev A, Ghosh S, Marson A, Kuchroo VK. Small-molecule ROR?t antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms. Immunity. 2014 Apr 17; 40(4):477-89.
    View on PubMed

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