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. Selyutina A, Persaud M, Simons LM, Bulnes-Ramos A, Buffone C, Martinez-Lopez A, Scoca V, Di Nunzio F, Hiatt J, Marson A, Krogan NJ, Hultquist JF, Diaz-Griffero F. Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5a Binding to the Viral Core. Cell Rep. 2020 Mar 17; 30(11):3766-3777.e6.
    View on PubMed
  2. Gordon DE, Watson A, Roguev A, Zheng S, Jang GM, Kane J, Xu J, Guo JZ, Stevenson E, Swaney DL, Franks-Skiba K, Verschueren E, Shales M, Crosby DC, Frankel AD, Marson A, Marazzi I, Cagney G, Krogan NJ. A Quantitative Genetic Interaction Map of HIV Infection. Mol Cell. 2020 Feb 17.
    View on PubMed
  3. Lowe MM, Boothby I, Clancy S, Ahn RS, Liao W, Nguyen DN, Schumann K, Marson A, Mahuron KM, Kingsbury GA, Liu Z, Munoz Sandoval P, Rodriguez RS, Pauli ML, Taravati K, Arron ST, Neuhaus IM, Harris HW, Kim EA, Shin US, Krummel MF, Daud A, Scharschmidt TC, Rosenblum MD. Regulatory T cells use arginase 2 to enhance their metabolic fitness in tissues. JCI Insight. 2019 Dec 19; 4(24).
    View on PubMed
  4. Nguyen DN, Roth TL, Li PJ, Chen PA, Apathy R, Mamedov MR, Vo LT, Tobin VR, Goodman D, Shifrut E, Bluestone JA, Puck JM, Szoka FC, Marson A. Polymer-stabilized Cas9 nanoparticles and modified repair templates increase genome editing efficiency. Nat Biotechnol. 2020 Jan; 38(1):44-49.
    View on PubMed
  5. Ng MSF, Roth TL, Mendoza VF, Marson A, Burt TD. Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. Sci Immunol. 2019 Nov 22; 4(41).
    View on PubMed
  6. Calderon D, Nguyen MLT, Mezger A, Kathiria A, Müller F, Nguyen V, Lescano N, Wu B, Trombetta J, Ribado JV, Knowles DA, Gao Z, Blaeschke F, Parent AV, Burt TD, Anderson MS, Criswell LA, Greenleaf WJ, Marson A, Pritchard JK. Landscape of stimulation-responsive chromatin across diverse human immune cells. Nat Genet. 2019 10; 51(10):1494-1505.
    View on PubMed
  7. 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 20; 28(8):2169-2181.e4.
    View on PubMed
  8. Leenay RT, Aghazadeh A, Hiatt J, Tse D, Roth TL, Apathy R, Shifrut E, Hultquist JF, Krogan N, Wu Z, Cirolia G, Canaj H, Leonetti MD, Marson A, May AP, Zou J. Large dataset enables prediction of repair after CRISPR-Cas9 editing in primary T cells. Nat Biotechnol. 2019 09; 37(9):1034-1037.
    View on PubMed
  9. Hüttenhain R, Xu J, Burton LA, Gordon DE, Hultquist JF, Johnson JR, Satkamp L, Hiatt J, Rhee DY, Baek K, Crosby DC, Frankel AD, Marson A, Harper JW, Alpi AF, Schulman BA, Gross JD, Krogan NJ. ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection. Cell Host Microbe. 2019 07 10; 26(1):86-99.e7.
    View on PubMed
  10. Mintz MA, Felce JH, Chou MY, Mayya V, Xu Y, Shui JW, An J, Li Z, Marson A, Okada T, Ware CF, Kronenberg M, Dustin ML, Cyster JG. The HVEM-BTLA Axis Restrains T Cell Help to Germinal Center B Cells and Functions as a Cell-Extrinsic Suppressor in Lymphomagenesis. Immunity. 2019 08 20; 51(2):310-323.e7.
    View on PubMed
  11. Schober K, Müller TR, Gökmen F, Grassmann S, Effenberger M, Poltorak M, Stemberger C, Schumann K, Roth TL, Marson A, Busch DH. Orthotopic replacement of T-cell receptor a- and ß-chains with preservation of near-physiological T-cell function. Nat Biomed Eng. 2019 Dec; 3(12):974-984.
    View on PubMed
  12. Simeonov DR, Brandt AJ, Chan AY, Cortez JT, Li Z, Woo JM, Lee Y, Carvalho CMB, Indart AC, Roth TL, Zou J, May AP, Lupski JR, Anderson MS, Buaas FW, Rokhsar DS, Marson A. A large CRISPR-induced bystander mutation causes immune dysregulation. Commun Biol. 2019; 2:70.
    View on PubMed
  13. Simeonov DR, Marson A. CRISPR-Based Tools in Immunity. Annu Rev Immunol. 2019 Apr 26; 37:571-597.
    View on PubMed
  14. Van Gool F, Nguyen MLT, Mumbach MR, Satpathy AT, Rosenthal WL, Giacometti S, Le DT, Liu W, Brusko TM, Anderson MS, Rudensky AY, Marson A, Chang HY, Bluestone JA. A Mutation in the Transcription Factor Foxp3 Drives T Helper 2 Effector Function in Regulatory T Cells. Immunity. 2019 02 19; 50(2):362-377.e6.
    View on PubMed
  15. Owen DL, Mahmud SA, Sjaastad LE, Williams JB, Spanier JA, Simeonov DR, Ruscher R, Huang W, Proekt I, Miller CN, Hekim C, Jeschke JC, Aggarwal P, Broeckel U, LaRue RS, Henzler CM, Alegre ML, Anderson MS, August A, Marson A, Zheng Y, Williams CB, Farrar MA. Thymic regulatory T cells arise via two distinct developmental programs. Nat Immunol. 2019 02; 20(2):195-205.
    View on PubMed
  16. Hultquist JF, Hiatt J, Schumann K, McGregor MJ, Roth TL, Haas P, Doudna JA, Marson A, Krogan NJ. CRISPR-Cas9 genome engineering of primary CD4+ T cells for the interrogation of HIV-host factor interactions. Nat Protoc. 2019 01; 14(1):1-27.
    View on PubMed
  17. Shifrut E, Carnevale J, Tobin V, Roth TL, Woo JM, Bui CT, Li PJ, Diolaiti ME, Ashworth A, Marson A. Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function. Cell. 2018 12 13; 175(7):1958-1971.e15.
    View on PubMed
  18. 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 09 14; 37(18).
    View on PubMed
  19. 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 07; 559(7714):405-409.
    View on PubMed
  20. Abbas AK, Trotta E, R Simeonov D, Marson A, Bluestone JA. Revisiting IL-2: Biology and therapeutic prospects. Sci Immunol. 2018 07 06; 3(25).
    View on PubMed

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