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

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. Mahuron KM, Moreau JM, Glasgow JE, Boda DP, Pauli ML, Gouirand V, Panjabi L, Grewal R, Luber JM, Mathur AN, Feldman RM, Shifrut E, Mehta P, Lowe MM, Alvarado MD, Marson A, Singer M, Wells J, Jupp R, Daud AI, Rosenblum MD. Layilin augments integrin activation to promote antitumor immunity. J Exp Med. 2020 Sep 07; 217(9).
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  2. Whitman JD, Hiatt J, Mowery CT, Shy BR, Yu R, Yamamoto TN, Rathore U, Goldgof GM, Whitty C, Woo JM, Gallman AE, Miller TE, Levine AG, Nguyen DN, Bapat SP, Balcerek J, Bylsma SA, Lyons AM, Li S, Wong AW, Gillis-Buck EM, Steinhart ZB, Lee Y, Apathy R, Lipke MJ, Smith JA, Zheng T, Boothby IC, Isaza E, Chan J, Acenas DD, Lee J, Macrae TA, Kyaw TS, Wu D, Ng DL, Gu W, York VA, Eskandarian HA, Callaway PC, Warrier L, Moreno ME, Levan J, Torres L, Farrington LA, Loudermilk RP, Koshal K, Zorn KC, Garcia-Beltran WF, Yang D, Astudillo MG, Bernstein BE, Gelfand JA, Ryan ET, Charles RC, Iafrate AJ, Lennerz JK, Miller S, Chiu CY, Stramer SL, Wilson MR, Manglik A, Ye CJ, Krogan NJ, Anderson MS, Cyster JG, Ernst JD, Wu AHB, Lynch KL, Bern C, Hsu PD, Marson A. Evaluation of SARS-CoV-2 serology assays reveals a range of test performance. Nat Biotechnol. 2020 Aug 27.
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  3. Dong R, Libby KA, Blaeschke F, Fuchs W, Marson A, Vale RD, Su X. Rewired signaling network in T cells expressing the chimeric antigen receptor (CAR). EMBO J. 2020 Jul 09; e104730.
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  4. Whitman JD, Hiatt J, Mowery CT, Shy BR, Yu R, Yamamoto TN, Rathore U, Goldgof GM, Whitty C, Woo JM, Gallman AE, Miller TE, Levine AG, Nguyen DN, Bapat SP, Balcerek J, Bylsma SA, Lyons AM, Li S, Wong AW, Gillis-Buck EM, Steinhart ZB, Lee Y, Apathy R, Lipke MJ, Smith JA, Zheng T, Boothby IC, Isaza E, Chan J, Acenas DD, Lee J, Macrae TA, Kyaw TS, Wu D, Ng DL, Gu W, York VA, Eskandarian HA, Callaway PC, Warrier L, Moreno ME, Levan J, Torres L, Farrington LA, Loudermilk R, Koshal K, Zorn KC, Garcia-Beltran WF, Yang D, Astudillo MG, Bernstein BE, Gelfand JA, Ryan ET, Charles RC, Iafrate AJ, Lennerz JK, Miller S, Chiu CY, Stramer SL, Wilson MR, Manglik A, Ye CJ, Krogan NJ, Anderson MS, Cyster JG, Ernst JD, Wu AHB, Lynch KL, Bern C, Hsu PD, Marson A. Test performance evaluation of SARS-CoV-2 serological assays. medRxiv. 2020 May 17.
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  5. Cortez JT, Montauti E, Shifrut E, Gatchalian J, Zhang Y, Shaked O, Xu Y, Roth TL, Simeonov DR, Zhang Y, Chen S, Li Z, Woo JM, Ho J, Vogel IA, Prator GY, Zhang B, Lee Y, Sun Z, Ifergan I, Van Gool F, Hargreaves DC, Bluestone JA, Marson A, Fang D. CRISPR screen in regulatory T cells reveals modulators of Foxp3. Nature. 2020 06; 582(7812):416-420.
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  6. Roth TL, Li PJ, Blaeschke F, Nies JF, Apathy R, Mowery C, Yu R, Nguyen MLT, Lee Y, Truong A, Hiatt J, Wu D, Nguyen DN, Goodman D, Bluestone JA, Ye CJ, Roybal K, Shifrut E, Marson A. Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies. Cell. 2020 Apr 30; 181(3):728-744.e21.
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  7. 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.
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  8. 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 04 16; 78(2):197-209.e7.
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  9. 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 12 19; 4(24).
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  10. 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 01; 38(1):44-49.
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  11. 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 11 22; 4(41).
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  12. 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.
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  13. 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 08 20; 28(8):2169-2181.e4.
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  14. 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.
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  15. 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.
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  16. 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.
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  17. 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 12; 3(12):974-984.
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  18. 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.
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  19. Simeonov DR, Marson A. CRISPR-Based Tools in Immunity. Annu Rev Immunol. 2019 04 26; 37:571-597.
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  20. 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.
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