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; Nguyen et al. Nature Biotech 2020). Now we are pursuing a comprehensive strategy to test how coding and non-coding genetic variation control essential programs in the human immune system (Simeonov et al. Nature, 2017; Shifrut et al., Cell 2018; Roth et al., Cell 2020; Cortez et al., Nature 2020; Schumann et al., Nature Immunology 2020). Genome engineered human T cells hold great potential for the next generation of cell-based therapies for cancer, autoimmunity and infectious diseases.

Research Funding

  • September 8, 2020 - August 31, 2025 - Inherited T cell defects: Diagnosis, Mechanisms and Treatments , Principal Investigator . Sponsor: NIH, Sponsor Award ID: P01AI138962
  • September 18, 2018 - May 31, 2022 - Functional Molecular Investigation of Inflammatory Bowel Disease (IBD) Risk Variants , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DK119979
  • September 30, 2016 - May 31, 2021 - Functional Interrogation of Non-Coding Type 1 Diabetes Risk Variants in Human Immune Cells and Beta Cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: DP3DK111914
  • June 1, 2016 - May 31, 2021 - Functional Testing of Host Genes that control HIV Latency in Primary Immune Cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: DP2DA042423

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, 2016, 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
  • 2018
    Elected Member, American Society of Clinical Investors (ASCI)
  • 2019
    Lloyd J. Old STAR Award, Cancer Research Institute (CRI)

Selected Publications

  1. Shy BR, Vykunta VS, Ha A, Talbot A, Roth TL, Nguyen DN, Pfeifer WG, Chen YY, Blaeschke F, Shifrut E, Vedova S, Mamedov MR, Chung JJ, Li H, Yu R, Wu D, Wolf J, Martin TG, Castro CE, Ye L, Esensten JH, Eyquem J, Marson A. High-yield genome engineering in primary cells using a hybrid ssDNA repair template and small-molecule cocktails. Nat Biotechnol. 2022 Aug 25.  View on PubMed
  2. Carnevale J, Shifrut E, Kale N, Nyberg WA, Blaeschke F, Chen YY, Li Z, Bapat SP, Diolaiti ME, O'Leary P, Vedova S, Belk J, Daniel B, Roth TL, Bachl S, Anido AA, Prinzing B, Ibañez-Vega J, Lange S, Haydar D, Luetke-Eversloh M, Born-Bony M, Hegde B, Kogan S, Feuchtinger T, Okada H, Satpathy AT, Shannon K, Gottschalk S, Eyquem J, Krenciute G, Ashworth A, Marson A. RASA2 ablation in T cells boosts antigen sensitivity and long-term function. Nature. 2022 Aug 24.  View on PubMed
  3. Freimer JW, Shaked O, Naqvi S, Sinnott-Armstrong N, Kathiria A, Garrido CM, Chen AF, Cortez JT, Greenleaf WJ, Pritchard JK, Marson A. Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks. Nat Genet. 2022 Jul 11.  View on PubMed
  4. Belk JA, Yao W, Ly N, Freitas KA, Chen YT, Shi Q, Valencia AM, Shifrut E, Kale N, Yost KE, Duffy CV, Daniel B, Hwee MA, Miao Z, Ashworth A, Mackall CL, Marson A, Carnevale J, Vardhana SA, Satpathy AT. Genome-wide CRISPR screens of T cell exhaustion identify chromatin remodeling factors that limit T cell persistence. Cancer Cell. 2022 07 11; 40(7):768-786.e7.  View on PubMed
  5. Johnson JR, Crosby DC, Hultquist JF, Kurland AP, Adhikary P, Li D, Marlett J, Swann J, Hüttenhain R, Verschueren E, Johnson TL, Newton BW, Shales M, Simon VA, Beltrao P, Frankel AD, Marson A, Cox JS, Fregoso OI, Young JAT, Krogan NJ. Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling. Cell Rep. 2022 04 12; 39(2):110690.  View on PubMed
  6. Hiatt J, Hultquist JF, McGregor MJ, Bouhaddou M, Leenay RT, Simons LM, Young JM, Haas P, Roth TL, Tobin V, Wojcechowskyj JA, Woo JM, Rathore U, Cavero DA, Shifrut E, Nguyen TT, Haas KM, Malik HS, Doudna JA, May AP, Marson A, Krogan NJ. A functional map of HIV-host interactions in primary human T cells. Nat Commun. 2022 04 01; 13(1):1752.  View on PubMed
  7. 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. Obesity alters pathology and treatment response in inflammatory disease. Nature. 2022 04; 604(7905):337-342.  View on PubMed
  8. Rusu I, Mennillo E, Bain JL, Li Z, Sun X, Ly KM, Rosli YY, Naser M, Wang Z, Advincula R, Achacoso P, Shao L, Razani B, Klein OD, Marson A, Turnbaugh JA, Turnbaugh PJ, Malynn BA, Ma A, Kattah MG. Microbial signals, MyD88, and lymphotoxin drive TNF-independent intestinal epithelial tissue damage. J Clin Invest. 2022 03 01; 132(5).  View on PubMed
  9. Byrnes JR, Weeks AM, Shifrut E, Carnevale J, Kirkemo L, Ashworth A, Marson A, Wells JA. Hypoxia Is a Dominant Remodeler of the Effector T Cell Surface Proteome Relative to Activation and Regulatory T Cell Suppression. Mol Cell Proteomics. 2022 04; 21(4):100217.  View on PubMed
  10. Lin-Shiao E, Pfeifer WG, Shy BR, Saffari Doost M, Chen E, Vykunta VS, Hamilton JR, Stahl EC, Lopez DM, Sandoval Espinoza CR, Deyanov AE, Lew RJ, Poirer MG, Marson A, Castro CE, Doudna JA. CRISPR-Cas9-mediated nuclear transport and genomic integration of nanostructured genes in human primary cells. Nucleic Acids Res. 2022 02 22; 50(3):1256-1268.  View on PubMed
  11. Liu D, Duan L, Rodda LB, Lu E, Xu Y, An J, Qiu L, Liu F, Looney MR, Yang Z, Allen CDC, Li Z, Marson A, Cyster JG. CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells. Science. 2022 02 11; 375(6581):eabi5965.  View on PubMed
  12. Schmidt R, Steinhart Z, Layeghi M, Freimer JW, Bueno R, Nguyen VQ, Blaeschke F, Ye CJ, Marson A. CRISPR activation and interference screens decode stimulation responses in primary human T cells. Science. 2022 02 04; 375(6580):eabj4008.  View on PubMed
  13. Sin JH, Kashyap S, Acenas D, Cortez JT, Lee J, Marson A, Matloubian M, Waterfield MR. ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8+ T Cell Effector and Memory Responses. J Immunol. 2022 03 01; 208(5):1155-1169.  View on PubMed
  14. De Silva D, Ferguson L, Chin GH, Smith BE, Apathy RA, Roth TL, Blaeschke F, Kudla M, Marson A, Ingolia NT, Cate JH. Robust T cell activation requires an eIF3-driven burst in T cell receptor translation. Elife. 2021 12 31; 10.  View on PubMed
  15. Baglaenko Y, Macfarlane D, Marson A, Nigrovic PA, Raychaudhuri S. Genome editing to define the function of risk loci and variants in rheumatic disease. Nat Rev Rheumatol. 2021 08; 17(8):462-474.  View on PubMed
  16. Gallman AE, Wolfreys FD, Nguyen DN, Sandy M, Xu Y, An J, Li Z, Marson A, Lu E, Cyster JG. Abcc1 and Ggt5 support lymphocyte guidance through export and catabolism of S-geranylgeranyl-l-glutathione. Sci Immunol. 2021 06 04; 6(60).  View on PubMed
  17. Hamilton JR, Tsuchida CA, Nguyen DN, Shy BR, McGarrigle ER, Sandoval Espinoza CR, Carr D, Blaeschke F, Marson A, Doudna JA. Targeted delivery of CRISPR-Cas9 and transgenes enables complex immune cell engineering. Cell Rep. 2021 06 01; 35(9):109207.  View on PubMed
  18. Hiatt J, Cavero DA, McGregor MJ, Zheng W, Budzik JM, Roth TL, Haas KM, Wu D, Rathore U, Meyer-Franke A, Bouzidi MS, Shifrut E, Lee Y, Kumar VE, Dang EV, Gordon DE, Wojcechowskyj JA, Hultquist JF, Fontaine KA, Pillai SK, Cox JS, Ernst JD, Krogan NJ, Marson A. Efficient generation of isogenic primary human myeloid cells using CRISPR-Cas9 ribonucleoproteins. Cell Rep. 2021 05 11; 35(6):109105.  View on PubMed
  19. Lee Y, Bogdanoff D, Wang Y, Hartoularos GC, Woo JM, Mowery CT, Nisonoff HM, Lee DS, Sun Y, Lee J, Mehdizadeh S, Cantlon J, Shifrut E, Ngyuen DN, Roth TL, Song YS, Marson A, Chow ED, Ye CJ. XYZeq: Spatially resolved single-cell RNA sequencing reveals expression heterogeneity in the tumor microenvironment. Sci Adv. 2021 04; 7(17).  View on PubMed
  20. Muller YD, Nguyen DP, Ferreira LMR, Ho P, Raffin C, Valencia RVB, Congrave-Wilson Z, Roth TL, Eyquem J, Van Gool F, Marson A, Perez L, Wells JA, Bluestone JA, Tang Q. The CD28-Transmembrane Domain Mediates Chimeric Antigen Receptor Heterodimerization With CD28. Front Immunol. 2021; 12:639818.  View on PubMed

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