Research Summary

The Steinhart Lab aims to apply CRISPR-based functional genomics and gene editing approaches to understand and engineer antitumor immunity. We are particularly interested in studying the genetic basis of signaling, receiving, and processing in the communication networks between tumor, tumor-associated cells, and antitumor T cells in solid tumor microenvironments. We are developing new technologies to rapidly uncover and study the genes controlling these networks using combinatorial gene perturbation approaches coupled with advanced phenotypic readouts. Importantly, we aim to apply these tools in the most disease and therapeutically relevant human cell types, including primary human T cells, and patient-derived tumor infiltrating lymphocytes (TILs) and tumor cells. Our end goal is to translate discoveries to next-generation adoptive cell therapies and/or leverage druggable target discovery to develop novel therapies to enhance antitumor immunity.

Education

  • Queens University, Kingston, Ontario, Canada, BS, 2012, Life Sciences
  • University of Toronto, PhD, 2019, Pharmaceutical Sciences
  • Gladstone Institutes, San Francisco, Postdoctoral, 2024, Genomic Immunology  

Honors & Awards

  • 2024
    Gladstone Institutes Distinguished Achievement in Science Award
  • 2024
    Parker Institute for Cancer Immunotherapy Bridge Fellowship Award
  • 2021
    Gladstone Institutes Distinguished Achievement in Science Award
  • 2021
    Parker Institute for Cancer Immunotherapy Parker Scholars Award
  • 2018
    ASBMB graduate travel award for ASBMB annual meeting
  • 2016
    Centre for Pharmaceutical Oncology Graduate Scholarship – University of Toronto

Selected Publications

  1. Jung H, Devant P, Ching C, Ota M, Hamilton J, Steinhart Z, Ngo W, Sandoval L, Jung JH, Xu D, An M, Urs E, Chen PA, Allain V, Tada T, Nuñez JK, Landau NR, Liu DR, Eyquem J, Doudna JA, Marson A, Carnevale J. Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells. bioRxiv. 2025 Dec 14. View on PubMed
  2. Vanderperre B, Muraleedharan A, Dorion MF, Larroquette F, Del Cid Pellitero E, Rajakulendran N, Chen CX, Larivière R, Michaud-Tardif C, Goiran T, Chidiac R, Lipuma D, MacLeod G, Thomas R, Wang Z, Reintsch WE, Luo W, Shlaifer I, Zhang F, Xia K, Steinhart Z, Linhardt RJ, Trempe JF, Liu J, Durcan TM, Angers S, Fon EA. Novel regulators of heparan sulfate proteoglycans modulate cellular uptake of α-synuclein fibrils. Commun Biol. 2025 Oct 06; 8(1):1426. View on PubMed
  3. Arce MM, Umhoefer JM, Arang N, Kasinathan S, Freimer JW, Steinhart Z, Shen H, Pham MTN, Ota M, Wadhera A, Dajani R, Dorovskyi D, Chen YY, Liu Q, Zhou Y, Swaney DL, Obernier K, Shy BR, Carnevale J, Satpathy AT, Krogan NJ, Pritchard JK, Marson A. Central control of dynamic gene circuits governs T cell rest and activation. Nature. 2025 01; 637(8047):930-939. View on PubMed
  4. Mowery CT, Freimer JW, Chen Z, Casaní-Galdón S, Umhoefer JM, Arce MM, Gjoni K, Daniel B, Sandor K, Gowen BG, Nguyen V, Simeonov DR, Garrido CM, Curie GL, Schmidt R, Steinhart Z, Satpathy AT, Pollard KS, Corn JE, Bernstein BE, Ye CJ, Marson A. Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells. Nat Genet. 2024 Jun; 56(6):1156-1167. View on PubMed
  5. Pacalin NM, Steinhart Z, Shi Q, Belk JA, Dorovskyi D, Kraft K, Parker KR, Shy BR, Marson A, Chang HY. Bidirectional epigenetic editing reveals hierarchies in gene regulation. Nat Biotechnol. 2025 Mar; 43(3):355-368. View on PubMed
  6. Nyberg WA, Ark J, To A, Clouden S, Reeder G, Muldoon JJ, Chung JY, Xie WH, Allain V, Steinhart Z, Chang C, Talbot A, Kim S, Rosales A, Havlik LP, Pimentel H, Asokan A, Eyquem J. An evolved AAV variant enables efficient genetic engineering of murine T cells. Cell. 2023 01 19; 186(2):446-460.e19. View on PubMed
  7. O'Brien S, Kelso S, Steinhart Z, Orlicky S, Mis M, Kim Y, Lin S, Sicheri F, Angers S. SCFFBXW7 regulates G2-M progression through control of CCNL1 ubiquitination. EMBO Rep. 2022 12 06; 23(12):e55044. View on PubMed
  8. 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
  9. 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 10; 38(10):1174-1183. View on PubMed
  10. Aubert L, Nandagopal N, Steinhart Z, Lavoie G, Nourreddine S, Berman J, Saba-El-Leil MK, Papadopoli D, Lin S, Hart T, Macleod G, Topisirovic I, Gaboury L, Fahrni CJ, Schramek D, Meloche S, Angers S, Roux PP. Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer. Nat Commun. 2020 07 24; 11(1):3701. View on PubMed
  11. Ma W, Chen M, Kang H, Steinhart Z, Angers S, He X, Kirschner MW. Single-molecule dynamics of Dishevelled at the plasma membrane and Wnt pathway activation. Proc Natl Acad Sci U S A. 2020 07 14; 117(28):16690-16701. View on PubMed
  12. 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. View on PubMed
  13. Mis M, O'Brien S, Steinhart Z, Lin S, Hart T, Moffat J, Angers S. IPO11 mediates βcatenin nuclear import in a subset of colorectal cancers. J Cell Biol. 2020 02 03; 219(2). View on PubMed
  14. Tao Y, Mis M, Blazer L, Ustav M, Steinhart Z, Chidiac R, Kubarakos E, O'Brien S, Wang X, Jarvik N, Patel N, Adams J, Moffat J, Angers S, Sidhu SS. Tailored tetravalent antibodies potently and specifically activate Wnt/Frizzled pathways in cells, organoids and mice. Elife. 2019 08 27; 8. View on PubMed
  15. MacLeod G, Bozek DA, Rajakulendran N, Monteiro V, Ahmadi M, Steinhart Z, Kushida MM, Yu H, Coutinho FJ, Cavalli FMG, Restall I, Hao X, Hart T, Luchman HA, Weiss S, Dirks PB, Angers S. Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells. Cell Rep. 2019 04 16; 27(3):971-986.e9. View on PubMed
  16. Pavlovic Z, Adams JJ, Blazer LL, Gakhal AK, Jarvik N, Steinhart Z, Robitaille M, Mascall K, Pan J, Angers S, Moffat J, Sidhu SS. A synthetic anti-Frizzled antibody engineered for broadened specificity exhibits enhanced anti-tumor properties. MAbs. 2018 Nov-Dec; 10(8):1157-1167. View on PubMed
  17. Steinhart Z, Angers S. Wnt signaling in development and tissue homeostasis. Development. 2018 06 08; 145(11). View on PubMed
  18. Steinhart Z, Pavlovic Z, Chandrashekhar M, Hart T, Wang X, Zhang X, Robitaille M, Brown KR, Jaksani S, Overmeer R, Boj SF, Adams J, Pan J, Clevers H, Sidhu S, Moffat J, Angers S. Corrigendum: Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors. Nat Med. 2017 Nov 07; 23(11):1384. View on PubMed
  19. Steinhart Z, Pavlovic Z, Chandrashekhar M, Hart T, Wang X, Zhang X, Robitaille M, Brown KR, Jaksani S, Overmeer R, Boj SF, Adams J, Pan J, Clevers H, Sidhu S, Moffat J, Angers S. Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors. Nat Med. 2017 01; 23(1):60-68. View on PubMed
  20. Gammons MV, Rutherford TJ, Steinhart Z, Angers S, Bienz M. Essential role of the Dishevelled DEP domain in a Wnt-dependent human-cell-based complementation assay. J Cell Sci. 2016 10 15; 129(20):3892-3902. View on PubMed

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