Zachary Steinhart, PhD
Assistant Professor
Otolaryngology
School of Medicine

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.

• Bidirectional epigenetic editing reveals hierarchies in gene regulation.
  Nature biotechnology 2024 Pacalin NM, Steinhart Z, Shi Q, Belk JA, Dorovskyi D, Kraft K, Parker KR, Shy BR, Marson A, Chang HY
• An evolved AAV variant enables efficient genetic engineering of murine T cells.
  Cell 2023 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
• SCFFBXW7 regulates G2-M progression through control of CCNL1 ubiquitination.
  EMBO reports 2022 O'Brien S, Kelso S, Steinhart Z, Orlicky S, Mis M, Kim Y, Lin S, Sicheri F, Angers S
• CRISPR activation and interference screens decode stimulation responses in primary human T cells.
  Science (New York, N.Y.) 2022 Schmidt R, Steinhart Z, Layeghi M, Freimer JW, Bueno R, Nguyen VQ, Blaeschke F, Ye CJ, Marson A
• Evaluation of SARS-CoV-2 serology assays reveals a range of test performance.
  Nature biotechnology 2020 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 …
• Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer.
  Nature communications 2020 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, …
• Single-molecule dynamics of Dishevelled at the plasma membrane and Wnt pathway activation.
  Proceedings of the National Academy of Sciences of the United States of America 2020 Ma W, Chen M, Kang H, Steinhart Z, Angers S, He X, Kirschner MW
• Test performance evaluation of SARS-CoV-2 serological assays.
  medRxiv : the preprint server for health sciences 2020 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 …
• IPO11 mediates βcatenin nuclear import in a subset of colorectal cancers.
  The Journal of cell biology 2020 Mis M, O'Brien S, Steinhart Z, Lin S, Hart T, Moffat J, Angers S
• Tailored tetravalent antibodies potently and specifically activate Wnt/Frizzled pathways in cells, organoids and mice.
  eLife 2019 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
• Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells.
  Cell reports 2019 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
• A synthetic anti-Frizzled antibody engineered for broadened specificity exhibits enhanced anti-tumor properties.
  mAbs 2018 Pavlovic Z, Adams JJ, Blazer LL, Gakhal AK, Jarvik N, Steinhart Z, Robitaille M, Mascall K, Pan J, Angers S, Moffat J, Sidhu SS
• Wnt signaling in development and tissue homeostasis.
  Development (Cambridge, England) 2018 Steinhart Z, Angers S
• Corrigendum: Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors.
  Nature medicine 2017 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.
  Nature medicine 2016 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
• Essential role of the Dishevelled DEP domain in a Wnt-dependent human-cell-based complementation assay.
  Journal of cell science 2016 Gammons MV, Rutherford TJ, Steinhart Z, Angers S, Bienz M
• Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins.
  Proceedings of the National Academy of Sciences of the United States of America 2016 Cervenka I, Valnohova J, Bernatik O, Harnos J, Radsetoulal M, Sedova K, Hanakova K, Potesil D, Sedlackova M, Salasova A, Steinhart Z, Angers S, Schulte G, Hampl A, Zdrahal Z, Bryja V
• High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities.
  Cell 2015 Hart T, Chandrashekhar M, Aregger M, Steinhart Z, Brown KR, MacLeod G, Mis M, Zimmermann M, Fradet-Turcotte A, Sun S, Mero P, Dirks P, Sidhu S, Roth FP, Rissland OS, Durocher D, Angers S, Moffat J