Jaroslav Zak

Jaroslav Zak, DPhil, PhD

Languages spoken: English, German, Czech

Academic Information

Departments Adjunct - Oncological Sciences , Primary - Radiation Oncology , Adjunct - Internal Medicine

Divisions: Hematology & Hematologic Malignancies

A cancer immunologist interested in mechanisms of response vs resistance to cancer immunotherapy and developing myeloid cell-targeting therapies.

Research Statement

Dr Zak is a cancer immunologist interested in enhancing the immune response to cancer and combating resistance to current immunotherapies. Using experimental model systems, computational and clinical research approaches, the Zak lab investigates fundamental mechanisms of the immune response to cancer and identifies druggable pathways of immune suppression. For example, Dr Zak identified JAK inhibitors in combination with anti-PD1 as a promising combination immunotherapy that reprograms immune suppressive into immune-enhancing myeloid cells. In collaboration with clinical oncologists on an investigator-initiated clinical trial, this combination therapy showed promising efficacy in patients with lymphoma who did not respond to or relapsed after previous anti-PD1 therapy. The lab is currently exploring additional myeloid-modulating strategies in clinical trials of lymphoma and solid tumors and aims to investigate the molecular mechanisms that maximize the anti-tumor functional state of T and myeloid cells.

Education History

Undergraduate St Catharine¿s College, University of Cambridge
 BA
Graduate Training St Catharine¿s College, University of Cambridge
 MSci
Doctoral Training University of Oxford
 DPhil
Doctoral Training Scripps Research
 PhD
Graduate Training St Catharine¿s College, University of Cambridge
 MA
Postdoctoral Training Scripps Research
 Postdoctoral Associate
Postdoctoral Fellowship Scripps Research, Cancer Research Institute (CRI) Irvington
 Postdoctoral Fellow

Selected Publications

Journal Article

  1. Shaabani N, Zak J, Johnson JL, Huang Z, Nguyen N, Lazar DC, Vartabedian VF, Honke N, Prinz M, Knobeloch KP, Arimoto K, Zhang D, Catz SD, Teijaro J (2024). ISG15 drives immune pathology and respiratory failure during viral infection. Journal of immunology (Baltimore, Md., 213(12), 1811-1824.
  2. Shepard RM, Ghebremedhin A, Pratumchai I, Robinson SR, Betts C, Hu J, Sasik R, Fisch KM, Zak J, Chen H, Paradise M, Rivera J, Amjad M, Uchiyama S, Seo H, Campos AD, Dayao DA, Tzipori S, Piedra-Mora C, Das S, Hasteh F, Russo H, Sun X, Xu L, E Alexander LC, Duran JM, Odish M, Pretorius V, Kirchberger NC, Chin SM, Von Schalscha T, Cheresh D, Morrey JD, Alargova R, O'Connell B, Martinot TA, Patel SP, Nizet V, Martinot AJ, Coussens LM, Teijaro JR, Varner J (2024). PI3K¿ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections. Science translational medicine, 16(754), eadi6887.
  3. Zak J*, Pratumchai I*, Marro BS*, Marquardt KL, Zavareh RB, Lairson LL, Oldstone MBA, Varner JA, Hegerova L, Cao Q, Farooq U, Kenkre VP, Bachanova V, Teijaro J (2024). JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma. Science (New York, N.Y.), 384(6702), eade8520.
  4. Yang Z, Hou Y, Grande G, Cho JH, Wang C, Shi Y, Zak J, Wan Y, Qin K, Liu D, Teijaro JR, Lerner RA, Wu (2024). Targeted desialylation and cytolysis of tumour cells by fusing a sialidase to a bispecific T-cell engager. Nature biomedical engineering, 8(5), 499-512.
  5. Pagnamenta AT, Camps C, Giacopuzzi E, Taylor JM, Hashim M, Calpena E, Kaisaki PJ, Hashimoto A, Yu J, Sanders E, Schwessinger R, Hughes JR, Lunter G, Dreau H, Ferla M, Lange L, Kesim Y, Ragoussis V, Vavoulis DV, Allroggen H, Ansorge O, Babbs C, Banka S, Baños-Piñero B, Beeson D, Ben-Ami T, Bennett DL, Bento C, Blair E, Brasch-Andersen C, Bull KR, Cario H, Cilliers D, Conti V, Davies EG, Dhalla F, Dacal BD, Dong Y, Dunford JE, Guerrini R, Harris AL, Hartley J, Hollander G, Javaid K, Kane M, Kelly D, Kelly D, Knight SJL, Kreins AY, Kvikstad EM, Langman CB, Lester T, Lines KE, Lord SR, Lu X, Mansour S, Manzur A, Maroofian R, Marsden B, Mason J, McGowan SJ, Mei D, Mlcochova H, Murakami Y, Németh AH, Okoli S, Ormondroyd E, Ousager LB, Palace J, Patel SY, Pentony MM, Pugh C, Rad A, Ramesh A, Riva SG, Roberts I, Roy N, Salminen O, Schilling KD, Scott C, Sen A, Smith C, Stevenson M, Thakker RV, Twigg SRF, Uhlig HH, van Wijk R, Vona B, Wall S, Wang J, Watkins H, Zak J, Schuh AH, Kini U, Wilkie AOM, Popitsch N, Taylor J (2023). Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases. Genome medicine, 15(1), 94.
  6. Pratumchai I, Zak J, Huang Z, Min B, Oldstone MBA, Teijaro J (2022). B cell-derived IL-27 promotes control of persistent LCMV infection. Proceedings of the National Academy of Sciences of the United States of America, 119(3),
  7. Huang Z*, Kang SG*, Li Y*, Zak J, Shaabani N, Deng K, Shepherd J, Bhargava R, Teijaro JR, Xiao (2021). IFNAR1 signaling in NK cells promotes persistent virus infection. Science advances, 7(13),
  8. Marro BS*, Zak J*, Zavareh RB, Teijaro JR, Lairson LL, Oldstone MB (2019). Discovery of Small Molecules for the Reversal of T Cell Exhaustion. Cell reports, 29(10), 3293-3302.e3.
  9. Huang Z*, Zak J*, Pratumchai I*, Shaabani N, Vartabedian VF, Nguyen N, Wu T, Xiao C, Teijaro J (2019). IL-27 promotes the expansion of self-renewing CD8(+) T cells in persistent viral infection. The Journal of experimental medicine, 216(8), 1791-1808.
  10. O'Donnell-Luria AH, Pais LS, Faundes V, Wood JC, Sveden A, Luria V, Abou Jamra R, Accogli A, Amburgey K, Anderlid BM, Azzarello-Burri S, Basinger AA, Bianchini C, Bird LM, Buchert R, Carre W, Ceulemans S, Charles P, Cox H, Culliton L, Currò A, Deciphering Developmental Disorders (DDD) Study, Demurger F, Dowling JJ, Duban-Bedu B, Dubourg C, Eiset SE, Escobar LF, Ferrarini A, Haack TB, Hashim M, Heide S, Helbig KL, Helbig I, Heredia R, Héron D, Isidor B, Jonasson AR, Joset P, Keren B, Kok F, Kroes HY, Lavillaureix A, Lu X, Maas SM, Maegawa GHB, Marcelis CLM, Mark PR, Masruha MR, McLaughlin HM, McWalter K, Melchinger EU, Mercimek-Andrews S, Nava C, Pendziwiat M, Person R, Ramelli GP, Ramos LLP, Rauch A, Reavey C, Renieri A, Rieß A, Sanchez-Valle A, Sattar S, Saunders C, Schwarz N, Smol T, Srour M, Steindl K, Syrbe S, Taylor JC, Telegrafi A, Thiffault I, Trauner DA, van der Linden H Jr, van Koningsbruggen S, Villard L, Vogel I, Vogt J, Weber YG, Wentzensen IM, Widjaja E, Zak J, Baxter S, Banka S, Rodan L (2019). Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy. American journal of human genetics, 104(6), 1210-1222.
  11. Marro BS, Ware BC, Zak J, de la Torre JC, Rosen H, Oldstone M (2017). Progression of type 1 diabetes from the prediabetic stage is controlled by interferon-¿ signaling. Proceedings of the National Academy of Sciences of the United States of America, 114(14), 3708-3713.
  12. Zak J, Vives V, Szumska D, Vernet A, Schneider JE, Miller P, Slee EA, Joss S, Lacassie Y, Chen E, Escobar LF, Tucker M, Aylsworth AS, Dubbs HA, Collins AT, Andrieux J, Dieux-Coeslier A, Haberlandt E, Kotzot D, Scott DA, Parker MJ, Zakaria Z, Choy YS, Wieczorek D, Innes AM, Jun KR, Zinner S, Prin F, Lygate CA, Pretorius P, Rosenfeld JA, Mohun TJ, Lu (2016). ASPP2 deficiency causes features of 1q41q42 microdeletion syndrome. Cell death and differentiation, 23(12), 1973-1984.
  13. Royer C, Koch S, Qin X, Zak J, Buti L, Dudziec E, Zhong S, Ratnayaka I, Srinivas S, Lu (2014). ASPP2 links the apical lateral polarity complex to the regulation of YAP activity in epithelial cells. PloS one, 9(10), e111384.
  14. Wang Y, Bu F, Royer C, Serres S, Larkin JR, Soto MS, Sibson NR, Salter V, Fritzsche F, Turnquist C, Koch S, Zak J, Zhong S, Wu G, Liang A, Olofsen PA, Moch H, Hancock DC, Downward J, Goldin RD, Zhao J, Tong X, Guo Y, Lu (2014). ASPP2 controls epithelial plasticity and inhibits metastasis through ß-catenin-dependent regulation of ZEB1. Nature cell biology, 16(11), 1092-104.
  15. Lu M, Zak J, Chen S, Sanchez-Pulido L, Severson DT, Endicott J, Ponting CP, Schofield CJ, Lu (2014). A code for RanGDP binding in ankyrin repeats defines a nuclear import pathway. Cell, 157(5), 1130-45.
  16. Koblizek V, Chlumsky J, Zindr V, Neumannova K, Zatloukal J, Zak J, Sedlak V, Kocianova J, Zatloukal J, Hejduk K, Pracharova S, Czech Pneumological and Phthisiological Societ (2013). Chronic Obstructive Pulmonary Disease: official diagnosis and treatment guidelines of the Czech Pneumological and Phthisiological Society; a novel phenotypic approach to COPD with patient-oriented care. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia, 157(2), 189-201.
  17. Zak J, Ron D, Riva E, Harding HP, Cross BC, Baxendale I (2012). Establishing a flow process to coumarin-8-carbaldehydes as important synthetic scaffolds. Chemistry'A European Journal, 18(32), 9901-10.
  18. Cross BC, Bond PJ, Sadowski PG, Jha BK, Zak J, Goodman JM, Silverman RH, Neubert TA, Baxendale IR, Ron D, Harding H (2012). The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proceedings of the National Academy of Sciences of the United States of America, 109(15), E869-78.
  19. Zak J, Lu (2015). Aspp1: A Guardian of Hematopoietic Stem Cell Integrity. Cell stem cell, 17(1), 3-5.
  20. Hou Y*, Zak J*, Shi Y, Pratumchai I, Dinner B, Wang W, Qin K, Weber EW, Teijaro JR, Wu (2024). Transient EZH2 suppression by tazemetostat during in vitro expansion maintains T cell stemness and improves adoptive T cell therapy. Cancer immunology research,
  21. Zak J, Newman I, Montiel Garcia DJ, Parisi D, Joy J, Head SR, Ducom JC, Natarajan P, Cui H, Ul-Hasan (2025). Catalyzing computational biology research at an academic institute through an interest network. PLoS computational biology, 21(9), e1013453.

Review

  1. Zak J, Varner J (2025). Positive and negative roles of myeloid cells in cancer immunotherapy. Journal for immunotherapy of cancer, 13(10),
  2. Zak J, Teijaro J (2026). Beyond suppression: the paradox of JAK inhibitors as amplifiers of cancer immunotherapy. Nature reviews. Immunology,

Editorial

  1. Zak J, Schuster-Boeckler B, Bond (2016). Cancer Genetics May Aid Diagnostics of Developmental Disorders. Human mutation, 37(10), 989.