Jerry Zak
Assistant Professor of Radiation Oncology and Adjunct Assistant Professor of Oncological Sciences and of Hematology
Cancer immunology, immunotherapy, reverse translation, myeloid cells, cytokines, JAK-STAT, RNA-sequencing, computational biology
Molecular Biology Program
Education
B.A. St Catharine’s College, University of Cambridge
D.Phil. University of Oxford
Ph.D. The Scripps Research Institute
Research
The Zak lab is interested in understanding the mechanisms of an effective immune response to cancer and addressing the major need of treating the >80% of cancer patients who do not respond or develop a resistance to immunotherapy. The underlying hypothesis of the research program is that myeloid cells need to be programmed into an immune-enhancing state to achieve durable responses in all patients treated with immunotherapy. We use a combination of experimental models, computational methods and studies of cancer patients to understand which pathways are required for an effective antitumor immune response and which pathways mediate immune suppression and treatment resistance. Recently, we demonstrated that JAK inhibitors are effective in combination with anti-PD1 checkpoint inhibitor in patients with lymphoma who did not respond to or relapsed after anti-PD1 monotherapy. The efficacy of this combination relies on the reprogramming of monocytes and neutrophils from an immune suppressive into a T cell-activating state. Currently, we are extending this combination to solid tumors, and the lab is exploring additional pathways to target myeloid cell plasticity including therapeutic targeting of these pathways with small molecules, antibodies and radiation therapy. We have active collaborations with medical and radiation oncologists on investigator-initiated trials with the ultimate goal of optimizing myeloid/T cell antitumor responses in all patients treated with immunotherapy.
References
- Zak, J.*; Newman, I.*; Montiel Garcia, D. J.; Parisi, D.; Head, S. R.; Ducom, J.-C.; Natarajan, P.; Cui, H.; Ul-Hasan, S. Catalyzing computational biology research at an academic research institute through an interest network. PLoS Comput. Biol. 21 (9), 2025
- Hou, Y.*; Zak, J.*, Shi, Y.; Pratumchai, I.; Dinner, B.; Wang, W.; Qin, K.; Weber, E. W.; Teijaro, J. R. & Wu, P. Transient EZH2 suppression by tazemetostat during in vitro expansion maintains T cell stemness and improves adoptive T cell therapy. Cancer Immunol. Res. 13 (1), 2025
- Zak J.*; Pratumchai, I.*; Marro, B. S.*; Marquardt, K. L.; Beheshti Zavareh, R.; Lairson, L. L.; Oldstone, M. B. A.; Varner, J. A.; Hegerova, L.; Cao, Q.; Farooq, U.; Kenkre, V. P.; Bachanova; V., Teijaro, J. R. JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma. Science, 384 (6702), 2024
- Yang, Z.; Hou, Y.; Grande, G.; Wang, C.; Shi, Y.; Zak, J.; Cho, J. H.; Liu, D.; Teijaro, J. R.; Lerner, R. A. & Wu, P. Targeted desialylation and cytolysis of tumour cells by fusing a sialidase to a bispecific T-cell engager. Nat. Biomed. Eng. 8, p. 499–512, 2024
- Pratumchai, I.; Zak, J.; Huang, Z.; Min, B.; Oldstone, M. B. A. & Teijaro, J. R. B cell-derived IL-27 promotes clearance of persistent LCMV infection Proc. Natl. Acad. Sci. USA 119 (3), 2022
- Huang, Z.*; Kang, S. G.*; Li, Y.*; Zak, J.; Shaabani, N.; Deng, K.; Shepherd, J.; Bhargava, R.; Teijaro, J. R. & Xiao, C. IFNAR1 Signaling in NK Cells Promotes Persistent Virus Infection. Sci. Adv. 7 (13), 2021
- Marro, B. S.*; Zak, J.*; Zavareh, R. B.; Teijaro, J. R.; Lairson, L. L. & Oldstone, M. B. A. Discovery of small molecules for the reversal of T cell exhaustion. Cell Rep. 29 (10), 2019
- Huang, Z.*; Zak, J.*; Pratumchai, I.*; Shaabani, N.; Vartabedian, V. F.; Nguyen, N.; Wu, T.; Xiao, C. and Teijaro, J. R. IL-27 promotes the expansion of self-renewing CD8+ T cells in persistent viral infection J. Exp. Med., 216 (8), 2019
- Zak, J.; Schuster-Boeckler, B.; Bond, G. Cancer Genetics May Aid Diagnostics of Developmental Disorders. Human Mutat. 37, 2016
- Zak, J.; Vives, V.; Szumska, D.; Miller, P.; Vernet, A.; Schneider, J. E.; Slee, E.; Joss, S.; Lacassie, Y.; Chen, E.; Escobar, L.; Tucker, M.; Aylsworth, A.; Dubbs, H.; Collins, T. A.; Andrieux, J.; Dieux-Coeslier, A.; Aubell, K.; Haberlandt, E.; Kotzot, D.; Scott, D. A.; Parker, M. J.; Zakaria, Z.; Choy, Y. S.; Wieczorek, D.; Innes, A. M.; Ran-Jun, K.; Zinner, S.; Prin, F.; Pretorius, P.; Rosenfeld, J. A.; Mohun, T. J. and Lu, X. ASPP2 deficiency causes features of the 1q41q42 microdeletion syndrome. Cell Death Differ., 23 (12), 2016
- Zak, J. and Lu, X. Aspp1: A Guardian of Hematopoietic Stem Cell Integrity. Cell Stem Cell, 17 (1), 2015
- Lu, M.; Zak, J.; Chen, S.; Pulido, L. S.; Severson, D. T.; Endicott, J.; Ponting, C. P.; Schofield, C. J.; Lu, X. A code for RanGDP binding in ankyrin repeats defines a nuclear import pathway. Cell, 157 (5), 2014