Tomasz Zal, Ph.D.
Department of Leukemia, Division of Cancer Medicine
About Dr. Zal
Dr. Tomasz Zal is an Associate Professor in the Department of Immunology and the Scientific Director of the Advanced Microscopy Core Facility. His research focuses on the regulation of T cell activation and the dynamics of T cell – host –cancer interactions. Dr. Zal has a strong background in molecular immunology and biophysics which is conducive for interdisciplinary research projects leveraging advanced imaging technologies in basic immunology. His prior work delineated the central and peripheral mechanisms of T cell tolerance to soluble self-antigen, demonstrated the role of dual T cell Receptor (TCR) expression in the central tolerance escape, and uncovered how mature T cell activation is regulated by the spatiotemporal interactions between TCR and CD4 or CD8 coreceptors in the immunological synapse. Since joining MD Anderson Cancer Center, he has developed a research program in cancer immunology aiming to better understand how the adaptive immune surveillance is regulated by the tissue microenvironment of organs and tumors. Using intravital 2-photon (multiphoton) microscopy, phosphorescence lifetime imaging microscopy (PLIM) and multi-color lineage reporter mouse models, studies in his lab are uncovering the regulatory role of organ tissue in tumor immune surveillance, such as by the myeloid compartment, chemokines and tumor hypoxia in diverse types of tumors including lung, brain and hematological malignancies. Enjoying teaching, he is adjunct faculty for the MD Anderson Cancer Center UTHealth Graduate School of Biological Sciences (GSBS), where he lectures in the Core Course and basic and advanced immunology and mentors both graduate students and postdocs. He has developed the Advanced Microscopy Core Facility to include S10-funded Super-Resolution Structured Illumination and Single Molecule Localization Microscopes, live cell confocal, and advanced image analysis in the MD Anderson South Campus.
Present Title & Affiliation
Dual/Joint/Adjunct Appointment
Associate Professor, Department of Molecular and Cellular Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Research Interests
Our laboratory is interested in tissue regulation of immunity, which we investigate by combining various immunological and genetic techniques with dynamic visualization such as by intravital multiphoton, confocal, FRET and super-resolution fluorescence microscopy.
The immune system can recognize cancerous cells in vivo, and tumor antigen-recognizing cytotoxic lymphocytes can exterminate such cells in vitro, but the in vivo anti-tumor immune responses are subdued by the hostile tumor microenvironment. Exactly how lymphocytes are affected by the tumor microenvironment is of primary interest for the design and optimization of anti-tumor immunotherapies. To better understand the spatiotemporal regulation of immune cells inside tumors, we use intravital microscopy and a variety of agents, including nanomaterials in various tumor models in mice. By this approach, we can visualize and quantify the dynamics of specific cell populations and signaling pathways at a single cell- and subcellular-resolution in the context of tissue in vivo. We find in lung metastases that the recruitment and activity of tumor-infiltrating lymphocytes critically depends on tumor-associated CD11c + dendritic cells (DCs) and that these DCs can both promote and downregulate anti-tumor immune responses. Thus on the one hand, tumor-associated DCs can probe the cytoplasm of cancer cells, thereby initiating tumor antigen cross-presentation, but on the other hand this complex cell population recruits and interacts with the FoxP3+ Treg cells - an immune-suppressory T cell subpopulation. Currently, our goal is to understand how the interactions between tumor cells, DCs, Treg cells and other tumor-infiltrating lymphocytes are regulated in vivo with the hope that these interactions can be targeted for anti-tumor immunotherapy.
T cells recognize antigens through the T cell antigen receptor (TCR), whose composition divides all T cells into the alpha/beta and gamma/delta lineages. Unlike alpha/beta T cells which circulate through lymphoid organs, gamma/delta T cells reside primarily in environment-exposed bodily epithelia, such as in the intestine, reproductive organs, lungs, and in mice, the epidermis, where they are involved in tissue surveillance and homeostatic functions. Both alpha/beta and gamma/delta T cell lineages can become cytotoxic toward tumors and without them cancers progress rapidly. It is well established that most alpha/beta TCRs recognize MHC-associated non-self peptides, which can arise due to infection or mutations, such as cancer-driving mutations, but the biological role of gamma/delta TCRs is less clear. Using intravital and in situ microscopy in mice, we discovered that the epidermal gamma/delta T cells use their canonical Vg5 TCR to engage in a steady-state activatory interaction with the healthy epidermis, resulting in the formation of synapse-like phosphotyrosine-rich assemblies located on projections (PALPs) near the apical barrier-forming squamous keratinocyte tight junctions, including in germ-free mice. Our results indicate that intraepithelial gamma/delta TCRs may recognize distinctly localized epithelial self-ligands. We hope to leverage the intravital visualization approach to understand how this and other receptor-ligand interactions contribute to the anti-tumor and homeostatic functionalities of gamma/delta T cells.
Education & Training
Degree-Granting Education
| 1992 | Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, POL, PhD, Molecular Biology |
| 1988 | Wroclaw University of Technology, Wroclaw, POL, MSc, Biochemistry, Microbiology |
Postgraduate Training
| 1997-2001 | Postdoctoral Fellowship, Immunology, The Scripps Research Institute, La Jolla, CA |
| 1992-1997 | Postdoctoral Fellowship, Immunology, National Institute for Medical Research (NIMR), London |
Experience & Service
Academic Appointments
Assistant Professor, Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2004 - 2012
Institutional Committee Activities
Member, Institutional Animal Care and Use Committee (IACUC), 2009 - 2014
Selected Publications
Peer-Reviewed Articles
- Rytelewski M, Haryutyunan K, Nwajei F, Shanmugasundaram M, Wspanialy P, Zal MA, Chen CH, El Khatib M, Plunkett S, Vinogradov SA, Konopleva M, Zal T. Merger of dynamic two-photon and phosphorescence lifetime microscopy reveals dependence of lymphocyte motility on oxygen in solid and hematological tumors. J Immunother Cancer 7(1):78, 2019. e-Pub 2019. PMID: 30885258.
- Jayaprakash P, Ai M, Liu A, Budhani P, Bartkowiak T, Sheng J, Ager C, Nicholas C, Jaiswal AR, Sun Y, Shah K, Balasubramanyam S, Li N, Wang G, Ning J, Zal A, Zal T, Curran MA. Targeted hypoxia reduction restores T cell infiltration and sensitizes prostate cancer to immunotherapy. J Clin Invest 128(11):5137-5149, 2018. e-Pub 2018. PMID: 30188869.
- Gabrusiewicz K, Li X, Wei J, Hashimoto Y, Marisetty AL, Ott M, Wang F, Hawke D, Yu J, Healy LM, Hossain A, Akers JC, Maiti SN, Yamashita S, Shimizu Y, Dunner K, Zal MA, Burks JK, Gumin J, Nwajei F, Rezavanian A, Zhou S, Rao G, Sawaya R, Fuller GN, Huse JT, Antel JP, Li S, Cooper L, Sulman EP, Chen C, Geula C, Kalluri R, Zal T, Heimberger AB. Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1 expression on human monocytes. Oncoimmunology 7(4):e1412909, 2018. e-Pub 2018. PMID: 29632728.
- Chodaczek G, Toporkiewicz M, Zal MA, Zal T. Epidermal T Cell Dendrites Serve as Conduits for Bidirectional Trafficking of Granular Cargo. Front Immunol 9:1430, 2018. e-Pub 2018. PMID: 29988392.
- Havranek O, Xu J, Köhrer S, Wang Z, Becker L, Comer JM, Henderson J, Ma W, Man Chun Ma J, Westin JR, Ghosh D, Shinners N, Sun L, Yi AF, Karri AR, Burger JA, Zal T, Davis RE. Tonic B-cell receptor signaling in diffuse large B-cell lymphoma. Blood 130(8):995-1006, 2017. e-Pub 2017. PMID: 28646116.
- Tan X, Banerjee P, Guo HF, Ireland S, Pankova D, Ahn YH, Nikolaidis IM, Liu X, Zhao Y, Xue Y, Burns AR, Roybal J, Gibbons DL, Zal T, Creighton CJ, Ungar D, Wang Y, Kurie JM. Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11. J Clin Invest 127(1):117-131, 2017. e-Pub 2016. PMID: 27869652.
- Chen Y, Terajima M, Yang Y, Sun L, Ahn YH, Pankova D, Puperi DS, Watanabe T, Kim MP, Blackmon SH, Rodriguez J, Liu H, Behrens C, Wistuba II, Minelli R, Scott KL, Sanchez-Adams J, Guilak F, Pati D, Thilaganathan N, Burns AR, Creighton CJ, Martinez ED, Zal T, Grande-Allen KJ, Yamauchi M, Kurie JM. Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma. J Clin Invest 125(3):1147-62, 2015. e-Pub 2015. PMID: 25664850.
- Yu J, Zhou X, Chang M, Nakaya M, Chang JH, Xiao Y, Lindsey JW, Dorta-Estremera S, Cao W, Zal A, Zal T, Sun SC. Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation. Nat Commun 6:6074, 2015. e-Pub 2015. PMID: 25606824.
- Schietinger A, Arina A, Liu RB, Wells S, Huang J, Engels B, Bindokas V, Bartkowiak T, Lee D, Herrmann A, Piston DW, Pittet MJ, Lin PC, Zal T, Schreiber H. Longitudinal confocal microscopy imaging of solid tumor destruction following adoptive T cell transfer. Oncoimmunology 2(11):e26677, 2013. e-Pub 2013. PMID: 24482750.
- Hu H, Brittain GC, Chang JH, Puebla-Osorio N, Jin J, Zal A, Xiao Y, Cheng X, Chang M, Fu YX, Zal T, Zhu C, Sun SC. OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3. Nature 494(7437):371-4, 2013. e-Pub 2013. PMID: 23334419.
- Bhatnagar P, Li Z, Choi Y, Guo J, Li F, Lee DY, Figliola M, Huls H, Lee DA, Zal T, Li KC, Cooper LJ. Imaging of genetically engineered T cells by PET using gold nanoparticles complexed to Copper-64. Integr Biol (Camb) 5(1):231-8, 2013. PMID: 23034721.
- Nevozhay D, Zal T, Balázsi G. Transferring a synthetic gene circuit from yeast to mammalian cells. Nat Commun 4:1451, 2013. PMID: 23385595.
- Ariotti S, Beltman JB, Chodaczek G, Hoekstra ME, van Beek AE, Gomez-Eerland R, Ritsma L, van Rheenen J, Marée AF, Zal T, de Boer RJ, Haanen JB, Schumacher TN. Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen. Proc Natl Acad Sci U S A 109(48):19739-44, 2012. e-Pub 2012. PMID: 23150545.
- Talukder AH, Bao M, Kim TW, Facchinetti V, Hanabuchi S, Bover L, Zal T, Liu YJ. Phospholipid scramblase 1 regulates Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells. Cell Res 22(7):1129-39, 2012. e-Pub 2012. PMID: 22453241.
- Chodaczek G, Papanna V, Zal MA, Zal T. Body-barrier surveillance by epidermal γδ TCRs. Nat Immunol 13(3):272-82, 2012. e-Pub 2012. PMID: 22327568.
- Hirve N, Levytskyy RM, Rigaud S, Guimond DM, Zal T, Sauer K, Tsoukas CD. A conserved motif in the ITK PH-domain is required for phosphoinositide binding and TCR signaling but dispensable for adaptor protein interactions. PLoS One 7(9):e45158, 2012. e-Pub 2012. PMID: 23028816.
- Zal T. Visualization of Protein Interactions in Living Cells. Self Nonself 2(2):98-107, 2011. e-Pub 2011. PMID: 22299061.
- Rostro-Kohanloo BC, Bickford LR, Payne CM, Day ES, Anderson LJ, Zhong M, Lee S, Mayer KM, Zal T, Adam L, Dinney CP, Drezek RA, West JL, Hafner JH. The stabilization and targeting of surfactant-synthesized gold nanorods. Nanotechnology 20(43):434005, 2009. e-Pub 2009. PMID: 19801751.
- Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, Homey B, Barrat FJ, Zal T, Gilliet M. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med 206(9):1983-94, 2009. e-Pub 2009. PMID: 19703986.
- Ma LJ, Acero LF, Zal T, Schluns KS. Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8alphaalpha IELs. J Immunol 183(2):1044-54, 2009. e-Pub 2009. PMID: 19553528.
- Chamilos G, Lewis RE, Hu J, Xiao L, Zal T, Gilliet M, Halder G, Kontoyiannis DP. Drosophila melanogaster as a model host to dissect the immunopathogenesis of zygomycosis. Proc Natl Acad Sci U S A 105(27):9367-72, 2008. e-Pub 2008. PMID: 18583479.
- Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Wang YH, Su B, Nestle FO, Zal T, Mellman I, Schröder JM, Liu YJ, Gilliet M. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449(7162):564-9, 2007. e-Pub 2007. PMID: 17873860.
- Zal T, Zal MA, Lotz C, Goergen CJ, Gascoigne NR. Spectral shift of fluorescent dye FM4-64 reveals distinct microenvironment of nuclear envelope in living cells. Traffic 7(12):1607-13, 2006. e-Pub 2006. PMID: 17052249.
- Zambricki E, Zal T, Yachi P, Shigeoka A, Sprent J, Gascoigne N, McKay D. In vivo anergized T cells form altered immunological synapses in vitro. Am J Transplant 6(11):2572-9, 2006. e-Pub 2006. PMID: 16952297.
- Yachi PP, Ampudia J, Zal T, Gascoigne NR. Altered peptide ligands induce delayed CD8-T cell receptor interaction--a role for CD8 in distinguishing antigen quality. Immunity 25(2):203-11, 2006. e-Pub 2006. PMID: 16872849.
- Wirz SA, Davis CN, Lu X, Zal T, Bartfai T. Homodimerization and internalization of galanin type 1 receptor in living CHO cells. Neuropeptides 39(6):535-46, 2005. e-Pub 2005. PMID: 16242774.
- Yachi PP, Ampudia J, Gascoigne NR, Zal T. Nonstimulatory peptides contribute to antigen-induced CD8-T cell receptor interaction at the immunological synapse. Nat Immunol 6(8):785-92, 2005. e-Pub 2005. PMID: 15980863.
- Lin MY, Zal T, Ch'en IL, Gascoigne NR, Hedrick SM. A pivotal role for the multifunctional calcium/calmodulin-dependent protein kinase II in T cells: from activation to unresponsiveness. J Immunol 174(9):5583-92, 2005. PMID: 15843557.
- Zal T, Gascoigne NR. Photobleaching-corrected FRET efficiency imaging of live cells. Biophys J 86(6):3923-39, 2004. PMID: 15189889.
- Zal T, Zal MA, Gascoigne NR. Inhibition of T cell receptor-coreceptor interactions by antagonist ligands visualized by live FRET imaging of the T-hybridoma immunological synapse. Immunity 16(4):521-34, 2002. PMID: 11970876.
- Zal T, Weiss S, Mellor A, Stockinger B. Expression of a second receptor rescues self-specific T cells from thymic deletion and allows activation of autoreactive effector function. Proc Natl Acad Sci U S A 93(17):9102-7, 1996. PMID: 8799161.