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.
Associate Professor, Department of Molecular and Cellular Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
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.
|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|
|1997-2001||Postdoctoral Fellowship, Immunology, The Scripps Research Institute, La Jolla, CA|
|1992-1997||Postdoctoral Fellowship, Immunology, National Institute for Medical Research (NIMR), London|
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