Dr. Ting Zhou obtained his bachelor’s degree from China Agricultural University in 2006, and his Ph.D. degree from the Institute of Biophysics, Chinese Academy of Sciences in 2014. From 2014 to 2016, he conducted his first postdoctoral training in the Department of Molecular Cellular and Developmental Biology at Yale University, studying the molecular mechanism of the highly pathogenic Hepatitis C virus (HCV-JFH1). In November 2016, he started the second postdoc training in the Department of Immunobiology at Yale School of Medicine, focusing on the biological functions of cytokines in the tumor microenvironment and synthetic engineering cytokine for next-generation cancer immunotherapy. In June 2021, he joined Westlake University as an assistant professor, studying cancer immunology and immunotherapy.

In the past few decades, the landscape of tumor immunology and immunotherapy has been reshaped, primarily attributed to two groundbreaking strides: 1) The discovery of co-stimulatory and co-inhibitory molecules, along with the successful application of immune checkpoint inhibitors like PD-1/PD-L1 antibodies in clinical; 2) The development of synthetic immunology, marked by the application of cellular therapies such as adoptive cell transfer (ACT), CAR-T, and TCR-T for specific tumor types. These macromolecule drugs and cellular therapies primarily target the major workforce of the anti-tumor immune response - T cell adaptive immunity. Their success has ushered in a new era of immunotherapy, but also given rise to two primary categories of dilemmas: 1) Immunological Concerns: Why are certain patients resistant to immune checkpoint therapy, leading to tolerance? Why is the existing T cell therapy not potent against solid tumors? 2) Pharmacological Challenges: The insights and methodologies derived from small molecule drugs don't align seamlessly with macromolecule drugs, necessitating a comprehensive reassessment.

To address the aforementioned quandaries, our laboratory has two main research directions:

From systems immunology angle, we study how adaptive cellular immunity is generated from central immune organs (such as bone marrow and thymus) to peripheral immune organs (such as spleen and lymph nodes), and then to specific tissues (such as different organs and tumors). At the same time, we study how the occurrence and development of tumors and chronic infections affect this process and escape immune surveillance and adaptive immunity.

From immuno-pharmacology angle, we study how macromolecule drug treatment regulates specific immune cell functions and the overall disturbance of the immune system. Meanwhile, we explore how pharmacological designs and treatment regimens (schedule, doses, etc) alter the immunological mechanisms. In particular, we use cytokine agonists as a model because they are not only one of the most reasonable synergistic drugs to overcome the lack of response and tolerance to immune checkpoint therapy, but also hotspot of many issues in immunopharmacology.

Our laboratory endeavors bridge the chasm between fundamental immunology and tangible clinical predicaments. The research results aim to discover new immune mechanisms while gaining a deep understanding of the pathology of clinical diseases, providing meaningful guidance for the future design and development of treatment strategies and novel drugs.

1. Zhou, T.*, Damsky, W.*, Weizman, O. E.*, McGeary, M. K., Hartmann, K. P., Rosen, C. E., Fischer, S., Jackson, R., Flavell, R. A., Wang, J., Sanmamed, M. F., Bosenberg, M. W., & Ring, A. M. (2020). IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy. Nature, 583(7817), 609–614. * Equal contribution. https://doi.org/10.1038/s41586-020-2422-6

2. Zhou, T.*, Su, T. T.*, Mudianto, T., & Wang, J. (2020). Immune asynchrony in COVID-19 pathogenesis and potential immunotherapies. The Journal ofexperimental medicine, 217(10), e20200674. * Equal contribution. https://doi.org/10.1084/jem.20200674

3. Jarret, A., Jackson, R., Duizer, C., Healy, M. E., Zhao, J., Rone, J. M., Bielecki, P., Sefik, E., Roulis, M., Rice, T., Sivanathan, K. N., Zhou, T., Solis, A. G., Honcharova-Biletska, H., Vélez, K., Hartner, S., Low, J. S., Qu, R., de Zoete, M. R., Palm, N. W., … Flavell, R. A. (2020). Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity. Cell, 180(4), 813–814. https://doi.org/10.1016/j.cell.2020.02.004

4. Wang, J., Sanmamed, M. F., Datar, I., Su, T. T., Ji, L., Sun, J., Chen, L., Chen, Y., Zhu, G., Yin, W., Zheng, L., Zhou, T., Badri, T., Yao, S., Zhu, S., Boto, A., Sznol, M., Melero, I., Vignali, D., Schalper, K., … Chen, L. (2019). Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3. Cell, 176(1-2), 334–347.e12. https://doi.org/10.1016/j.cell.2018.11.010

5. Du, W., Dong, Q., Zhang, Z., Liu, B., Zhou, T., Xu, R. M., Wang, H., Zhu, B., & Li, Y. (2019). Stella protein facilitates DNA demethylation by disrupting the chromatin association of the RING finger-type E3 ubiquitin ligase UHRF1. The Journal of biological chemistry, 294(22), 8907–8917. https://doi.org/10.1074/jbc.RA119.008008

6. Zhou, T., Ren, X., Adams, R. L., & Pyle, A. M. (2017). NS3 from Hepatitis C Virus Strain JFH-1 Is an Unusually Robust Helicase That Is Primed To Bind and Unwind Viral RNA. Journal of virology, 92(1), e01253-17. https://doi.org/10.1128/JVI.01253-17

7. Zhou, T., Xiong, J., Wang, M., Yang, N., Wong, J., Zhu, B., & Xu, R. M. (2014). Structural basis for hydroxymethylcytosine recognition by the SRA domain of UHRF2. Molecular cell, 54(5), 879–886. https://doi.org/10.1016/j.molcel.2014.04.003

E-mail: zhouting@westlake.edu.cn