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个人简介

Education Good Ventures Postdoctoral Fellowship (2015-2017) Stanford University Advisor: Carolyn R. Bertozzi Ph.D. in Chemistry (2015) The Scripps Research Institute Advisor: Peter G. Schultz B.S. in Chemistry (2010) The University of Science and Technology of China Advisor: Liu-Zhu Gong Awards and Honors Breast Cancer Research Program (BCRP) Breakthrough Award – Level 2, Department of Defense, 2021 Maximizing Investigators’ Research Award for Early Stage Investigators (MIRA), National Institute of General Medical Sciences, 2019 Hamill Innovation Award, Hamill Foundation, 2018 Norman Hackerman - Welch Young Investigator Award, 2017 CPRIT Faculty Recruitment Award, 2017 Good Ventures Postdoctoral Fellowship, 2016 Aldrich Alfred R. Bader Award for Student Innovation, 2014 Outstanding Self-Financed Students Abroad, 2013 Honors Degree in Physical Science (USTC), 2010 National Scholarship (MOE of China), 2008 Han Xiao is an Associate Professor of Chemistry, and Biosciences at Rice University. Han was born in 1986 in Changchun, Jilin, China. He obtained his undergraduate degree from the University of Science and Technology of China (USTC) where he graduated with a B.S. in chemistry and an honors degree in physical science. He conducted undergraduate research in Prof. Liu-Zhu Gong’s group, focusing on organic methodology and synthesis of natural products. After graduating from USTC in 2010, Han joined the Ph.D. program at the Scripps Research Institute (TSRI). His thesis work with Prof. Peter G. Schultz focused on expanding the technique of genetically incorporating unnatural amino acids in both prokaryotic and eukaryotic organisms and applying this technique for better cancer therapeutics. In 2015, Han joined the laboratory of Prof. Carolyn R. Bertozzi as a Good Ventures Postdoctoral Fellow of the Life Science Research Foundation at the Stanford University. In his postdoctoral work, he is engaged in the development of novel cancer immune therapy targeting the cell-surface glycans axis of immune modulation. Enzymatic precision glycocalyx editing is able to simultaneously stimulate immune-activating pathways and limit immune-inhibitory pathways within immune cells, thus leading to a promising avenue for cancer immune therapy. Currently,Han is an Associate Professor at Rice University in the Department of Chemistry. At Rice, the focus of his research is the development of various chemical biological tools allowing us to understand complex biology system as well as develop novel therapeutic strategies. His research combines elements from multiple disciplines spanning synthetic chemistry, chemical biology, molecular biology, cancer biology and immunology.

研究领域

Research Understanding complex biological systems and developing novel therapeutic approaches requires explorations at the interface of chemistry and biology. The focus of our research is the development of various chemical tools that allow us to precisely probe and manipulate biological systems. Our research combines elements from multiple disciplines spanning synthetic chemistry, chemical biology, molecular biology, cancer biology, and immunology. Precision modification of bio-molecules The ability to site-specifically introduce distinct chemical moieties (e.g. unnatural amino acid, unnatural saccharide derivatives) into biomolecules affords a powerful tool to investigate and manipulate biological systems. Here, we will expand the tool set for this purpose. We are interested in (1) adding new building blocks with novel chemical, biological, and physical properties in different biological systems; (2) enhancing the performance of chemical biological tools in various species; (3) using these tools to better understand and ultimately control various biological processes; and (4) exploring the therapeutic utilities of these tools in the context of cancer, autoimmune, and metabolic diseases. Next-generation antibody therapy Monoclonal antibodies have emerged as a successful treatment for various cancers since the 1980s. Beyond inducing tumor cell death by blocking survival pathways, their success relies substantially on their ability to coat tumor cells and promote immune cells activations against the tumor. We are actively pursuing the design and synthesis of novel antibody conjugates that enabling tumor-specific delivery of toxins as well as site-specific activation of the immune system. Advances in chemical biological tools will enable us to prepare antibody conjugates with novel scaffolds that can overcome the problems of current therapy as well as carry out novel actions. Engineering of immune cells Therapies that enhance the immune response to cancer are proving revolutionary in the fight against tumors. Chimeric antigen receptor (CAR)-engineered immune cell therapy that endows the patient’s immune cells with reactivity for tumor cell surface molecules, is emerging as an effective and innovative treatment for cancer. However, the future utility of this technology in clinical settings is greatly limited by long production times, high production costs, and complicated handling processes. We are using various chemical biological tools to engineer CAR-immune cells to overcome these limitations.

近期论文

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Wang, Y.†, Xu, Z.†, Wu, K., Yu, L., Wang, C., Ding, H., Gao, Y., Sun, H., Wu, Y., Xia, M., Chen, Y., Xiao, H. “Siglec-15/sialic acid axis as a central glyco-immune checkpoint in breast cancer bone metastasis.” Proceedings of the National Academy of Sciences (USA), 2024, DOI: 10.1073/pnas.2312929121. Cheng, L.†, Wang, Y.†, Guo, Y., Zhang, S. S., Xiao, H. “Advancing Protein Therapeutics through Proximity-Induced Chemistry.” Cell Chemical Biology, 2023, DOI: 10.1016/j.chembiol.2023.09.004. Alexander, L. T., Durairaj, J., Kryshtafovych, A., Abriata, L. A., Bayo, Y., Bhabha, G., Breyton, C., Caulton, S. G., Chen, J., Degroux, S., Ekiert, D. C., Erlandsen, B. S., Freddolino, P. L., Gilzer, D., Greening, C., Grimes, J. M., Grinter, R., Gurusaran, M., Hartmann, M. D., Hitchman, C. J., Keown, J. R., Kropp, A., Kusula, P., Lovering, A. L., Lemaitre, B., Lia, A., Liu, S., Logotheti, M., Lu, S., Markusson, S., Miller, M. D., Minasov, G., Niemann, H. H., Opazo, F., Phillips, G. N., Davies, O. R., Rommelaere, S., Rosas-Lemus, M., Roversi, P., Satchell, K., Smith, N., Wilson, M. A., Wu, K., Xia, X., Xiao, H., Zhang, W., Zhou, Z. H., Fidelis, K., Topf, M., Moult, J., Schwede, T. “Protein target highlights in CASP15: Analysis of models by structure providers.” Proteins: Structure, Function, and Bioinformatics, 2023, DOI: 10.1002/prot.26545. Yang, S., Wang, L., Loredo, A., Wang, S., Ada, N., Xiao, H. “Visible light-activated prodrug system with a novel heavy-atom-free photosensitizer.” Bioorganic & Medicinal Chemistry Letters, 2023, 91, 129365 Wang, S., Shi, H., Wang, L., Espinoza, V. B., Loredo, A., Bachilo, S. M., Tian, Z., Chen, Y., Weisman, R. B., Zhang, X., Cheng, Z., Xiao, H. “Photostable Small-Molecule NIR-II Fluorescent Scaffolds that Cross the Blood–Brain Barrier for Noninvasive Brain Imaging.” Journal of the American Chemical Society, 2022, DOI: 10.1021/jacs.2c11223. Wang, L.†, Hsiung, C. H.†, Wang, S., Loredo, A., Zhang, X., Xiao, H. “Xanthone-based solvatochromic fluorophores for quantifying micropolarity of protein aggregates.” Chemical Science, 2022, DOI: 10.1039/d2sc05004h. Chen, Y., Jin, S., Zhang, M., W, K., Chang, A., Wang, S., Tian, Z., Wolynes, P. G., Xiao, H. “Unleashing the Potential of Noncanonical Amino Acid Biosynthesis for Creation of Cells with Site-Specific Tyrosine Sulfation.” Nature Communications, 2022, DOI: 10.1038/s41467-022-33111-4. Wu, K. L., Moore, J. A., Chen, Y., Lee, C., Xu, D., Miller, M. D., Peng, Z., Duan, Q., Philips, G. N., Uribe, R. A., Xiao, H. “Expanding the Eukaryotic Genetic Code with a Biosynthesized 21st Amino Acid.” Protein Science, 2022, DOI: 10.1002/PRO.4443. Tian, Z.†, Yu, C.†, Zhang, W., Wu, K. L., Wang, C., Gupta, R., Zhan, X., Ling, W., Chen, Y., Zhang, X., Xiao, H. “Bone-Specific Enhancement of Antibody Therapy for Breast Cancer Metastasis to Bone.” ACS Central Science, 2022, DOI: 10.1021/acscentsci.1c01024. Chen, Y., Loredo, A., Chang, A., Zhang, M., Liu, R., Xiao, H. “Biosynthesis and Genetic Incorporation of L-3,4-Dihydroxyphenylalanine into Proteins.” Journal of Molecular Biology, 2021, DOI: 10.1016/j.jmb.2021.167412. Cameron, T., Vega, D., Yu, C., Xiao, H., Margolin, W. “ZipA uses a two-pronged FtsZ-binding mechanism necessary for cell division.” mBio, 2021, DOI: 10.1128/mbio.02529-21. Wang, L.†, Wang, S.†, Tang, J., Espinoza, V. B, Loredo, A., Tian, Z., Weisman, R. B., Xiao, H. “Oxime as a General Photocage for the Design of Visible Light Photoactivatable Fluorophores.” Chemical Science, 2021, DOI: 10.1039/D1SC05351E. Adeniji, O. S., Kuri-Cervantes, L., Yu, C., Xu, Z., Ho, M., Chew, G. M., Shikuma, C., Tomescu, C., George, A. F., Roan, N. R., Ndhlovu, L. C., Muthumani, K., Weiner, D. B., Xiao, H., Abdel-Mohsen, M. “Siglec-9 Defines and Restrains a Natural Killer Subpopulation Highly Cytotoxic to HIV-infected Cells.” PLOS Pathogens, 2021, DOI: 10.1371/journal.ppat.1010034. Cao, Y. J., Yu, C., Wu, K. L., Wang, X., Liu, D., Tian, Z., Zhao, L., Qi, X., Loredo, A., Chung, A., Xiao, H. “Synthesis of precision antibody conjugates using proximity-induced chemistry.” Theranostics, 2021, 11, 9107. Wu, K. L., Yu, C., Lee, C., Zuo, C., Ball, Z. T., Zhang, X., Xiao, H. “Precision Modification of Native Antibodies.” Bioconjugate Chemistry, 2021, DOI: 10.1021/acs.bioconjchem.1c00342. Tian, Z., Ling, W., Yu, C., Chen, Y., Xu, Z., Bado, I., Loredo, A., Wang, L., Wang, H., Wu, K. L., Zhang, W., Zhang, X., Xiao, H. “Harness the Power of the Antibody to Fight Bone Metastasis.” Science Advances, 2021, DOI: 10.1126/sciadv.abf2051. Ortiz-Rodríguez, L. A., Hoehn, S., Loredo, A., Wang, L., Xiao, H., Crespo-Hernández, C. E. “Electronic Relaxation Pathways in Heavy-Atom-Free Photosensitizers Absorbing Near-Infrared Radiation and Exhibiting High Yields of Singlet Oxygen Generation.” Journal of the American Chemical Society, 2021, DOI: 10.1021/jacs.0c13203. Loredo, A., Wang, L., Shichao, W., Xiao, H. “Single-Atom Switching as a General Approach to Designing Colorimetric and Fluorogenic Probes for Mercury Ions.” Dyes and Pigments, 2021, 186, 109014. Chen, Y., Tang, J., Wang, L. S., Tian, Z., Cardenas, A., Fang, X., Chatterjee, A., Xiao, H. “Creation of Bacterial Cells with 5-Hydroxytryptophan as a 21st Amino Acid Building Block.” Chem, 2020, 6, 1-11. Tang, J.†, Wang, L. S.†, Loredo, A., Cole, C., Xiao, H. “Single-Atom Replacement as a General Approach Towards Visible-Light/Near-Infrared Heavy-Atom-Free Photosensitizers for Photodynamic Therapy.” Chemical Science, 2020, DOI: 10.1039/D0SC02286A. Tang, J.†, Yu, C.†, Loredo, A., Chen, Y., Xiao, H. “VIP: Site‐Specific Incorporation of a Photoactivatable Fluorescent Amino Acid.” ChemBioChem, 2020, DOI: 10.1002/cbic.202000602. Loredo, A.†, Tang, J.†, Wang, L. S., Wu, K. L., Peng, Z., Xiao, H. “Tetrazine as a General Phototrigger to Turn on Fluorophores.” Chemical Science, 2020, DOI: 10.1039/D0SC01009J. Gray, M. A., Stanczak, M. A., Mantuano, N. R., Xiao, H., Pijnenborg, J. F. A., Malaker, S. A., Weidenbacher, P.A., Miller, C. L., Tanzo, J. T., Ahn, G., Woods, E. C., Läubli, H., Bertozzi, C. “Targeted glycan degradation potentiates the anticancer immune response in vivo.” Nature Chemical Biology, 2020, DOI: 10.1038/s41589-020-0622-x. Chen, Y.†, Wu, K. L.†, Pei, J., Tang, J., Loredo, A., Peng, Z., Gupta, R., Xiao, H. “Addition of Isocyanide-containing Amino Acids to the Genetic Code for Protein Labeling and Activation.” ACS Chemical Biology, 2019, DOI: 10.1021/acschembio.9b00678.

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