Xiao, Han - Rice University - Department of Chemistry

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Xiao, Han Professor 收藏完善纠错
Rice University Department of Chemistry

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 David W. Robertson Award for Excellence in Medicinal Chemistry, ACS, 2026 Provost's Award for Outstanding Early-Career Achievement, Rice University, 2025 ACS Bioconjugate Chemistry Young Investigator Award, ACS, 2025 Medical Research Award, Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, 2025 Breast Cancer Research Program Breakthrough Award – Level 2, Department of Defense, 2025 Maximizing Investigators’ Research Award for Established Investigators, NIH, 2024 ACS Bio & Med Chem Au’s 2024 Rising Star in Biological, Medicinal, and Pharmaceutical Chemistry, 2024 Breast Cancer Research Program (BCRP) Breakthrough Award – Level 2, Department of Defense, 2023 CAPA Distinguished Junior Faculty Award, Chinese-American Chemistry & Chemical Biology Professors Association, 2023 Breast Cancer Research Program (BCRP) Breakthrough Award – Level 2, Department of Defense, 2021 Maximizing Investigators’ Research Award for Early Stage Investigators (MIRA), NIH, 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 Biography Han Xiao serves as the Director of the SynthX Center and holds the position of Associate Professor within the Department of Chemistry, Biosciences, and Bioengineering at Rice University. Han 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. 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 Stanford University. In his postdoctoral work, he was engaged in the development of novel cancer immune therapy targeting the cell-surface glycans axis of immune modulation. In July 2017, Han started his independent research at Rice University. The focus of his research is the development of various chemical biological tools allowing us to understand complex biological systems as well as develop novel therapeutic strategies. His awards include Level 2 Breast Cancer Research Program Breakthrough Award (DoD), Maximizing Investigators’ Research Award for Early Stage Investigators (NIH), Norman Hackerman - Welch Young Investigator Award, and CPRIT Faculty Recruitment Award.

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. First-in-Class Therapies for Bone Diseases The skeletal system provides structural support and maintains mineral homeostasis, but it also plays a critical role in the progression of diseases such as cancer metastasis, autoimmune disorders, and hematologic malignancies. Breast and prostate cancers are the most common sources of bone metastases; over 47% of initial metastatic events occur in bone, and about 80% of prostate cancer metastases are confined to the skeleton. However, effective drug delivery to bone remains a challenge, limiting current treatment efficacy. To address this, my lab developed BonTarg, a bone-targeting platform that enables site-specific conjugation of bone-homing moieties to therapeutic antibodies. This approach enhances antibody accumulation in bone metastases while minimizing off-target effects. We also identified a novel glyco-immune checkpoint in the bone tumor microenvironment and showed that antibody blockade suppresses tumor-induced bone damage and boosts T cell responses. These advances support a dual strategy—targeted delivery and immune modulation—for treating bone-metastatic cancers. We are further expanding this platform to deliver small molecules, epigenetic inhibitors, bispecific antibodies, and cell therapies to the bone niche. Machine Learning-Based Protein Evolution Machine learning has brought about a paradigm shift in protein evolution, facilitating swift and precise projections of protein structures, functions, and interactions. This advancement accelerates the innovation of novel enzymes, therapeutic agents, and biomolecules endowed with amplified attributes and custom functionalities. A present challenge lies in swiftly amassing sequence-function data for a target protein. To address this, we are devising a comprehensive approach that employs next-generation sequencing (NGS) to acquire functional information for an array of target proteins. Integrating this resultant sequence-function dataset with neural networks, we aim to engineer new proteins possessing attributes surpassing those found in natural sequences. Biomedical Probes for Noninvasive Deep-Tissue Imaging Compared to traditional imaging, NIR-II, bioluminescence, and photoacoustic imaging offer deeper tissue penetration with reduced photon scattering and autofluorescence, making them powerful tools for noninvasive biomedical imaging. However, probes suitable for these modalities remain limited, especially those capable of crossing the blood-brain barrier or entering the lymphatic system. To address this gap, we are developing advanced functional imaging probes for in vivo NIR-II imaging and photoacoustic computed tomography. These probes are designed to achieve high spatial resolution, target specificity, and favorable biodistribution, enabling precise and dynamic visualization of deep tissues in both research and potential clinical applications.

近期论文

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Teng, Y., Zhang, M., Cheng, L., Zheng, X., Jiang, S., Huang, X. , Xiao, H. “Biocatalytic Synthesis of N-protected α-Amino Acids through 1,3-Nitrogen Migration by Nonheme Iron Enzymes.” Journal of the American Chemical Society, 2025, DOI: 10.1021/jacs.5c11008. Singh, S., Islam, S. S., Liu, R., Adeniji, O. S., Simons, L. M., Saini, P., Tateno, H., Danesh, A., Denton, P. W., Giron, L. B., Jones, B., Hultquist, J. F., Xiao, H., Abdel-Mohsen, Mohamed, H. “HIV-Induced Sialoglycans on Infected CD4+ T Cells Promote Immune Evasion from Myeloid Cell-Mediated Killing.” Nature Communications, 2025, DOI: 10.1038/s41467-025-66540-y. Hu, Y., Wang, Y., Cheng, L., Wang, C., Liu, Y., Wang, Y., Chen, Y., Yang, S., Guo, Y., Jiang, S., Yang, K., Xiao, H. “Engineering Unnatural Cells with a 21st Amino Acid as a Living Epigenetic Sensor.” Nature Communications, 2025, accepted in principle. Hu, Y., Cheng, L., Liu, Y., Liu, R., Jiang, S., Yuan, T., Wang, Y., Ye, H., Xiao, H. “Biosynthesis of Unnatural Cyclodipeptides through Genetic Code Expansion and Cyclodipeptide Synthesis Evolution.” Journal of the American Chemical Society, 2025, DOI: 10.1021/jacs.5c08627. Yang, S., Jin, S., Zhang, M., Chen, Y., Guo, Y., Hu, Y, Wolynes, P. G., Xiao, H. “Real-Time Visualization of Protein Microenvironment Changes with High Spatial Resolution in Live Cells via Site-Specific Incorporation of Rotor-Based Fluorescent Noncanonical Amino Acids.” Nature Chemical Biology, 2025, DOI: 10.1038/s41589-025-02003-1. Hu, Y., Zhang, M., Xiao, H. “Biosynthesis of Nitrile-Containing Amino Acids for Rapid Protein Conjugation and Fluorogenic Labeling.” Chem, 2025, DOI: 10.1016/j.chempr.2025.102573. Lu, K., Zhang, M., Tian, Z., Xiao, H. “Real-Time Bioluminescence Imaging of Nitroreductase in Breast cancer bone metastasis.” RSC Chemical Biology, 2025, DOI: 10.1039/D4CB00310A. Bado, I. L.*, Edwards, D. G., Lege, B. M.., Hao X., Arcos, L. M., Reduzzi, C., Wu, Y., Tian, Z., Nirmalakumar, S., Reva, A., Alam, R., Ntalee, L. M., Damle, G., Demirciouglu, D., Wang, Y., Wu, L., Hasson, D., Lim, B., Gugala, Z., Cheng, C., Cristofanilli, M., Xiao, H., Zhang, X., Chipuk, J., Lang, J., Sporano, J., and Molteni, E. “Bone-Induced Her2 Promotes Secondary Metastasis in HR+/Her2- Breast Cancer.” Cancer Discovery, 2025, DOI: 2159-8290.CD-23-0543. Lu, K., Wang, Y., Wang, C., Liu, R., Yang, K., Zhang, X., Xiao, H. “A Bioluminescent Probe for Highly Selective Detection of H2S in the Tumor Microenvironment.” ACS Bio & Med Chem Au, 2025, DOI: acsbiomedchemau.4c00102. Acquah, C., Hoehn, S., Krul, S., Yang, S., Seth, S. K., Lee, E., Jockusch, S., Xiao, H., and Crespo-Hernández, C. E. “Electronic relaxation pathways in thio-acridone and thio-coumarin: two heavy-atom-free photosensitizers absorbing visible light.” Physical Chemistry Chemical Physics, 2024, DOI: 10.1039/D4CP03720K. Zhang, M., Chen, Y., Chung, A., Yang, S., Choi, C. H., Zhang, S., Han, Y., Xiao, H. “Harnessing Nature-Inspired Catechol Amino Acid to Engineer Sticky Proteins and Bacteria.” Small Methods, 2024, DOI: 10.1002/smtd.202400230. Yang, S., Lu, K., Xiao, H. “Advancements in Boron Difluoride Formazanate Dyes for Biological Imaging.” Current Opinion in Chemical Biology, 2024, DOI: 10.1016/j.cbpa.2024.102473. Ding, Y., Pedersen, S. S., Wang, H., Xiang, B., Wang, Y., Yang, Z., Gao, Y., Morosan, E., Jones, M. R., Xiao, H., Ball, Z. T. “Selective Macrocyclization of Unprotected Peptides with an Ex Situ Gaseous Linchpin Reagent.” Angewandte Chemie International Edition, 2024, DOI: 10.1002/anie.202405344. Guo, Y., Cheng, L., Hu, Y., Zhang, M., Rui, L., Wang, Y., Jiang, S., Xiao, H. “Biosynthesis of Halogenated Tryptophans for Protein Engineering using Genetic Code Expansion.” ChemBioChem, 2024, DOI: 10.1016/j.cbpa.2024.102473. Shen, Q., Li, Z., Wang, Y., Meyer, M. D., Guzman, M. T., Lim, J. C., Xiao, H., Lu, G. J. “50-nm Gas-Filled Protein Nanostructures to Enable the Access of Lymphatic Cells by Ultrasound Technology.” Advanced Materials, 2024, DOI: 10.1002/adma.202307123. [pdf] Wang, Y., Wang, C., Xia, M., Tian, Z., Zhou, J., Berger, J. M., Zhang, X., Xiao, H. “Engineered Small Molecule and Protein Drugs for Targeting Bone Tumors.” Molecular Therapy, 2024, DOI: 10.1016/j.ymthe.2024.03.001. 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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