Haotian Du

All Publications

• A general platform for targeting MHC-II antigens via a single loop. bioRxiv : the preprint server for biology Du, H., Liu, J., Jude, K. M., Yang, X., Li, Y., Bell, B., Yang, H., Kassardjian, A., Mobedi, A., Parekh, U., Sperberg, R. A., Julien, J. P., Mellins, E. D., Garcia, K. C., Huang, P. S. 2024

  Abstract

  Class-II major histocompatibility complexes (MHC-IIs) are central to the communications between CD4+ T cells and antigen presenting cells (APCs), but intrinsic structural features associated with MHC-II make it difficult to develop a general targeting system with high affinity and antigen specificity. Here, we introduce a protein platform, Targeted Recognition of Antigen-MHC Complex Reporter for MHC-II (TRACeR-II), to enable the rapid development of peptide-specific MHC-II binders. TRACeR-II has a small helical bundle scaffold and uses an unconventional mechanism to recognize antigens via a single loop. This unique antigen-recognition mechanism renders this platform highly versatile and amenable to direct structural modeling of the interactions with the antigen. We demonstrate that TRACeR-II binders can be rapidly evolved across multiple alleles, while computational protein design can produce specific binding sequences for a SARS-CoV-2 peptide of unknown complex structure. TRACeR-II sheds light on a simple and straightforward approach to address the MHC peptide targeting challenge, without relying on combinatorial selection on complementarity determining region (CDR) loops. It presents a promising basis for further exploration in immune response modulation as well as a broad range of theragnostic applications.

  View details for DOI 10.1101/2024.01.26.577489

  View details for PubMedID 38352315

  View details for PubMedCentralID PMC10862749

• In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles. Nature biotechnology Zhong, Y., Ma, Z., Wang, F., Wang, X., Yang, Y., Liu, Y., Zhao, X., Li, J., Du, H., Zhang, M., Cui, Q., Zhu, S., Sun, Q., Wan, H., Tian, Y., Liu, Q., Wang, W., Garcia, K. C., Dai, H. 2019

  Abstract

  The near-infrared-IIb (NIR-IIb) (1,500-1,700nm) window is ideal for deep-tissue optical imaging in mammals, but lacks bright and biocompatible probes. Here, we developed biocompatible cubic-phase (alpha-phase) erbium-based rare-earth nanoparticles (ErNPs) exhibiting bright downconversion luminescence at ~1,600nm for dynamic imaging of cancer immunotherapy in mice. We used ErNPs functionalized with cross-linked hydrophilic polymer layers attached to anti-PD-L1 (programmed cell death-1 ligand-1) antibody for molecular imaging of PD-L1 in a mouse model of colon cancer and achieved tumor-to-normal tissue signal ratios of ~40. The long luminescence lifetime of ErNPs (~4.6ms) enabled simultaneous imaging of ErNPs and lead sulfide quantum dots emitting in the same ~1,600nm window. In vivo NIR-IIb molecular imaging of PD-L1 and CD8 revealed cytotoxic T lymphocytes in the tumor microenvironment in response to immunotherapy, and altered CD8 signals in tumor and spleen due to immune activation. The cross-linked functionalization layer facilitated 90% ErNP excretion within 2weeks without detectable toxicity in mice.

  View details for DOI 10.1038/s41587-019-0262-4

  View details for PubMedID 31570897

• Molecular imaging in the second near-infrared window. Advanced functional materials Wan, H., Du, H., Wang, F., Dai, H. 2019; 29 (25)

  Abstract

  In the past decade, noticeable progress has been achieved regarding fluorescence imaging in the second near-infrared (NIR-II) window. Fluorescence imaging in the NIR-II window demonstrates superiorities of deep tissue penetration and high spatial and temporal resolution, which are beneficial for profiling physiological processes. Meanwhile, molecular imaging has emerged as an efficient tool to decipher biological activities on the molecular and cellular level. Extending molecular imaging into the NIR-II window would enhance the imaging performance, providing more detailed and accurate information of the biological system. In this progress report, selected achievements made in NIR-II molecular imaging are summarized. The organization of this report is based on strategies underlying rational designs of NIR-II imaging probes and their applications in molecular imaging are highlighted. This progress report may provide guidance and reference for further development of functional NIR-II probes designed for high-performance molecular imaging.

  View details for DOI 10.1002/adfm.201900566

  View details for PubMedID 31885529

  View details for PubMedCentralID PMC6934177

• Light-sheet microscopy in the near-infrared II window NATURE METHODS Wang, F., Wan, H., Ma, Z., Zhong, Y., Sun, Q., Tian, Y., Qu, L., Du, H., Zhang, M., Li, L., Ma, H., Luo, J., Liang, Y., Li, W., Hong, G., Liu, L., Dai, H. 2019; 16 (6): 545-+

  View details for DOI 10.1038/s41592-019-0398-7

  View details for Web of Science ID 000469455200024

• Molecular Imaging in the Second Near-Infrared Window ADVANCED FUNCTIONAL MATERIALS Wan, H., Du, H., Wang, F., Dai, H. 2019; 29 (25)

  View details for DOI 10.1002/adfm.201900566

  View details for Web of Science ID 000472552900017