Peng Wu, PhD
Scripps Research Joint Appointments
Research Focus
The research in the Wu laboratory integrates synthetic chemistry with glycobiology to explore the cellular and molecular mechanisms that control immune responses toward cancer and human pathogens.
Cell-cell interactions play critical roles during immune responses against cancer and human pathogens, in which the productive interaction of antigen-presenting cells and T cells is required for the successful priming of "adaptive" T-cell responses. On the other hand, chronic antigen stimulation leads to T-cell dysfunction. Bystander T cells that recognize irrelevant antigens are also enlisted in such pathological processes. However, we know little about the precise contributions of endogenous antigen-specific and bystander T cells during the course of a natural pathogen infection and cancer progression. Due to their heterogeneous compositions, it is challenging to elucidate their properties.
The focus of my lab is to develop new chemical approaches to probe cell-cell interactions in these processes. We are interested in detecting endogenous antigen-specific T cells and separating them from bystander T cells with the goal of understanding the specific roles and functional differences of these two T-cell subsets in an immune response, how T cells’ reactivity is linked to their functional state, and how to improve persistence and replication potential of antigen-specific T cells for treating infection and cancer.
Molecules presented on the cell surface determine how cells interact with their partners and their environment. In the cancer-immunity cycle, a process initiated by the release of cancer cell antigens and ended with the destruction of cancer cells, the interaction of Siglecs (Sialic-acid-binding immunoglobulin-type lectins) with sialylated glycan ligands modulates immune cell-tumor cell interactions, triggering signaling cascades to inhibit anti-tumor immune responses. We are developing unnatural Siglec ligands using sulfur (VI) fluoride exchange (SuFEx) click chemistry to explore if ligands with sufficiently high affinity and specificity can be identified to block the endogenous Siglec–ligand binding at the immunological synapse formed between immune cells and target cells and if such ligands can be employed to engineer immune cells with desired properties for therapeutic applications.
Education
Ph.D. (Chemistry), Scripps Research, 2005M.S. (Chemistry), Indiana University, 2001
B.S. (Chemistry), Peking University, 1999
Professional Experience
2017-2018 Associate Professor, Molecular Medicine, Scripps Research2015-2017 Associate Professor, Chemical Physiology, Scripps Research
2014-2015 Visiting Investigator, Chemistry, Scripps Research
2013-2014 Associate Professor, Albert Einstein College of Medicine
2011-2014 Scientific Director of the Chemical Biology Core Facility, Albert Einstein College of Medicine
2013-2013 Visiting Fellow, Pembroke College, University of Oxford
2008-2013 Assistant Professor, Albert Einstein College of Medicine
2005-2008 Postdoctoral Associate, University of California, Berkeley
Awards & Professional Activities
Selected References
Detecting Tumor Antigen-specific T cells via Interaction Dependent Fucosyl-biotinylation. Liu, Z.; Li, J.P.; Chen, M.; Wu, M.; Shi, Y.; Li, W.; Teijaro, J.R.; Wu, P. Cell, 2020, https://doi.org/10.1016/j.cell.2020.09.048
Glycoengineering of NK cells with Glycan Ligands of CD22 and Selectins for B-cell Lymphoma Therapy. Hong, S.; Yu, C.; Wang, P.; Shi, Y.; Cheng, B.; Chen, M.; Chapla, D.G.; Reigh, N.; Narimatsu, Y.; Chen, X.; Clausen, H.; Moremen, K.W.; Macauley, M.S.; Paulson, J.C.; Wu, P. BioRxiv 2020, March 25. doi: 10.1101/2020.03.23.004325.
In Situ Fucosylation of the Wnt Co-receptor LRP6 Increases Its Endocytosis and Reduces Wnt/β-Catenin Signaling Hong, S.; Feng, L.; Jiang, H.; Hou, X.; Guo, P.; Marlow, F. L.; Stanley, P.; Wu, P. Cell. Chem. Biol. 2020, doi: 10.1016/j.chembiol.2020.06.015.
Direct Visualization of Live Zebrafish Glycan via Single-step Metabolic Labeling with Fluorophore-tagged Nucleotide Sugars. Hong, S.; Sahai-Hernandez, P.; Chapla, D.G.; Moremen, K.W.; Traver, D.; Wu, P. Angew. Chem. Int. Ed. 2019, 58, 14327.
Bacterial Glycosyltransferase-mediated Cell-surface Chemoenzymatic Glycan Modification. Hong, S.; Shi, Y.; Wu, N. C.; Grande, G.; Douthit, L.; Wang, H.; Zhou, W.; Sharpless, K. B.; Wilson, I. A.; Xie, J.; Wu, P. Nat. Commun. 2019, 10, 1799.
Single-step Enzymatic Glycoengineering for the Construction of Antibody-cell Conjugates. Li, J.; Chen, M.; Liu, Z.; Zhang, L.; Felding, B.H.; Lauvau, G.; Abadier, M.; Ley, K.; Wu, P. ACS Cent Sci. 2018, 4, 1633-1641.
Cell-Based Glycan Arrays for Probing Glycan–Glycan Binding Protein Interactions. Briard, J.G., Jiang, H., Moremen, K.W., Macauley, M.S., Wu, P. Nat. Commun. 2018, 9, 880.
Engineered glycocalyx regulates stem cell proliferation in murine crypt organoids. Rouhanifard, S.H.; Aguilar Lopez, A.; Meng, L.; Moremen, K.W.; Wu,P. Cell. Chem. Bio. 2018, 25, 439
Modulating cell-surface receptor signaling and ion channel functions by in situ glycan editing. Jiang, H.; Meng, L.; Lopez-Aguilar, A.; Gao, Z.; Liu, Y.; Tian, X.; Yu, G.; Ovryn, B.; Moremen, K.W.; Wu, P. Angew. Chem. Int. Ed. 2018, 57, 967.
Inhibition of Delta-induced Notch Signaling Using Fucose Analogs. Schneider, M.; Kumar, V.; Nordstrøm, L.; Feng, L.; Takeuchi, H.; Stanley, P.; Wu, P.*; Haltiwanger, R. S.* Nat. Chem. Biol. 2018, 14, 65, (*co-corresponding authors).
Profiling of Protein O-GlcNAcylation in Murine CD8+ Effector- and Memory-like T Cells. Lopez Aguilar, A.; Gao, Y.; Hou, X.; Lauvau, G.; Yates, J.R.; Wu, P. ACS Chem. Biol. 2017, 12, 3031.
Bifluoride-catalyzed Sulfur(VI) Fluoride Exchange (SuFEx) Reaction for the Synthesis of Polysulfates and Polysulfonates. Gao, B.; Zhang, L.; Zheng, Q.; Zhou, F.; Klivansky, L. M.; Lu, J.; Liu, Y.; Dong J.*; Wu, P.*; Sharpless, K. B.* Nat. Chem. 2017, 9, 1083. (*co-corresponding authors).
Tracking Surface Glycans on Live Cancer Cells with Single Molecule Sensitivity. Jiang, H.; English, B.; Hazan, R.; Wu, P.;* Ovryn, B.* Angew. Chem. Int. Ed. 2015, 93, 21.
Biocompatible Click Chemistry Enabled Compartment-Specific pH Measurement Inside E. coli. Yang, M.; Jalloh, A.; Wei, W. Zhao, J.*; Wu. P*; Chen, P.R.* Nat. Commun. 2014, 5, Article number: 4981; doi:10.1038/ncomms5981
In vivo chemistry. Bertozzi, C. R.; Wu, P. Curr. Opin. Chem, Biol. 2013, 17, 717.
Chemical Probing of Glycans in Cells and Organisms. Rouhanifard, S. H.; Nordstrom, L. U.; Zheng, T.; Wu, P. Chem. Soc. Rev. 2013, 42, 4284.
Tracking N-acetyllactosamine on Cell Surface Glycans in Vivo. Zheng, T.; Jiang, H.; Gros, M., Soriano del Amo, D.; Sundaram, S.; Lauvau, G.; Marlow, F.; Liu, Y., Stanley, P.; Wu, P. Angew. Chem. Int. Ed. 2011, 50, 4113.
Links
C&En News “Targeting tumor-specific T cells”
Accelerating Cancer Immunotherapy Research (ACIR) Spotlight
Exposed: cells’ sugary secrets
Sugar-transferring Enzyme Adds Antibody to Cell Surface
Glycan Arrays Created with Live Cells
Making Polymer Chemistry ‘Click’
Single Glycoproteins Caught In Motion