Peng Wu, PhD

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.