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Chemical Biology & Drug Discovery

holding research tubes

The research interests of our division run the gamut from physical organic chemistry to virology. For example, the group of Leslie Aldrich investigates complex biological phenomena using novel small-molecule probes derived from diversity-oriented synthesis. They develop methods to access synthetic “unnatural product” scaffolds that are reminiscent of biologically active natural products. They also perform high-throughput screening to identify small molecules that modulate complex biological pathways and explore cellular processes that are important in human health using newly discovered small-molecule probes, with the ultimate goal of discovering novel therapeutic strategies for treating diseases.

Wonhwa Cho studies the chemical biology of membranes and membrane-binding proteins that play key roles in cell regulation and are thus implicated in major human diseases. He has been developing novel chemical, physical, computational and analytical research methods and applying them to the study of the mechanisms of cellular protein-protein and protein-lipid interactions both on a single-molecule level and on a systems biology level. Current research projects include bioinformatics-based identification and characterization of lipid binding domains, development of new molecular sensors for lipid quantification, mechanism of membrane deformation by lipid binding domains, and mechanistic studies of cellular signaling proteins in living cells.

Ruixuan (Rui) Gao's group is interested in exploring how basic molecular building blocks, such as proteins, lipids, and RNAs, assemble and interact with one another to achieve particular biological functions or cause dysfunctions. Specifically, Rui's group designs and synthesizes macromolecular matrices, supramolecular assemblies, and chemical linkers/probes to selectively target, detect, and visualize molecular entities and dynamics in cells and tissues. His group is also interested in developing new microscopy and bioimaging methods to map and track these molecular targets at nanoscopic resolution. Moreover, his group seeks to advance and apply spatial-omics-based approaches to complex biological processes and structures in living organisms. Rui's group uses these tools to study structures and processes central to biology and human health, such as the ultrastructure of synapses, chemical profile of synaptic transmission, long-range neuronal connections, and pathological effects of misfolded proteins in neuropathological brains.

Ying Hu's immune imaging group develops ultrasensitive superresolution techniques to reveal previously unseen molecular details in human immunity while creating impactful imaging-driven solutions to improve the standard of care in immuno-oncology. Current research focuses on 1) developing new imaging probes for superresolution molecular quantification, 2) understanding signaling and biomaterial transport in a localized membrane region approximately one-hundredth the size of an immune cell, 3) engineering nanocarriers to modify immune cell behaviors, and 4) leveraging computational approaches to extract immune cell functions. The multidisciplinary research is at the forefront of bioimaging, chemical biology, bioanalytical chemistry, and nanotechnology. In the future, the new technologies may transform the management of diseases, including lymphoproliferative disorders and cytokine release syndrome, while improving disease prevention and therapeutics, including nanocarrier vaccines, immunotherapies, and more.

Larry Miller develops and applies novel chemical and analytical methods to study protein function in living mammalian cells. His experimental approach incorporates synthetic organic chemistry, molecular and cell biology, and microscopy to analyze protein-protein interactions both in vivo and in vitro. Miller Group research interests include the synthesis of small molecules that specifically label recombinant proteins and impart them with unique optical and chemical functionality, the development of time-resolved fluorescence microscopy, and quantitative imaging of protein-protein interactions.