Prof. Ku-Lung (Ken) Hsu is a chemical biologist that studies protein and lipid activity in human biology and disease. Research conducted in his laboratory is multidisciplinary and uses a combination of organic, bioanalytical, and bioorganic chemistry. His group has developed enabling technologies in the form of covalent probes and inhibitors, and proteomic screening capabilities to help discover new ways for targeting cancer initiation, progression, and resistance.

Prof. Hsu earned his PhD in Chemistry and Biochemistry from the University of Texas at Austin where he trained with Prof. Lara Mahal to pioneer the development of protein microarrays for profiling complex glycosylation on tumor cell surfaces. He pursued further training in chemical biology with Prof. Benjamin Cravatt at The Scripps Research Institute (TSRI) as a Hewitt Foundation for Medical Research Postdoctoral Fellow. At TSRI, Prof. Hsu gained expertise in activity-based protein profiling (ABPP) and mass spectrometry-based lipidomics to discover and functionally annotate lipid-signaling pathways in neurophysiology and immunology.

Prof. Hsu launched his independent career as an Assistant Professor in the Department of Chemistry at the University of Virginia (UVA) in 2015. At UVA, Prof. Hsu and his group used chemistry and chemical biology methods to decipher the biological roles of proteins involved in the metabolism of lipids. Lipids, an understudied class of biomolecules, are ubiquitous chemical signals for basic communication in biology and are valuable targets in medicine. He built an innovative, federally-funded research program (NIH, DOD, NSF) aimed at deciphering the mechanistic basis for specificity of diacylglycerol (DAG) lipid biology. Specifically, his group made important discoveries on DAG signaling in T cells and how to selectively target metabolic enzymes for immunotherapy in cancer. Dr. Hsu was promoted to Associate Professor with tenure in 2020 and is currently a full member of the NCI-designated Comprehensive Cancer Center at UVA. Prof. Hsu's research program has been recognized by several awards including the highly competitive NIH K99/R00 Pathway to Independence Award, Department of Defense CDMRP Career Development Award, Melanoma Research Alliance Young Investigator Award, the NSF CAREER Award, and the Emerging Leader Award from The Mark Foundation for Cancer Research.

Prof. Hsu was recruited to the Department of Chemistry at the University of Texas at Austin in 2022 through a Recruitment of Rising Stars Award from CPRIT. As a CPRIT Scholar, Prof. Hsu aims to apply sulfur-triazole exchange (SuTEx) chemistry developed by his group to tackle a previously unreachable class of proteins. The SuTEx platform utilizes sulfonyl-triazoles as a new covalent binder of tyrosines for basic and translational discovery. The phenol side chain of tyrosines can serve as a nucleophilic site for protein modification by covalent compounds. The amphiphilic nature of the phenol group facilitates location of tyrosines in diverse protein domains involved in catalysis and recognition that can be further regulated through phosphorylation and additional post-translational modifications. These features of tyrosines, combined with the natural low abundance (~2-3%) of this residue, afford exciting opportunities to perturb catalytic and non-catalytic protein function using covalent small molecules. The broader impact of the proposed research is a creative means to reveal and target cancer vulnerabilities by disrupting tumor-specific stress coping mechanisms for precision medicine.