Dr. Hsu is developing a chemical technology that can selectively enrich, quantify, and pharmacologically target different molecular forms of oncogenic proteins based on their tyrosine phosphorylation (pTyr) state. This research is needed to complement large-scale patient sequencing initiatives — to understand and identify driver mutations that have biological and clinical importance. In this project, Dr. Hsu’s team is combining innovative chemical biology and proteomics approaches, including a covalent chemical probe platform developed in his lab known as SuTEx that is specific for tyrosines, to detect and selectively perturb low abundance pTyr sites on oncogenic proteins. This work aims to establish tyrosine mutational hotspots as a new target for development of cancer drugs and gain fundamental understanding of pTyr dysfunction in cancer signaling.
Dr. Hsu earned his PhD in Chemistry and Biochemistry from the University of Texas at Austin and completed his postdoctoral training at The Scripps Research Institute.
PUBLISHED RESEARCH
Grams RJ, Hsu KL. Reactive chemistry for covalent probe and therapeutic development. Trends Pharmacol Sci. 2022.
Ciancone AM, Hosseinibarkooie S, Bai DL, Borne AL, Ferris HA, Hsu KL. Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation. Cell Chem Biol. 2022.
Ciancone AM, Seo KW, Chen M, Borne AL, Libby AH, Bai DL, Kleiner RE, Hsu KL. Global Discovery of Covalent Modulators of Ribonucleoprotein Granules. J Am Chem Soc. 2023.
Mendez R, Shaikh M, Lemke MC, Yuan K, Libby AH, Bai DL, Ross MM, Harris TE, Hsu KL. Predicting small molecule binding pockets on diacylglycerol kinases using chemoproteomics and AlphaFold. RSC Chem Biol. 2023.
Heindel AJ, Brulet JW, Wang X, Founds MW, Libby AH, Bai DL, Lemke MC, Leace DM, Harris TE, Hafner M, Hsu KL. Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023.
Chen M, Shin M, Ware TB, Donvito G, Muchhala KH, Mischel R, Mustafa MA, Serbulea V, Upchurch CM, Leitinger N, Akbarali HI, Lichtman AH, Hsu KL. Endocannabinoid biosynthetic enzymes regulate pain response via LKB1-AMPK signaling. Proc Natl Acad Sci U S A. 2023.