Ku-Lung (Ken) Hsu
Assistant Professor of Chemistry and Pharmacology
Room 388A, Chemistry Building (434) 297-4864
The Hsu laboratory studies immune function and disorders using the principles of chemical biology. We study the immune system because of its ubiquitous role in physiology with the goal of using our findings to provide new insights and treatment options for human disease. We are interested in understanding how cellular phenotype and function is regulated in vivo to produce a robust and specific immune response. Upon activation, immune cells undergo global changes in cell physiology that result in acquisition of new functions including massive production of lipid and protein signals and alterations in cell proliferation and migration. In contrast, aberrant immune responses result in damage to host and can lead to excessive inflammation in disease states including cancer, metabolic syndrome, and autoimmune disorders. Central to this cellular plasticity are poorly understood metabolic and signaling pathways that support or direct immune response outcome.
Our research group focuses on developing chemical methods and probes to advance our understanding of biochemical pathways underlying immune function in mammalian systems. To achieve our goals, we integrate state-of-the-art chemical and mass spectrometry-based technologies to enable metabolic and pathophysiological measurements of enzyme-disrupted cells and animals.
Current research efforts are directed towards the following topics:
1. Lipid metabolism and signaling in inflammation
2. Cancer immunotherapy
3. Post-translational regulation of immune cell phenotype
Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes. Dominguez E, Galmozzi A, Chang JW, Hsu KL, Pawlak J, Li W, Godio C, Thomas J, Partida D, Niessen S, O’Brien PE, Russell AP, Watt MJ, Nomura DK, Cravatt BF, and Saez E. Nature Chemical Biology 10, 113-121 (2014).
Discovery and optimization of piperidyl-1,2,3-triazole ureas as potent, selective, and in vivo-active inhibitors of alpha/beta-hydrolase domain containing 6 (ABHD6). Hsu KL, Tsuboi K, Chang JW, Whitby LR, Speers AE, Pugh H, and Cravatt BF. Journal of Medicinal Chemistry 56, 8270-8279 (2013).
Development and optimization of piperidyl-1,2,3-triazole ureas as selective chemical probes of endocannabinoid biosynthesis. Hsu KL, Tsuboi K, Whitby LR, Speers AE, Pugh H, Inloes J, and Cravatt BF. Journal of Medicinal Chemistry 56, 8257-8269 (2013).
DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses. Hsu KL, Tsuboi K, Adibekian A, Pugh H, Masuda K, and Cravatt BF. Nature Chemical Biology 8, 999-1007 (2012).
Click-generated triazole ureas as ultrapotent in vivo-active serine hydrolase inhibitors. Adibekian A, Martin BR, Wang C, Hsu KL, Bachovchin DA, Niessen S, Hoover H, and Cravatt BF. Nature Chemical Biology 7, 469-478 (2011).