Ku-Lung Hsu
- Email: kh4ch@virginia.edu
- Phone: 434-297-4864
- Website: http://hsulab.com
Primary Appointment
Associate Professor, Chemistry
Research Disciplines
Biochemistry, Biophysics, Biotechnology, Cancer Biology, Chemistry, Immunology, Metabolism, Molecular Pharmacology, Translational Science
Research Interests
Chemical Biology, Lipid Biochemistry, Medicinal Chemistry, and Mass Spectrometry
Research Description
Personal Statement
Training
- Biotechnology Training Grant
- Cancer Research Training in Molecular Biology
- Predoctoral Training in Neuroscience
- Training in Molecular Biophysics
- Training in the Pharmacological Sciences
Selected Publications
2020
Brulet, J. W., Borne, A. L., Yuan, K., Libby, A. H., & Hsu, K. -L. (2020). Liganding Functional Tyrosine Sites on Proteins Using Sulfur- Triazole Exchange Chemistry. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 142(18), 8270-8280. doi:10.1021/jacs.0c00648
Shin, M., Ware, T. B., & Hsu, K. -L. (2020). DAGL-Beta Functions as a PUFA-Specific Triacylglycerol Lipase in Macrophages. CELL CHEMICAL BIOLOGY, 27(3), 314-+. doi:10.1016/j.chembiol.2020.01.005
Ware, T. B., Franks, C. E., Granade, M. E., Zhang, M., Kim, K. -B., Park, K. -S., . . . Hsu, K. -L. (2020). Reprogramming fatty acyl specificity of lipid kinases via C1 domain engineering. NATURE CHEMICAL BIOLOGY, 16(2), 170-+. doi:10.1038/s41589-019-0445-9
Yin, B., Mendez, R., Zhao, X. -Y., Rakhit, R., Hsu, K. -L., & Ewald, S. E. (2020). Automated Spatially Targeted Optical Microproteomics (autoSTOMP) to Determine Protein Complexity of Subcellular Structures. ANALYTICAL CHEMISTRY, 92(2), 2005-2010. doi:10.1021/acs.analchem.9b04396
Hahm, H. S., Toroitich, E. K., Borne, A. L., Brulet, J. W., Libby, A. H., Yuan, K., . . . Hsu, K. -L. (2020). Global targeting of functional tyrosines using sulfur-triazole exchange chemistry. NATURE CHEMICAL BIOLOGY, 16(2), 150-+. doi:10.1038/s41589-019-0404-5
2019
Yin, B., Mendez, R., Zhao, X., Rahkit, R., Hsu, K. -L., & Ewald, S. (2019). Automated Spatially Targeted Optical Micro Proteomics (autoSTOMP) to determine protein complexity of subcellular structures. doi:10.1101/783340
Franks, C. E., & Hsu, K. -L. (2019). Activity-Based Kinome Profiling Using Chemical Proteomics and ATP Acyl Phosphates.. Current protocols in chemical biology, 11(3), e72. doi:10.1002/cpch.72
Ware, T. B., Shin, M., & Hsu, K. -L. (2019). Metabolomics analysis of lipid metabolizing enzyme activity. POST-TRANSLATIONAL MODIFICATIONS THAT MODULATE ENZYME ACTIVITY, 626, 407-428. doi:10.1016/bs.mie.2019.06.027
Lazo, J. S., Blanco, I. K., Tasker, N. R., Rastelli, E. J., Burnett, J. C., Garrott, S. R., . . . Sharlow, E. R. (2019). Next-Generation Cell-Active Inhibitors of the Undrugged Oncogenic PTP4A3 Phosphatase. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 371(3), 652-662. doi:10.1124/jpet.119.262188
Shin, M., Buckner, A., Prince, J., Bullock, T. N. J., & Hsu, K. -L. (2019). Diacylglycerol Lipase-β Is Required for TNF-α Response but Not CD8+ T Cell Priming Capacity of Dendritic Cells. CELL CHEMICAL BIOLOGY, 26(7), 1036-+. doi:10.1016/j.chembiol.2019.04.002
Shin, M., Ware, T. B., Lee, H. -C., & Hsu, K. -L. (2019). Lipid-metabolizing serine hydrolases in the mammalian central nervous system: endocannabinoids and beyond. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1864(6), 907-921. doi:10.1016/j.bbalip.2018.08.007
Borne, A. L., Huang, T., McCloud, R. L., Pachaiyappan, B., Bullock, T. N. J., & Hsu, K. -L. (2019). Deciphering T Cell Immunometabolism with Activity-Based Protein Profiling. ACTIVITY-BASED PROTEIN PROFILING, 420, 175-210. doi:10.1007/82_2018_124
2018
Manterola, A., Bernal-Chico, A., Cipriani, R., Ruiz, A., Perez-Samartin, A., Moreno-Rodriguez, M., . . . Mato, S. (2018). Re-examining the potential of targeting ABHD6 in multiple sclerosis: Efficacy of systemic and peripherally restricted inhibitors in experimental autoimmune encephalomyelitis. NEUROPHARMACOLOGY, 141, 181-191. doi:10.1016/j.neuropharm.2018.08.038
Campbell, S. T., Franks, C. E., Borne, A. L., Shin, M., Zhang, L., & Hsu, K. -L. (2018). Chemoproteomic Discovery of a Ritanserin-Targeted Kinase Network Mediating Apoptotic Cell Death of Lung Tumor Cells. MOLECULAR PHARMACOLOGY, 94(5), 1246-1255. doi:10.1124/mol.118.113001
Manterola, A., Bernal-Chico, A., Cipriani, R., Canedo-Antelo, M., Moreno-Garcia, A., Martin-Fontecha, M., . . . Mato, S. (2018). Deregulation of the endocannabinoid system and therapeutic potential of ABHD6 blockade in the cuprizone model of demyelination. BIOCHEMICAL PHARMACOLOGY, 157, 189-201. doi:10.1016/j.bcp.2018.07.042
Shin, M., Franks, C. E., & Hsu, K. -L. (2018). Isoform-selective activity-based profiling of ERK signaling. CHEMICAL SCIENCE, 9(9), 2419-2431. doi:10.1039/c8sc00043c
Curry, Z. A., Wilkerson, J. L., Bagdas, D., Kyte, S. L., Patel, N., Donvito, G., . . . Lichtman, A. H. (2018). Monoacylglycerol Lipase Inhibitors Reverse Paclitaxel-Induced Nociceptive Behavior and Proinflammatory Markers in a Mouse Model of Chemotherapy-Induced Neuropathy. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 366(1), 169-183. doi:10.1124/jpet.117.245704
Wilkerson, J. L., Curry, Z. A., Kinlow, P. D., Mason, B. L., Hsu, K. -L., van der Stelt, M., . . . Lichtman, A. H. (2018). Evaluation of different drug classes on transient sciatic nerve injury-depressed marble burying in mice. PAIN, 159(6), 1155-1165. doi:10.1097/j.pain.0000000000001199
McCloud, R. L., Franks, C. E., Campbell, S. T., Purow, B. W., Harris, T. E., & Hsu, K. -L. (2018). Deconstructing Lipid Kinase Inhibitors by Chemical Proteomics. BIOCHEMISTRY, 57(2), 231-236. doi:10.1021/acs.biochem.7b00962
Shin, M., Snyder, H. W., Donyito, G., Schurman, L. D., Fox, T. E., Lichtman, A. H., . . . Hsu, K. -L. (2018). Liposomal Delivery of Diacylglycerol Lipase-Beta Inhibitors to Macrophages Dramatically Enhances Selectivity and Efficacy in Vivo. MOLECULAR PHARMACEUTICS, 15(3), 721-728. doi:10.1021/acs.molpharmaceut.7b00657
2017
Yun, B., Lee, H., Powell, R., Reisdorph, N., Ewing, H., Gelb, M. H., . . . Leslie, C. C. (2017). Regulation of calcium release from the endoplasmic reticulum by the serine hydrolase ABHD2. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 490(4), 1226-1231. doi:10.1016/j.bbrc.2017.06.195
Franks, C. E., Campbell, S. T., Purow, B. W., Harris, T. E., & Hsu, K. -L. (2017). The Ligand Binding Landscape of Diacylglycerol Kinases. CELL CHEMICAL BIOLOGY, 24(7), 870-+. doi:10.1016/j.chembiol.2017.06.007
2016
Buczynski, M. W., Herman, M. A., Hsu, K. -L., Natividad, L. A., Irimia, C., Polis, I. Y., . . . Parsons, L. H. (2016). Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113(4), 1086-1091. doi:10.1073/pnas.1522672113
Wilkerson, J. L., Ghosh, S., Bagdas, D., Mason, B. L., Crowe, M. S., Hsu, K. L., . . . Lichtman, A. H. (2016). Diacylglycerol lipase β inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain. BRITISH JOURNAL OF PHARMACOLOGY, 173(10), 1678-1692. doi:10.1111/bph.13469
2015
Baggelaar, M. P., Chameau, P. J. P., Kantae, V., Hummel, J., Hsu, K. -L., Janssen, F., . . . van der Stelt, M. (2015). Highly Selective, Reversible Inhibitor Identified by Comparative Chemoproteomics Modulates Diacylglycerol Lipase Activity in Neurons. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 137(27), 8851-8857. doi:10.1021/jacs.5b04883
Chang, J. W., Zuhl, A. M., Speers, A. E., Niessen, S., Brown, S. J., Mulvihill, M. M., . . . Cravatt, B. F. (2015). Selective Inhibitor of Platelet-Activating Factor Acetylhydrolases 1b2 and 1b3 That Impairs Cancer Cell Survival. ACS CHEMICAL BIOLOGY, 10(4), 925-932. doi:10.1021/cb500893q
Kohnz, R. A., Mulvihill, M. M., Chang, J. W., Hsu, K. -L., Sorrentino, A., Cravatt, B. F., . . . Nomura, D. K. (2015). Activity-Based Protein Profiling of Oncogene-Driven Changes in Metabolism Reveals Broad Dysregulation of PAFAH1B2 and 1B3 in Cancer. ACS CHEMICAL BIOLOGY, 10(7), 1624-1630. doi:10.1021/acschembio.5b00053
2014
Dominguez, E., Galmozzi, A., Chang, J. W., Hsu, K. -L., Pawlak, J., Li, W., . . . Saez, E. (2014). integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes. NATURE CHEMICAL BIOLOGY, 10(2), 113-121. doi:10.1038/nchembio.1429
Yun, B., Lee, H., Ghosh, M., Cravatt, B. F., Hsu, K. -L., Bonventre, J. V., . . . Leslie, C. C. (2014). Serine Hydrolase Inhibitors Block Necrotic Cell Death by Preventing Calcium Overload of the Mitochondria and Permeability Transition Pore Formation. JOURNAL OF BIOLOGICAL CHEMISTRY, 289(3), 1491-1504. doi:10.1074/jbc.M113.497651
Agrawal, P., Kurcon, T., Pilobello, K. T., Rakus, J. F., Koppolu, S., Liu, Z., . . . Mahal, L. K. (2014). Mapping posttranscriptional regulation of the human glycome uncovers microRNA defining the glycocode. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(11), 4338-4343. doi:10.1073/pnas.1321524111
Manna, J. D., Wepy, J. A., Hsu, K. -L., Chang, J. W., Cravatt, B. F., & Marnett, L. J. (2014). Identification of the Major Prostaglandin Glycerol Ester Hydrolase in Human Cancer Cells. JOURNAL OF BIOLOGICAL CHEMISTRY, 289(49), 33741-33753. doi:10.1074/jbc.M114.582353
Inloes, J. M., Hsu, K. -L., Dix, M. M., Viader, A., Masuda, K., Takei, T., . . . Cravatt, B. F. (2014). The hereditary spastic paraplegia-related enzyme DDHD2 is a principal brain triglyceride lipase. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(41), 14924-14929. doi:10.1073/pnas.1413706111
Grim, T. W., Ghosh, S., Hsu, K. -L., Cravatt, B. F., Kinsey, S. G., & Lichtman, A. H. (2014). Combined inhibition of FAAH and COX produces enhanced anti-allodynic effects in mouse neuropathic and inflammatory pain models. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 124, 405-411. doi:10.1016/j.pbb.2014.07.008
Naydenov, A. V., Horne, E. A., Cheah, C. S., Swinney, K., Hsu, K. -L., Cao, J. K., . . . Stella, N. (2014). ABHD6 Blockade Exerts Antiepileptic Activity in PTZ-Induced Seizures and in Spontaneous Seizures in R6/2 Mice. NEURON, 83(2), 361-371. doi:10.1016/j.neuron.2014.06.030
2013
Nagano, J. M. G., Hsu, K. -L., Whitby, L. R., Niphakis, M. J., Speers, A. E., Brown, S. J., . . . Cravatt, B. F. (2013). Selective inhibitors and tailored activity probes for lipoprotein-associated phospholipase A2. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 23(3), 839-843. doi:10.1016/j.bmcl.2012.11.061
Hsu, K. -L., Tsuboi, K., Whitby, L. R., Speers, A. E., Pugh, H., Inloes, J., & Cravatt, B. F. (2013). Development and Optimization of Piperidyl-1,2,3-Triazole Ureas as Selective Chemical Probes of Endocannabinoid Biosynthesis. JOURNAL OF MEDICINAL CHEMISTRY, 56(21), 8257-8269. doi:10.1021/jm400898x
Hsu, K. -L., Tsuboi, K., Chang, J. W., Whitby, L. R., Speers, A. E., Pugh, H., & Cravatt, B. F. (2013). Discovery and Optimization of Piperidyl-1,2,3-Triazole Ureas as Potent, Selective, and in Vivo-Active Inhibitors of α/β-Hydrolase Domain Containing 6 (ABHD6). JOURNAL OF MEDICINAL CHEMISTRY, 56(21), 8270-8279. doi:10.1021/jm400899c
2012
Zuhl, A. M., Mohr, J. T., Bachovchin, D. A., Niessen, S., Hsu, K. -L., Berlin, J. M., . . . Cravatt, B. F. (2012). Competitive Activity-Based Protein Profiling Identifies Aza-β-Lactams as a Versatile Chemotype for Serine Hydrolase Inhibition. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 134(11), 5068-5071. doi:10.1021/ja300799t
Hsu, K. -L., Tsuboi, K., Adibekian, A., Pugh, H., Masuda, K., & Cravatt, B. F. (2012). DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses. NATURE CHEMICAL BIOLOGY, 8(12), 999-1007. doi:10.1038/NCHEMBIO.1105
Adibekian, A., Martin, B. R., Chang, J. W., Hsu, K. -L., Tsuboi, K., Bachovchin, D. A., . . . Cravatt, B. F. (2012). Confirming Target Engagement for Reversible Inhibitors in Vivo by Kinetically Tuned Activity-Based Probes. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 134(25), 10345-10348. doi:10.1021/ja303400u
2011
Adibekian, A., Martin, B. R., Wang, C., Hsu, K. -L., Bachovchin, D. A., Niessen, S., . . . Cravatt, B. F. (2011). Click-generated triazole ureas as ultrapotent in vivo-active serine hydrolase inhibitors. NATURE CHEMICAL BIOLOGY, 7(7), 469-478. doi:10.1038/NCHEMBIO.579
Hsu, K. -L., Pilobello, K., Krishnamoorthy, L., & Mahal, L. K. (2011). Ratiometric Lectin Microarray Analysis of the Mammalian Cell Surface Glycome. BIOLOGICAL MICROARRAYS: METHODS AND PROTOCOLS, 671, 117-131. doi:10.1007/978-1-59745-551-0_6
Propheter, D. C., Hsu, K. -L., & Mahal, L. K. (2011). Recombinant Lectin Microarrays for Glycomic Analysis. PROTEIN MICROARRAY FOR DISEASE ANALYSIS: METHODS AND PROTOCOLS, 723, 67-77. doi:10.1007/978-1-61779-043-0_6
2010
Propheter, D. C., Hsu, K. -L., & Mahal, L. K. (2010). Fabrication of an Oriented Lectin Microarray. CHEMBIOCHEM, 11(9), 1203-1207. doi:10.1002/cbic.201000106