Publications

Key Target and Disease Publications

Insightful discoveries and key experiments from the founder’s labs link Elgia’s proprietary targets to disease intervention and resolution.

ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activation of S1P

Ju Youn Kim, Ricard Garcia-Carbonell, Shinichiro Yamachika, …, Randal J. Kaufman, Alan R. Saltiel. Michael Karin.
Cell. 2018 Sep 20;175(1):133-145.e15. doi: 10.1016/j.cell.2018.08.020. Epub 2018 Sep 13. PMID: 30220454

New mitochondrial DNA synthesis enables NLRP3 inflammasome activation

Zhenyu Zhong, Shuang Liang, Elsa Sanchez-Lopez, Feng He, Shabnam Shalapour, Xue-jia Lin, Jerry Wong, Siyuan Ding, Ekihiro, Seki, Bernd Schnabi, Andrea L. Hevener, Harry B. Greenberg, Tatiana Kisseleva & Michael Karin.
Nature. 2018 Aug;560(7717):198-203. doi: 10.1038/s41586-018-0372-z. Epub 2018 Jul 25. PMID: 30046112 PMCID: PMC6329306

NFκB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria

Zhenyu Zhong ¹, Atsushi Umemura ², Elsa Sanchez-Lopez ¹, Shuang Liang ³, Shabnam Shalapour ¹, Jerry Wong ¹, Feng He ¹, Daniela Boassa ⁴, Guy Perkins ⁴, Syed Raza Ali ⁵, Matthew D McGeough ⁵, Mark H Ellisman ⁴, Ekihiro Seki ⁶, Asa B Gustafsson ⁷, Hal M Hoffman ⁵, Maria T Diaz-Meco ⁸, Jorge Moscat ⁸, Michael Karin ⁹ Cell. 2016 Feb 25;164(5):896-910. doi: 10.1016/j.cell.2015.12.057. PMID: 26919428

Tailoring small molecules for an allosteric site on procaspase-6.

Murray J, Giannetti AM, Steffek M, Gibbons P, Hearn BR, Cohen F, Tam C, Pozniak C, Bravo B, Lewcock J, Jaishankar P, Ly CQ, Zhao X, Tang Y, Chugha P, Arkin MR, Flygare J, Renslo AR.ChemMedChem. 2014 Jan;9(1):73-7, 2. doi: 10.1002/cmdc.201300424. Epub 2013 Nov 20.PMID: 24259468

Structural and enzymatic insights into caspase-2 protein substrate recognition and catalysis.

Tang Y, Wells JA, Arkin MR. J Biol Chem. 2011 Sep 30;286(39):34147-54. doi: 10.1074/jbc.M111.247627. Epub 2011 Aug 2.PMID: 21828056

NLR Family Pyrin Domain-Containing 3 Inflammasome Activation in Hepatic Stellate Cells Induces Liver Fibrosis in Mice.

Inzaugarat ME, Johnson CD, Holtmann TM, McGeough MD, Trautwein C, Papouchado BG, Schwabe R, Hoffman HM, Wree A, Feldstein AE. Hepatology. 2019 Feb;69(2):845-859. doi: 10.1002/hep.30252. Epub 2019 Jan 3.PMID: 30180270 Free PMC article.

Neutrophils contribute to spontaneous resolution of liver inflammation and fibrosis via microRNA-223.

Calvente CJ, Tameda M, Johnson CD, Del Pilar H, Lin YC, Adronikou N, De Mollerat Du Jeu X, Llorente C, Boyer J, Feldstein AE. J Clin Invest. 2019 Jul 11;129(10):4091-4109. doi: 10.1172/JCI122258.PMID: 31295147 Free PMC article.

MicroRNA 223 3p Negatively Regulates the NLRP3 Inflammasome in Acute and Chronic Liver Injury.

Jimenez Calvente C, Del Pilar H, Tameda M, Johnson CD, Feldstein AE. Mol Ther. 2020 Feb 5;28(2):653-663. doi: 10.1016/j.ymthe.2019.09.013. Epub 2019 Sep 13.PMID: 31585800

The Power of Single Cell Analysis for the Study of Liver Pathobiology.

Chu AL, Schilling JD, King KR, Feldstein AE. Hepatology. 2020 Aug 1. doi: 10.1002/hep.31485. Online ahead of print.PMID: 32740968 Review.

Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis.

Gaul S, Leszczynska A, Alegre F, Kaufmann B, Johnson CD, Adams LA, Wree A, Damm G, Seehofer D, Calvente CJ, Povero D, Kisseleva T, Eguchi A, McGeough MD, Hoffman HM, Pelegrin P, Laufs U,Feldstein AE. J Hepatol. 2020 Aug 4:S0168-8278(20)30522-5. doi: 10.1016/j.jhep.2020.07.041. Online ahead of print.PMID: 32763266

An AMPK-caspase-6 axis controls liver damage in nonalcoholic steatohepatitis.

Zhao P, Sun X, Chaggan C, Liao Z, In Wong K, He F, Singh S, Loomba R, Karin M, Witztum JL, Saltiel AR. Science. 2020 Feb 7;367(6478):652-660. doi: 10.1126/science.aay0542. PMID: 32029622

From overnutrition to liver injury: AMP-activated protein kinase in nonalcoholic fatty liver diseases.

Zhao P, Saltiel AR. J Biol Chem. 2020 Aug 21;295(34):12279-12289. doi: 10.1074/jbc.REV120.011356. Epub 2020 Jul 10. PMID: 32651233

TANK-Binding Kinase 1 Regulates the Localization of Acyl-CoA Synthetase ACSL1 to Control Hepatic Fatty Acid Oxidation.

Huh JY, Reilly SM, Abu-Odeh M, Murphy AN, Mahata SK, Zhang J, Cho Y, Seo JB, Hung CW, Green CR, Metallo CM, Saltiel AR. Cell Metab. 2020 Oct 26:S1550-4131(20)30543-X. doi: 10.1016/j.cmet.2020.10.010. Online ahead of print. PMID: 33152322

Design, synthesis, and biological activity of substituted 2-amino-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxylic acid derivatives as inhibitors of the inflammatory kinases TBK1 and IKKε for the treatment of obesity.

Beyett TS, Gan X, Reilly SM, Gomez AV, Chang L, Tesmer JJG, Saltiel AR, Showalter HD. Bioorg Med Chem. 2018 Nov 1;26(20):5443-5461. doi: 10.1016/j.bmc.2018.09.020. Epub 2018 Sep 20. PMID: 30270002

TBK1 at the Crossroads of Inflammation and Energy Homeostasis in Adipose Tissue.

Zhao P, Wong KI, Sun X, Reilly SM, Uhm M, Liao Z, Skorobogatko Y, Saltiel AR. Cell. 2018 Feb 8;172(4):731-743.e12. doi: 10.1016/j.cell.2018.01.007. PMID: 29425491

Inhibition of IKKɛ and TBK1 Improves Glucose Control in a Subset of Patients with Type 2 Diabetes.

Oral EA, Reilly SM, Gomez AV, Meral R, Butz L, Ajluni N, Chenevert TL, Korytnaya E, Neidert AH, Hench R, Rus D, Horowitz JF, Poirier B, Zhao P, Lehmann K, Jain M, Yu R, Liddle C, Ahmadian M, Downes M, Evans RM, Saltiel AR.Cell Metab. 2017 Jul 5;26(1):157-170.e7. doi: 10.1016/j.cmet.2017.06.006. PMID: 28683283