The Gavathiotis laboratory aims to investigate and target mechanisms of protein-protein interactions in cell death and cell survival signaling, which are deregulated in cancer and other diseases. In this effort, we develop novel pharmacological strategies and chemical probes that can be used for target validation and serve as the basis for novel therapeutics. By operating at the interface of chemistry and biology, and developing innovative approaches, our goal is to advance our understanding of biological processes and provide new opportunities for drug discovery and development. To achieve our goal, we take an interdisciplinary approach using chemical synthesis, structure-based design, structural biology (NMR and X-ray crystallography), biochemistry, cellular and in vivo pharmacology.
Gavathiotis E. and Walensky LD. Tracking BAX once the Trigger is Pulled. Cell Cycle 2011, 10:868-870.
Walensky LD. and Gavathiotis E*. BAX Unleashed: The Biochemical Transformation of an Inactive Cytosolic Monomer into a Toxic Mitochondrial Pore. Trends Biochem. Sci. 2011, 36:642:652
Whelan RS, Konstantinidis K, Wei AC, Chen Y, Reyna DE, Jha S, Yang Y, Calvert JW, Lindsten T, Thompson CB, Crow MT, Gavathiotis E, Dorn GW 2nd, O'Rourke B, Kitsis RN. Bax regulates primary necrosis through mitochondrial dynamics. Proc Natl Acad Sci U S A. 2012, 109:6566-6571.
LaBelle JL, Katz SK, Bird GH, Gavathiotis E, Stewart ML, Lawrence C, Fisher JK, Godes M, Pitter K, Kung AL, Walensky LD. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers. J. Clin. Invest. 2012, 122:2018-2031.
Gavathiotis E*, Reyna DE, Bellairs JA, Leshchiner ES, Walensky LD. Direct and selective small-molecule activation of proapoptotic BAX. Nature Chem. Bio. 2012, 8:639-645.
Cohen NA, Stewart ML, Gavathiotis E, Tepper JL, Opferman JT, Walensky LD. A competitive stapled peptide screen identified a selective small molecule that overcomes MCL-1 dependent leukemia cell survival. Chem & Biol. 2012, 19: 1175-1186.
Li R, Cheng C, Balasis ME, Liu Y, Garner TP, Daniel KG, Li J, Qin Y, Gavathiotis E*, Sebti SM. Design, synthesis and evaluation of Marinopyrrole derivatives as selective inhibitors of Mcl-1 binding to pro-apoptotic Bim and dual Mcl-1/Bcl-xL inhibitors.Eur. J. Med. Chem. 2015, 90: 315-331
Barclay LA, Wales TE, Garner TP, Wachter F, Lee S, Guerra R, Stewart ML, Braun CR, Bird GH, Gavathiotis E, Engen JR, Walensky LD. Inhibition of Pro-apoptotic BAX by a noncanonical interaction mechanism. Mol. Cell 2015, 57: 1-14.
Chen HC, Kanai M, Inoue-Yamauchi A, Tu HC, Huang Y, Ren D, Kim H, Takeda S, Reyna DE, Chan PM, Ganesan YT, Liao CP, Gavathiotis E, Hsieh JJ, Cheng EH. An interconnected hierarchical model of cell death regulation by the BCL-2 family. Nat Cell Biol. 2015, 17: 1270-1281.
Uchime O, Dai Z, Biris N, Lee D, Sidhu SS, Li S, Lai JR, Gavathiotis E. Synthetic Antibodies Inhibit Bcl-2-associated X Protein (BAX) through Blockade of the N-terminal Activation Site. J. Biol. Chem. 2015, 291: 89-102.
Klionsky DJ, ..., Gavathiotis E, ...Zughaier SM. Guidelines for the use and intepretation of assays for monitoring autophagy. Autophagy. 2016, 12: 1-222.
Cotto-Rios XM, Gavathiotis E. Unraveling cell death mysteries. Nat. Chem. Biol. 2016 12: 470-471
Garner TP, Reyna DE, Priyadarshi A, Chen HC, Li S, Ganesan, YT, Malashkevich VN, Almo SS, Cheng EH, Gavathiotis E. An Autoinhibited Dimeric Form of BAX Regulates the BAX Activation Pathway. Mol. Cell 2016, 63: 485-497.
Karoulia Z, Wu Y, Ahmed AA, Xin Q, Bollard J, Krepler C, Wu X, Zhang C, Bollag G, Herlyn M, Fagin JA, Lujambio A, Gavathiotis E*, Poulikakos P. An Integrated Model of RAF inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling. Cancer Cell 2016, 30: 1-14.
Reyna DE and Gavathiotis E. Self-regulation of BAX-induced cell death. Oncotarget 2016
Johnson JL, Ramadass M, He J, Brown SJ, Zhang J, Abgaryan L, Biris N, Gavathiotis E, Rosen H, Catz SD. Identification of Nexinhibs, small-molecule inhibitors of neutrophil exocytosis and inflammation. Druggability of the small GTPase Rab27a. J. Biol. Chem. 2016 jbc.M116.741884
*denotes co-corresponding author
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More Information About Dr. Evripidis Gavathiotis
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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Golding Building, Room G01D
Bronx, NY 10461