Dale Hoyt's lab is interested in endothelial cell injury, dysfunction, and death. As endothelial cells line the inside of all blood vessels, damage to them impairs the normal operation of the circulatory system and leads to life-threatening diseases. Pulmonary fibrosis and atherosclerosis are examples. Conversely, endothelium in the tumor vasculature is a potentially important target for antitumor therapy. One of the lab's goals is to develop drugs to manipulate the sensitivity of endothelium to DNA damaging agents, including oxidants, in order to inhibit endothelial injury in normal tissue, or to enhance it in cancer. As an example, engagement of integrin cell adhesion receptors inhibits endothelial DNA breakage and cell death caused by several unrelated types of agents. We are investigating how nuclear structure is altered by integrins, and the signal transduction paths that are activated. We are also interested in the phosphorylation signals that affect vascular stress responses and cancer.
- MS, PhD, Oregon State University
- BA, Humboldt State University
Pan CC, Shah N, Kumar S, Wheeler SE, Cinti J, Hoyt DG, Beattie CE, An M, Mythreye K, Rakotondraibe LH, Lee NY. Angiostatic actions of capsicodendrin through selective inhibition of VEGFR2-mediated AKT signaling and disregulated autophagy. Oncotarget. 2017 Feb 21;8(8):12675-12685. doi: 10.18632/oncotarget.9307. PMID: 27177332; PMCID: PMC5355044.
Pan CC, Kumar S, Shah N, Bloodworth JC, Hawinkels LJ, Mythreye K, Hoyt DG, Lee NY. Endoglin Regulation of Smad2 Function Mediates Beclin1 Expression and Endothelial Autophagy. J Biol Chem. 2015 Jun 12;290(24):14884-92. doi: 10.1074/jbc.M114.630178. Epub 2015 Apr 30. PMID: 25931117; PMCID: PMC4463436.
Liu T, Schneider RA, Lee NY, Hoyt DG. Peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1) regulates pulmonary effects of endotoxin and tumor necrosis factor-α in mice. Biochem Biophys Res Commun. 2014 Sep 26;452(3):468-72. doi: 10.1016/j.bbrc.2014.08.089. Epub 2014 Aug 23. PMID: 25159840.
Pan CC, Kumar S, Shah N, Hoyt DG, Hawinkels LJ, Mythreye K, Lee NY. Src- mediated post-translational regulation of endoglin stability and function is critical for angiogenesis. J Biol Chem. 2014 Sep 12;289(37):25486-96. doi: 10.1074/jbc.M114.578609. Epub 2014 Jul 28. PMID: 25070888; PMCID: PMC4162155.
Liu T, Schneider RA, Hoyt DG. Calpastatin is regulated by protein never in mitosis gene A interacting-1 (PIN1) in endothelial cells. Biochem Biophys Res Commun. 2011 Oct 28;414(3):581-6. doi: 10.1016/j.bbrc.2011.09.125. Epub 2011 Oct 1. PMID: 21982763.
Lin L, Deangelis S, Foust E, Fuchs J, Li C, Li PK, Schwartz EB, Lesinski GB, Benson D, Lü J, Hoyt D, Lin J. A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells. Mol Cancer. 2010 Aug 16;9:217. doi: 10.1186/1476-4598-9-217. PMID: 20712901; PMCID: PMC2936338.
Bill MA, Fuchs JR, Li C, Yui J, Bakan C, Benson DM Jr, Schwartz EB, Abdelhamid D, Lin J, Hoyt DG, Fossey SL, Young GS, Carson WE 3rd, Li PK, Lesinski GB. The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity. Mol Cancer. 2010 Jun 25;9:165. doi: 10.1186/1476-4598-9-165. PMID: 20576164; PMCID: PMC2902420.
Liu T, Schneider RA, Shah V, Huang Y, Likhotvorik RI, Keshvara L, Hoyt DG. Protein Never in Mitosis Gene A Interacting-1 regulates calpain activity and the degradation of cyclooxygenase-2 in endothelial cells. J Inflamm (Lond). 2009 Jun 22;6:20. doi: 10.1186/1476-9255-6-20. PMID: 19545424; PMCID: PMC2708161.
Liu T, Huang Y, Likhotvorik RI, Keshvara L, Hoyt DG. Protein Never in Mitosis Gene A Interacting-1 (PIN1) regulates degradation of inducible nitric oxide synthase in endothelial cells. Am J Physiol Cell Physiol. 2008 Sep;295(3):C819-27. doi: 10.1152/ajpcell.00366.2007. Epub 2008 Jul 23. PMID: 18650263.
Huang H, Liu T, Rose JL, Stevens RL, Hoyt DG. Sensitivity of mice to lipopolysaccharide is increased by a high saturated fat and cholesterol diet. J Inflamm (Lond). 2007 Nov 12;4:22. doi: 10.1186/1476-9255-4-22. PMID: 17997851; PMCID: PMC2186306.