Dale Hoyt

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photo of Dale Hoyt

Dale Hoyt, PhD

Title
Associate Professor
Unit / Department / Division
Pharmaceutics and Pharmacology
Address
406 Riffe Building
Email Address
Phone Number

Professional Interests

Professional Interests

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.

Education

  • MS, PhD, Oregon State University
  • BA, Humboldt State University

Journal Articles

  • Newell, B.W.; Spaulding, A.M.; Lee, N.Y.; Hoyt, D.G. Roscovitine inhibits endotoxin-induced lung inflammation in mice lacking peptidylprolyl cis/trans isomerase, NIMAinteracting 1 (PIN1) Pulmonary and Critical Care Medicine. 2016 Jul; 1(3):63-66.
  • Pan, C.C.; Shah, N.; Kumar, S.; Wheeler, S.E. et al. Angiostatic actions of capsicodendrin through selective inhibition of VEGFR2-mediated AKT signaling and disregulated autophagy Oncotarget. 2016 May; 21;8(8):12675-12685.
  • Pan, C.C.; Kumar, S.; Shah, N.; Bloodworth, J.C. et al. Endoglin Regulation of Smad2 Function Mediates Beclin1 Expression and Endothelial Autophagy. J Biol Chem. 2015 Jun; 290(24):14884-14892.
  • Liu, T.; Schneider, R.A.; Lee, N.Y.; Hoyt, D.G. 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; 452(3):468-472.
  • Pan, C.C.; Kumar, S.; Shah, N.; Hoyt, D.G. et al. Src-mediated post-translational regulation of endoglin stability and function is critical for angiogenesis. J Biol Chem. 2014 Sep; 289(37):25486-25496.
  • Kumar, S.; Pan, C.C.; Bloodworth, J.C.; Nixon, A.B. et al. Antibody-directed coupling of endoglin and MMP-14 is a key mechanism for endoglin shedding and deregulation of TGF-β signaling. Oncogene. 2014 Jul; 33(30):3970-3979.
  • Liu, T.; Schneider, R.A.; Hoyt, D.G. Calpastatin is regulated by protein never in mitosis gene A interacting-1 (PIN1) in endothelial cells. Biochem Biophys Res Commun. 2011 Oct; 414(3):581-586.
  • Lin, L.; Deangelis, S.; Foust, E.; Fuchs, J. et al. 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; 9 217.
  • Bill, M.A.; Fuchs, J.R.; Li, C.; Yui, J. et al. 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; 9 165.
  • Liu, T.; Schneider, R.A.; Shah, V.; Huang, Y. et al. 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; 6 20.
  • Liu, T.; Huang, Y.; Likhotvorik, R.I.; Keshvara, L. et al. 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-C827.
  • Huang, H.; Liu, T.; Rose, J.L.; Stevens, R.L. et al. Sensitivity of mice to lipopolysaccharide is increased by a high saturated fat and cholesterol diet. J Inflamm (Lond). 2007 Nov; 4 22.
  • Rose, J.L.; Reeves, K.C.; Likhotvorik, R.I.; Hoyt, D.G. Base excision repair proteins are required for integrin-mediated suppression of bleomycin-induced DNA breakage in murine lung endothelial cells. J Pharmacol Exp Ther. 2007 Apr; 321(1):318-326.
  • Hoyt, D.G.; Knoell, D. Respiratory pharmacology. In defense of the lung: innovations to bolster or prevent acute and chronic lung diseases Current Opinion in Pharmacology. 2006 Jun; 6(3):227-229.
  • Wei, X.; Dai, G.; Marcucci, G.; Liu, Z. et al. A specific picomolar hybridization-based ELISA assay for the determination of phosphorothioate oligonucleotides in plasma and cellular matrices. Pharm Res. 2006 Jun; 23(6):1251-1264.
  • Rose, J.L.; Huang, H.; Wray, S.F.; Hoyt, D.G. Integrin engagement increases histone H3 acetylation and reduces histone H1 association with DNA in murine lung endothelial cells. Mol Pharmacol. 2005 Aug; 68(2):439-446.
  • Dai, G.; Chan, K.K.; Liu, S.; Hoyt, D. et al. Cellular uptake and intracellular levels of the bcl-2 antisense g3139 in cultured cells and treated patients with acute myeloid leukemia. Clin Cancer Res. 2005 Apr; 11(8):2998-3008.
  • Huang, H.; Rose, J.L.; Hoyt, D.G. p38 Mitogen-activated protein kinase mediates synergistic induction of inducible nitric-oxide synthase by lipopolysaccharide and interferon-gamma through signal transducer and activator of transcription 1 Ser727 phosphorylation in murine aortic endothelial cells. Mol Pharmacol. 2004 Aug; 66(2):302-311.
  • Baliga, R.S.; Liu, C.; Hoyt, D.G.; Chaves, A.A. et al. Vascular endothelial toxicity induced by HIV protease inhibitor: evidence of oxidant-related dysfunction and apoptosis. Cardiovasc Toxicol. 2004 Jan; 4(2):199-206.
  • Huang, H.; McIntosh, J.L.; Fang, L.; Szabo, C. et al. Integrin-mediated suppression of endotoxin-induced DNA damage in lung endothelial cells is sensitive to poly(ADP-ribose) polymerase-1 gene deletion. Int J Mol Med. 2003 Oct; 12(4):533-540.
  • Mihm, M.J.; Wattanapitayakul, S.K.; Piao, S-F.; Hoyt, D.G. et al. Effects of angiotensin II on vascular endothelial cells: formation of receptor-mediated reactive nitrogen species. Biochem Pharmacol. 2003 Apr; 65(7):1189-1197.
  • Huang, H.; McIntosh, J.; Hoyt, D.G. An efficient, nonenzymatic method for isolation and culture of murine aortic endothelial cells and their response to inflammatory stimuli. In Vitro Cell Dev Biol Anim. 2003 Jan; 39(1-2):43-50.
  • Jagtap, P.; Soriano, F.G.; Virág, L.; Liaudet, L. et al. Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose) synthetase: potent cytoprotective and antishock agents. Crit Care Med. 2002 May; 30(5):1071-1082.
  • Garcia Soriano F, ; Virág, L.; Jagtap, P.; Szabó, E. et al. Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat Med. 2001 Jan; 7(1):108-113.
  • Jones, C.B.; McIntosh, J.; Huang, H.; Graytock, A. et al. Regulation of bleomycin-induced DNA breakage and chromatin structure in lung endothelial cells by integrins and poly(ADP-ribose) polymerase. Mol Pharmacol. 2001 Jan; 59(1):69-75.
  • Schwartz, D.R.; Homanics, G.E.; Hoyt, D.G.; Klein, E. et al. The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance. Proc Natl Acad Sci U S A. 1999 Apr; 96(8):4680-4685.
  • Ceneviva, G.D.; Tzeng, E.; Hoyt, D.G.; Yee, E. et al. Nitric oxide inhibits lipopolysaccharide-induced apoptosis in pulmonary artery endothelial cells. Am J Physiol. 1998 Oct; 275(4):L717-L728.
  • Hoyt, D.G.; Rizzo, M.; Gerritsen, M.E.; Pitt, B.R. et al. Integrin activation protects pulmonary endothelial cells from the genotoxic effects of bleomycin. Am J Physiol. 1997 Sep; 273(3 Pt 1):L612-L617.
  • Kondo, Y.; Rusnak, J.M.; Hoyt, D.G.; Settineri, C.E. et al. Enhanced apoptosis in metallothionein null cells. Mol Pharmacol. 1997 Aug; 52(2):195-201.
  • Hoyt, D.G.; Rusnak, J.M.; Mannix, R.J.; Modzelewski, R.A. et al. Integrin activation suppresses etoposide-induced DNA strand breakage in cultured murine tumor-derived endothelial cells. Cancer Res. 1996 Sep; 56(18):4146-4149.
  • Woo, E.S.; Kondo, Y.; Watkins, S.C.; Hoyt, D.G. et al. Nucleophilic distribution of metallothionein in human tumor cells. Exp Cell Res. 1996 May; 224(2):365-371.
  • Hoyt, D.G.; Mannix, R.J.; Gerritsen, M.E.; Watkins, S.C. et al. Integrins inhibit LPS-induced DNA strand breakage in cultured lung endothelial cells. Am J Physiol. 1996 Apr; 270(4 Pt 1):L689-L694.
  • Rusnak, J.M.; Calmels, T.P.; Hoyt, D.G.; Kondo, Y. et al. Genesis of discrete higher order DNA fragments in apoptotic human prostatic carcinoma cells. Mol Pharmacol. 1996 Feb; 49(2):244-252.
  • Hoyt, D.G.; Mannix, R.J.; Rusnak, J.M.; Pitt, B.R. et al. Collagen is a survival factor against LPS-induced apoptosis in cultured sheep pulmonary artery endothelial cells. Am J Physiol. 1995 Aug; 269(2 Pt 1):L171-L177.
  • Hoyt, D.G.; Mannix, R.J.; Rusnak, J.M.; Pitt, B.R. et al. Collagen is a survival factor against LPS-induced apoptosis in cultured sheep pulmonary artery endothelial cells American Journal of Physiology - Lung Cellular and Molecular Physiology. 1995 Jan; 269(2 13-2):.
  • Hoyt, D.G.; Lazo, J.S. Acute pneumocyte injury, poly(ADP-ribose) polymerase activity, and pyridine nucleotide levels after in vitro exposure of murine lung slices to cyclophosphamide. Biochem Pharmacol. 1994 Nov; 48(9):1757-1765.
  • Hoyt, D.G.; Lazo, J.S. NAD depletion after in vitro exposure of murine lung slices to bleomycin. Biochem Pharmacol. 1993 Nov; 46(10):1819-1824.
  • Hoyt, D.G.; Lazo, J.S. Murine strain differences in acute lung injury and activation of poly(ADP-ribose) polymerase by in vitro exposure of lung slices to bleomycin. Am J Respir Cell Mol Biol. 1992 Dec; 7(6):645-651.
  • Lazo, J.S.; Hoyt, D.G. The molecular basis of interstitial pulmonary fibrosis caused by antineoplastic agents. Cancer Treat Rev. 1990 Sep; 17(2-3):165-167.
  • Hoyt, D.G.; Lazo, J.S. Bleomycin and cyclophosphamide increase pulmonary type IV procollagen mRNA in mice. Am J Physiol. 1990 Aug; 259(2 Pt 1):L47-L52.
  • Lazo, J.S.; Hoyt, D.G.; Sebti, S.M.; Pitt, B.R. Bleomycin: a pharmacologic tool in the study of the pathogenesis of interstitial pulmonary fibrosis. Pharmacol Ther. 1990 Jan; 47(3):347-358.
  • Harrison, J.H.; Hoyt, D.G.; Lazo, J.S. Acute pulmonary toxicity of bleomycin: DNA scission and matrix protein mRNA levels in bleomycin-sensitive and -resistant strains of mice. Mol Pharmacol. 1989 Aug; 36(2):231-238.
  • Hoyt, D.G.; Lazo, J.S. Early increases in pulmonary mRNA encoding procollagens and transforming growth factor-beta in mice sensitive to cyclophosphamide-induced pulmonary fibrosis. J Pharmacol Exp Ther. 1989 Apr; 249(1):38-43.
  • Hoyt, D.G.; Lazo, J.S. Alterations in pulmonary mRNA encoding procollagens, fibronectin and transforming growth factor-beta precede bleomycin-induced pulmonary fibrosis in mice. J Pharmacol Exp Ther. 1988 Aug; 246(2):765-771.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Bill MA, Fuchs JR, Li C, Yui J, Bakan C, Benson DM, Schwartz EB, Abdelhamid D, Lin J, Hoyt DG, Fossey SL, Young GS, Carson WE, 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.
  • 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.
  • 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.
  • 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.
  • Rose JL, Reeves KC, Likhotvorik RI, Hoyt DG. Base excision repair proteins are required for integrin-mediated suppression of bleomycin-induced DNA breakage in murine lung endothelial cells. J Pharmacol Exp Ther. 2007 Apr;321(1):318-26.