Lagace, Thomas

Sommaire 

Thomas Lagace est un scientifique et un directeur de Laboratoire de biologie des récepteurs des lipoprotéines à l’Institut de cardiologie de l’Université d’Ottawa(ICUO) et professeur adjoint au Département de pathologie et médecine de laboratoire de l’Université d’Ottawa.

Parcours 

Thomas Lagace a obtenu en 2004 un doctorat en biochimie et biologie moléculaire de l’Université Dalhousie, à Halifax; ses travaux ont porté sur l’étude du métabolisme cellulaire du cholestérol et des phospholipides. Grâce à des bourses postdoctorales du Conseil de recherches en sciences naturelles et en génie du Canada et des Instituts de recherche en santé du Canada, il a passé quatre années au Département de génétique moléculaire du Centre médical Southwestern de l’Université du Texas, à Dallas. Durant cette période, Thomas Lagacé a joué un rôle majeur dans plusieurs découvertes sur l’action de la sérine protéase PCSK9, un régulateur du taux plasmatique des lipoprotéines de faible densité nouvellement détecté, que l’on considère comme un facteur de risque de maladie du cœur.

Thomas Lagace occupe son poste à l’Institut de cardiologie depuis janvier 2009. Des subventions de fonctionnement des IRSC, du CRNSG et de la Fondation des maladies du cœur du Canada permettent à son laboratoire de recherche de poursuivre ses travaux sur la régulation des taux de cholestérol circulants.

Intérêts cliniques et de recherche 

Thomas Lagace s’intéresse principalement aux mécanismes cellulaires et moléculaires qui régissent l’homéostasie du cholestérol et les taux de lipoprotéines plasmatiques, et en particulier aux interactions entre les récepteurs de lipoprotéines à la surface des cellules et leurs ligands.

Publications 

Voir la liste des publications actuelles sur PubMed.

Publications choisies:

  • My-Anh Nguyen, Tanja Kosenko and Thomas A. Lagace (2014) Internalized PCSK9 Dissociates from Recycling LDL Receptors in PCSK9-Resistant SV-589 Fibroblasts. The Journal of Lipid Research. 55, pp. 266-275.
  • Thomas A. Lagace and Neale D. Ridgway (2013) The role of phospholipids in the biological activity and structure of the endoplasmic reticulum. Biochim Biophys Acta – Molecular Cell Research 1833(11), pp. 2499-2510.
  • Tanja Kosenko, Mia Golder, Geoffrey Leblond, Willie Weng, and Thomas A. Lagace (2013) Low-Density Lipoprotein Binds to Proprotein Convertase Subtilisin/Kexin Type-9 (PCSK9) in Human Plasma and Inhibits PCSK9-Mediated LDL Receptor Degradation. The Journal of Biological Chemistry 288:8279-8288.
  • Susan G. Lakoski, Thomas A. Lagace, Jonathan C. Cohen, Jay D. Horton, and Helen H. Hobbs (2009) Plasma levels of PCSK9 in a large multiethnic population. The Journal of Clinical Endocrinology and Metabolism 94(7), pp. 2537-2543.
  • Thomas A. Lagace (2009) PCSK9 and heart disease: quieting an outdated metabolic moderator. Clinical Lipidology 4(4), pp. 407-410.
  • Markey C. McNutt, Hyock Joo Kwon, Chiyuan Chen, Justin R. Chen, Jay D. Horton and Thomas A. Lagace (2009) Antagonism of Secreted PCSK9 Increases Low-Density Lipoprotein Receptor Expression in HepG2 Cells. The Journal of Biological Chemistry. 284, pp. 10561-10570.
  • Hyock Joo Kwon, Thomas A. Lagace, Markey C. McNutt, Jay D. Horton, and Johann Deisenhofer (2008) Molecular basis for LDL receptor recognition by PCSK9. Proc. Nat. Acad. Sci. 105, pp.1820-1825.
  • Markey C. McNutt, Thomas A. Lagace, and Jay D. Horton (2007) Catalytic Activity is Not Required for Secreted PCSK9 to Reduce LDL Receptors in HepG2 Cells. J. Biol. Chem. 282, pp. 20799-20803.
  • Thomas A. Lagace, David E. Curtis, Rita Garuti, Markey C. McNutt, Sahng Wook Park, Heidi B. Prather, Norma N. Anderson, Y. K. Ho, Robert E. Hammer, and Jay D. Horton (2006) Secreted PCSK9 Decreases LDL Receptors in Hepatocytes and in Livers of Parabiotic Mice. J. Clin. Invest. 116(11) pp. 2995-3005.

LISTE COMPLETE DES ARTICLES PARUS DANS DES REVUES SCIENTIFIQUES

  • My-Anh Nguyen, Tanja Kosenko and Thomas A. Lagace (2014) Internalized PCSK9 Dissociates from Recycling LDL Receptors in PCSK9-Resistant SV-589 Fibroblasts. The Journal of Lipid Research. 55, pp. 266-275.
  • Thomas A. Lagace and Neale D. Ridgway (2013) The role of phospholipids in the biological activity and structure of the endoplasmic reticulum. Biochim Biophys Acta – Molecular Cell Research 1833(11), pp. 2499-2510.
  • Tanja Kosenko, Mia Golder, Geoffrey Leblond, Willie Weng, and Thomas A. Lagace (2013) Low-Density Lipoprotein Binds to Proprotein Convertase Subtilisin/Kexin Type-9 (PCSK9) in Human Plasma and Inhibits PCSK9-Mediated LDL Receptor Degradation. The Journal of Biological Chemistry 288:8279-8288.
  • Susan G. Lakoski, Thomas A. Lagace, Jonathan C. Cohen, Jay D. Horton, and Helen H. Hobbs (2009) Plasma levels of PCSK9 in a large multiethnic population. The Journal of Clinical Endocrinology and Metabolism 94(7), pp. 2537-2543.
  • Thomas A. Lagace (2009) PCSK9 and heart disease: quieting an outdated metabolic moderator. Clinical Lipidology 4(4), pp. 407-410.
  • Markey C. McNutt, Hyock Joo Kwon, Chiyuan Chen, Justin R. Chen, Jay D. Horton and Thomas A. Lagace (2009) Antagonism of Secreted PCSK9 Increases Low-Density Lipoprotein Receptor Expression in HepG2 Cells. The Journal of Biological Chemistry. 284, pp. 10561-10570.
  • Hyock Joo Kwon, Thomas A. Lagace, Markey C. McNutt, Jay D. Horton, and Johann Deisenhofer (2008) Molecular basis for LDL receptor recognition by PCSK9. Proc. Nat. Acad. Sci. 105, pp.1820-1825.
  • Markey C. McNutt, Thomas A. Lagace, and Jay D. Horton (2007) Catalytic Activity is Not Required for Secreted PCSK9 to Reduce LDL Receptors in HepG2 Cells. J. Biol. Chem. 282, pp. 20799-20803.
  • Thomas A. Lagace, David E. Curtis, Rita Garuti, Markey C. McNutt, Sahng Wook Park, Heidi B. Prather, Norma N. Anderson, Y. K. Ho, Robert E. Hammer, and Jay D. Horton (2006) Secreted PCSK9 Decreases LDL Receptors in Hepatocytes and in Livers of Parabiotic Mice. J. Clin. Invest. 116(11) pp. 2995-3005.
  • McNutt MC, Kwon HJ, Chen C, Chen JR, Horton JD, Lagace TA. Antagonism of secreted PCSK9 increases low-density lipoprotein receptor expression in hepG2 cells. J Biol Chem 2009 (in press).
  • Gehrig K, Lagace TA, Ridgway ND. Oxysterol activation of phosphatidylcholine synthesis involves CTP: phosphocholine cytidylyltransferase alpha translocation to the nuclear envelope. Biochem J 2009;418(1):209-217.
  • Grefhorst A, McNutt MC, Lagace TA, Horton JD. Plasma PCSK9 functions to preferentially reduce liver LDL receptors in mice. J Lipid Res 2008;49:1303-1311.
  • Kwon HJ, Lagace TA, McNutt MC, Horton JD, Deisenhofer J. Molecular basis for LDL receptor recognition by PCSK9. Proc Nat Acad Sci 2008;105:1820-1825.
  • McNutt MC, Lagace TA, Horton JD. Catalytic activity is not required for secreted PCSK9 to reduce LDL receptors in hepG2 Cells. J Biol Che 2007;282:20799-20803.
  • Markey C. McNutt, Hyock Joo Kwon, Chiyuan Chen, Justin R. Chen, Jay D. Horton and Thomas A. Lagace (2009) Antagonism of Secreted PCSK9 Increases Low-Density Lipoprotein Receptor Expression in HepG2 Cells. J. Biol. Chem. (in press).
  • Karsten Gehrig, Thomas A. Lagace and Neale D. Ridgway (2009) Oxysterol activation of phosphatidylcholine synthesis involves CTP:phosphocholine cytidylyltransferase alpha translocation to the nuclear envelope. Biochem. J. 418(1) pp.209-217.
  • Aldo Grefhorst, Markey C. McNutt, Thomas A. Lagace, and Jay D. Horton (2008) Plasma PCSK9 Functions to Preferentially Reduce Liver LDL Receptors in Mice. J. Lipid Res. 49, pp. 1303-1311.
  • Hyock Joo Kwon, Thomas A. Lagace, Markey C. McNutt, Jay D. Horton, and Johann Deisenhofer (2008) Molecular basis for LDL receptor recognition by PCSK9. Proc. Nat. Acad. Sci. 105, pp.1820-1825.
  • Markey C. McNutt, Thomas A. Lagace, and Jay D. Horton (2007) Catalytic Activity is Not Required for Secreted PCSK9 to Reduce LDL Receptors in HepG2 Cells. J. Biol. Chem. 282, pp. 20799-20803.
  • Da-Wei Zhang, Thomas A. Lagace, Rita Garuti, Zhenze Zhao, Meghan McDonald, Jay D. Horton, Jonathan C. Cohen and Helen H. Hobbs (2007) Binding of Proprotein Convertase Subtilisin/Kexin Type 9 to Epidermal Growth Factor-like Repeat A of Low Density Lipoprotein Receptor Decreases Receptor Recycling and Increases Degradation. J. Biol. Chem. 282, pp. 18602-18612.
  • Thomas A. Lagace, David E. Curtis, Rita Garuti, Markey C. McNutt, Sahng Wook Park, Heidi B. Prather, Norma N. Anderson, Y. K. Ho, Robert E. Hammer, and Jay D. Horton (2006) Secreted PCSK9 Decreases LDL Receptors in Hepatocytes and in Livers of Parabiotic Mice. J. Clin. Invest. 116(11) pp. 2995-3005.
  • Zhenze Zhao, Yetsa Tuakli-Wosornu, Thomas A. Lagace, Lisa Kinch, Nicholas V. Grishin, Jay D. Horton, Jonathan C. Cohen, and Helen H. Hobbs (2006) Molecular Characterization of Loss-of-Function Mutations in PCSK9 and Identification of a Compound Heterozygote. Am. J. Hum. Genet. 73(9) pp. 514-523.
  • Thomas A. Lagace and Neale D. Ridgway (2005) Induction of apoptosis by lipophilic activators of CTP:phosphocholine cytidylyltransferase alpha (CCTalpha). Biochem. J. 392(3) pp.449-456.
  • Thomas A. Lagace and Neale D. Ridgway (2005) The Rate-limiting Enzyme in Phosphatidylcholine Synthesis Regulates Proliferation of the Nucleoplasmic Reticulum. Mol. Biol. Cell 16(3) pp.1120-1130.
  • Neale D. Ridgway and Thomas A. Lagace (2003) Regulation of the CDP-choline pathway by sterol regulatory element binding proteins involves transcriptional and post-transcriptional mechanisms. Biochem. J. 15;372(Pt. 3) pp. 811-819.
  • Thomas A. Lagace, Jessica R. Miller, and Neale D. Ridgway (2002) Caspase Processing and Nuclear Export of CTP:Phosphocholine Cytidylyltransferase ï�¡ during Farnesol-Induced Apoptosis. Mol. Cell. Biol. 22, pp. 4851-4862.
  • Marcia M. Wright, Annette L. Henneberry, Thomas A. Lagace, Neale D. Ridgway, and Christopher R. McMaster (2001) Uncoupling Farnesol Induced Apoptosis From its Inhibition of Phosphatidylcholine Synthesis. J. Biol. Chem. 276, pp. 25254-25261.
  • Annette L. Henneberry, Thomas A. Lagace, Neale D. Ridgway and Christopher R. McMaster (2001) Phosphatidylcholine Synthesis Influences the Diacylglycerol Homeostasis Required for Sec14p-dependent Golgi Function and Cell Growth. Mol. Biol. Cell 12, pp. 511-520.
  • Thomas A. Lagace, Margo K. Storey, and Neale D. Ridgway (2000) Regulation of Phosphatidylcholine Metabolism in Chinese Hamster Ovary Cells by the Sterol Regulatory Element-binding Protein (SREBP)/SREBP Cleavage-activating Protein Pathway. J. Biol. Chem. 275, pp. 14367-14374.
  • Thomas A. Lagace, David M. Byers, Harold W. Cook, and Neale D. Ridgway (1999) Chinese hamster ovary cells overexpressing the oxysterol binding protein (OSBP) display enhanced synthesis of sphingomyelin in response to 25-hydroxycholesterol. J. Lipid Res. 40, pp. 109-116.
  • Neale D. Ridgway, Thomas A. Lagace, Harold W. Cook, and David M. Byers (1998) Differential Effects of Sphingomyelin Hydrolysis and Cholesterol Transport on Oxysterol-binding Protein Phosphorylation and Golgi Localization. J. Biol. Chem. 273, pp. 31621-31628.
  • Thomas A. Lagace, David M. Byers, Harold W. Cook, and Neale D. Ridgway (1997) Altered regulation of cholesterol and cholesteryl ester synthesis in Chinese hamster ovary cells overexpressing the oxysterol-binding protein is dependent on the pleckstrin homology domain. Biochem. J. 326, pp. 205-213.
  • Neale D. Ridgway and Thomas A. Lagace (1995) Brefeldin A Renders Chinese Hamster Ovary Cells Insensitive to Transcriptional Suppression by 25-Hydroxycholesterol. J. Biol. Chem. 270, pp. 8023-8031.

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