Thomas Lagace directs the Lipoprotein Receptor Biology Laboratory at the University of Ottawa Heart Institute and is Assistant Professor in the Department of Pathology and Laboratory Medicine, at the University of Ottawa.
Background
Dr. Lagace earned his PhD in Biochemistry and Molecular Biology in 2004 studying cellular cholesterol and phospholipid metabolism at Dalhousie University in Halifax. With the support of post-doctoral fellowships from the Natural Sciences and Engineering Research Council and the Canadian Institutes of Health Research, he spent four years in the Department of Molecular Genetics at the University of Texas Southwestern Medical Center in Dallas. During this time, he played a major role in discoveries into the action of the secreted serine protease PCSK9, a newly identified regulator of plasma low-density lipoprotein levels and cardiovascular heart disease risk.
Dr. Lagace took up his current position at the Heart Institute in January 2009. His laboratory research is focused on the regulation of circulating cholesterol levels with the support of operating grants from the CIHR, NSERC and the Heart and Stroke Foundation of Canada.
Research and clinical interests
Lagace’s primary research interests are the cellular and molecular mechanisms that control cholesterol homeostasis and plasma lipoprotein levels, with a focus on interactions between cell surface lipoprotein receptors and their ligands.
Publications
See current publications list on PubMed.
Selected publications:
- 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.