Ploug Group

Our research focus on structural and functional aspects of proteins involved in disease relevant pathways. The ultimate goal of these studies is to elucidate the function of these proteins in vitro and in vivo and to facilitate the translation of these findings into a clinical setting, particularly within the field of oncology and lipid metabolism.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

These discoveries were made by harvesting the full synergy from interactive collaborations.

1: Revised the paradigm for intravascular lipid metabolism—intrinsic protein disorder in GPIHBP1 secures proper compartmentalization of lipoprotein lipase (LPL) and stabilizes the enzyme against spontaneous inactivation.

  • Mysling S, et al. (2016) The acidic domain of the endothelial membrane protein GPIHBP1 stabilizes lipoprotein lipase activity by preventing unfolding of its catalytic domain. Elife 5:e12095
  • Kristensen KK, et al. (2018) A disordered acidic domain in GPIHBP1 harboring a sulfated tyrosine regulates lipoprotein lipase. Proceedings of the National Academy of Sciences of the United States of America 115(26):E6020
  • Song, W, et al. (2022) Electrostatic sheating of lipoprotein lipase is essential for its movement across capillary endothelial cells. J Clin Invest 132 (5):e157500

2: Discovered a new mechanism for LPL regulation—the inhibitor ANGPTL4 catalyzes a cooperative allosteric unfolding leading to the irreversible collapse of LPL’s catalytic triad while the activator APOC2 stabilizes these regions.

  • Mysling S, et al. (2016) The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 counteracts this unfolding. Elife 5:20958
  • Kristensen KK, et al. (2020) Unfolding of monomeric lipoprotein lipase by ANGPTL4: Insight into the regulation of plasma triglyceride metabolism. Proceedings of the National Academy of Sciences of the United States of America 117(8):4337
  • Leth-Espensen KZ, et al. (2021) The instrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding Proceedings of the National Academy of Sciences of the United States of America 118(12): e2026650118

Kumari A, et al. (2023) Inverse effects of APOC2 and ANGPTL4 on the conformational dynamics of lid-anchoring structures in lipoprotein lipase Proceedings of the National Academy of Sciences of the United States of America 120(18): e2221888120 3: Solved the first crystal structure of LPL.

  • Birrane G, et al. (2019) Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis. Proceedings of the National Academy of Sciences of the United States of America 116(5):1723–1732

 4: Discovered a new etiology for acquired chylomicronemia

  • Beigneux AP, et al. (2017) Autoantibodies against GPIHBP1 as a Cause of Hypertriglyceridemia. N Engl J Med 376(17):1647–1658
  • Lutz J, et al. (2020) Chylomicronemia from GPIHBP1 autoantibodies successfully treated with rituxumab: A case report. Ann Intern Med. doi:7326/L20-0327

 5: Developed a peptide probe for non-invasive imaging of solid cancers lesions.

  • Persson M, et al. (2015) First-in-human uPAR PET: Imaging of cancer aggressiveness. Theranostics 5(12):1303–1316
  • Leth JM & Ploug M (2021) Targeting the urokinase-type plasminogen activator (uPAR) in human diseases with a view to non-invasive imaging and therapeutic intervention. Front Cell Dev Biol 9: PMID: 34490277

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Selected publications

Kumari A, Grønnemose AL, Kristensen KK, Winther AL, Young SG, Jørgensen TJD, and Ploug M. “Inverse effects of APOC2 and ANGPTL4 on the conformational dynamics of lid-anchoring structures in lipoprotein lipase”
Proc. Natl. Acad. Sci. 120 (2023) PMID: 37094117

Leth-Espensen KZ, Kristensen KK, Kumari A, Winther AL, Young SG, Jørgensen TJD, Ploug M. The instrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding”
Proc. Natl. Acad. Sci. 118 (2021) e2026650118

Kristensen, K.K., Leth-Espensen, K.Z., Mertens, H.D.T., Birrane, G., Meiyappan, M., Olivecrona, G., Jørgensen, T.J.D., Young, S.G., and Ploug, M. Unfolding of monomeric lipoprotein lipase by ANGPTL4: Insight into the regulation of plasma triglyceride metabolism
Proc. Natl. Acad. Sci. 117 (2020) 4337−4346

Young, S.G., Fong, L.G., Beigneux, A., Allan, C.M., He, C., Nakajima, K., Meiyappan, M., Birrane, G., and Ploug, M. GPIHBP1 and lipoprotein lipase, partners in plasma triglyceride metabolism”
Cell Metabolism 30 (2019) 51−65

Kristensen, K.K., Midtgaard, S.R., Mysling, S., Korov, O., Hansen, L.B., Skar-Gislinge, N., Kragelund, B.K., Olivecrona, G., Young, S.G., Jørgensen, T.J.D., Fong, L.G., and Ploug, M. A Disordered Acidic Domain in GPIHBP1 haboring a Sulfated Tyrosine regulates Lipoprotein Lipase
Proc. Natl. Acad. Sci. 115 (2018) E6020-E6029

Mysling, S., Kristensen, K.K., Larsson, M., Beigneux, A.P., Gårdsvoll, H., Fong, L.G., Bensadoun, A., Jørgensen, T.D., Young, S.G., and Ploug, M. The acidic domain of the endothelial membrane protein GPIHBP1 stabilizes lipoprotein lipase activity by preventing unfolding of its catalytic domain
eLife (2016) doi: 10.7554/eLife.12095

Mysling, S., Kristensen, K.K., Larsson, M., Korov, O., Bensadoun, A., Jørgensen, T.J.D., Olivecrona, G., Young, S.,  and Ploug, M. The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 counteracts this unfolding 
eLife (2016) doi: 10.77554/eLife.20958

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