Lars Holmgren
Studying how mechanical force controls the development of vascular diseases and cancer
The innermost layer of our blood vessels is made up of endothelial cells. These cells are affected by the continuous flow of blood in our arteries and veins. Our research group studies how the endothelium is able to resist the influence of blood circulation and how these signaling pathways affect functionality. We have identified one of many processes that are activated by the pressure of blood vessels and that cause cells to orient themselves to the flow of blood. Interestingly, this protects blood vessels from inflammatory processes and vascular diseases. One example is the formation of hernias on the body's arteries that form when the endothelium is unable to resist arterial blood flow. We have also identified a possible drug that could prevent these disease processes.
The junctional mechanosensor AmotL2 regulates YAP promoter accessibility
Aarren J Mannion, Honglei Zhao, Yuanyuan Zhang, Ylva von Wright, Otto Bergman, Pipsa Saharinen, Lars Holmgren. bioRxiv
Yuanyuan Zhang, Evelyn Hutterer, Sara Hultin, Otto Bergman, Maria J Forteza, Zorana Andonovic, Daniel FJ Ketelhuth, Joy Roy, Per Eriksson, Lars Holmgren. bioRxiv
The Amot/integrin protein complex transmits mechanical forces required for vascular expansion.
Zhang Y, Zhang Y, Kameishi S, Barutello G, Zheng Y, Tobin NP, Nicosia J, Hennig K, Chiu DK, Balland M, Barker TH, Cavallo F, Holmgren L.Cell Rep. 2021 Aug 24;36(8):109616. doi: 10.1016/j.celrep.2021.109616.PMID: 34433061
Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice.
Rojek KO, Krzemień J, Doleżyczek H, Boguszewski PM, Kaczmarek L, Konopka W, Rylski M, Jaworski J, Holmgren L, Prószyński TJ.PLoS Biol. 2019 May 1;17(5):e3000253. doi: 10.1371/journal.pbio.3000253. eCollection 2019 May.PMID: 31042703
AmotL2 links VE-cadherin to contractile actin fibers necessary for aortic lumen expansion.
Hultin S, Zheng Y, Mojallal M, Vertuani S, Gentili C, Balland M, Milloud R, Belting HG, Affolter M, Helker CS, Adams RH, Herzog W, Uhlen P, Majumdar A, Holmgren L.Nat Commun. 2014 May 7;5:3743. doi: 10.1038/ncomms4743.PMID: 24806444