Group: Unit of Lipid Signaling and Homeostasis, Minerva Foundation Institute for Medical Research, Biomedicum 2U, Tukholmankatu 8, FI-00290 Helsinki, Finland
Key members: Vesa Olkkonen, Matti Jauhiainen, P.A. Nidhina Haridas, Amita Arora, Henriikka Kentala, Annika Koponen, Hanna Ruhanen, Maria Ahonen, Jari Metso, Eeva Jääskeläinen
Research activities: One of the main aims of the group aims to elucidate how cells maintain the specific lipid compositions of their organelles and sense their internal lipid status to control vital cellular processes such as signal transduction, vesicle transport, motility and proliferation. A novel concept, that of membrane contact sites (MCSs), zones of close contact between the limiting membranes of intracellular organelles, has in the recent years moved into the focus of biomedical research. A major project in the group aims to unravel the function of the oxysterol-binding protein (OSBP)-related (ORP) family and other new MCS components, as well as their roles in diseases involving aberrant lipid transport or signaling. The work involves molecular cell biology and biochemistry approaches as well as animal models. A second major activity focuses on novel molecular machineries involved in the development of obesity, insulin resistance, type 2 diabetes and atherosclerotic cardiovascular diseases (CVDs). Key focus areas here are (i) the function of angiopoietin-like proteins (ANGPTL) 3, 4, and 8 as regulators of lipid metabolism and insulin sensitivity, and (ii) analysis of HDL subspecies to explore their potential in risk assessment and monitoring of atherosclerotic coronary artery disease.
Key papers related to ENOR:
Analysis of ORP2 knock-out hepatocytes uncovers a novel function in actin cytoskeletal regulation. Kentala H, Koponen A, Kivelä A, Andrews R, Li C, You Z, Olkkonen VM. FASEB J. 2017, Nov 1. pii: fj.201700604R. doi: 10.1096/fj.201700604R. [Epub ahead of print].
A loss-of-function variant in OSBPL1A predisposes to low plasma HDL cholesterol levels and impaired cholesterol efflux capacity. Motazacker MM, Pirhonen J, van Capelleveen JC, Weber-Boyvat M, Kuivenhoven JA, Shah S, Hovingh GK, Metso J, Li S, Ikonen E, Jauhiainen M, Dallinga-Thie GM, Olkkonen VM. Atherosclerosis. 2016, 249:140-7.
MicroRNA-221-3p Regulates Angiopoietin-Like 8 (ANGPTL8) Expression in Adipocytes. Mysore R, Ortega FJ, Latorre J, Ahonen M, Savolainen-Peltonen H, Fischer-Posovszky P, Wabitsch M, Olkkonen VM, Fernández-Real JM, Haridas PAN.
J Clin Endocrinol Metab. 2017, 102:4001-12.
Effects of angiopoietin-like protein 3 deficiency on postprandial lipid and lipoprotein metabolism. Minicocci I, Tikka A, Poggiogalle E, Metso J, Montali A, Ceci F, Labbadia G, Fontana M, Di Costanzo A, Maranghi M, Rosano A, Ehnholm C, Donini LM, Jauhiainen M, Arca M. J Lipid Res. 2016, 57:1097-107.