Partner 1: Karolinska Institutet (KI), Stockholm, Sweden 
KI is one of the world´s leading medical universities and its mission is to contribute to the improvement of human health through research and education. KI offers the Swedens broadest range of education in medicine and health sciences.
Partner 1c team leader:
Professor Paolo Parini
Inflammation and Infection Theme, Karolinska University Hospital
and Clinical Chemistry, Department of Laboratory Medicine,
and Metabolism Unit, Depatment of Medicine
paolo.parini@ki.se
The Lipo Group Research Constellation (LGRC) led by Paolo Parini investigates lipoprotein and lipid metabolism in human and preclinical models. A particular focus of the researches is the sex-related differences, the species differences and regulation of metabolism at molecular levels. The access to patients, to mouse-models, and in vitro systems underscore the translational nature of the research activities of the group. The research is also highly innovative by proposing new therapeutic targets for the prevention of cardiovascular and metabolic diseases.
Dr. Parini will coordinate HUMAN and also participate in the Executive Committee. Dr. Parini and his team will be involved in WP3 and will determine if the liver humanised mouse model recreates the hallmark metabolic characteristics of a human liver and will characterise changes in clinical metabolic parameters of disease and aging. A comprehensive analysis of cholesterol, bile acid, lipid, apolipoproteins and carbohydrate metabolism will be performed.
Over the last decade the LGRG investigated the lipoprotein and lipid metabolism at molecular levels in both clinical and preclinical models. The group has identified new sex-related differences in human metabolism that in part contribute to explain the sex-related difference in cardiovascular disease. The group has also identified important species related differences in liver metabolism. Finally, the LGRC has unravelled new molecular effects of cholesterol synthesis inhibition by statins in human liver. LGRC also offers a unique competence and technological platform to drive studies for: a) pharmacological target validation, b) evaluation of lipid and glucose metabolism, c) detailed characterization of lipoprotein composition, structure and functionsDr. Parini is the former chairman of the Scandinavian Society for Atherosclerosis Research (SSAR), and he has been recently elected as Treasurer of the European Atherosclerosis Society (EAS). He has founded the consulting company PPC AB and has minor propriety interest in the Swedish biotec company Triple Crown AB. Dr. Parini serves as consultant for different Big Parma, smaller biotech companies and for food companies (Sweden).
Relevant publications:
1) Pramfalk C, et al. (2011) Effects of high dose statin on the human hepatic expression of genes involved in carbohydrate and triglyceride metabolism. J Int Med. 269:333-339
2) Parini P, et al. (2009) ACAT2 and human hepatic cholesterol metabolism: identification of important gender-related differences. Atherosclerosis. 207:266-271
3) Pramfalk C, et al. (2009) Control of ACAT2 liver expression by HNF4α: relevance for low esterified cholesterol in lipoproteins from MODY1 patients. Arterioscler Thromb & Vasc Biol. 29:1235-1241.
4) Johansson L, et al. (2005) Selective thyroid receptor modulation by GC-1 reduces serum lipid levels and stimulates steps of reverse cholesterol transport in euthyroid mice. Proc Natl Acad Sci USA. 102:10297-10302.
5) Parini P, et al. (2004) ACAT2 is localized to hepatocytes and is the major cholesterol esterifying enzyme in human liver. Circulation. 110:2017-2023.