Focus on EAS Innsbruck 2016: Introducing the faculty - Plenary speaker Helen Hobbs
26 October 2015
A forward-looking scientific Programme to excite, inspire and inform!
The EAS 2016 Scientific Committee has created a programme featuring ground-breaking speakers in their respective fields. EAS 2016 Innsbruck welcomes a distinguished international faculty to share their forward-looking perspectives on the latest developments in basic research and clinical practice in atherosclerosis and cardiovascular disease. You can find details of the Plenary and Workshop sessions now on the Congress website, www.eas2016.kenes.com.
Abstract submission is now open. Submit your abstract by January 11, 2016 for the opportunity to present your findings at this prestigious international Congress.
Here, in a series of newsletters, we introduce members of the EAS 2016 Innsbruck faculty.
Plenary session 1, Monday, May 30, 2016: Integrative approach in atherosclerosis
Helen Hobbs, USA: Fatty liver disease: ancient mutations for a common disease
Helen H. Hobbs is Professor of Internal Medicine and Molecular Genetics, Director of the McDermott Center for Human Growth and Development, University of Texas (UT) Southwestern Medical Center, Dallas Texas, and an Investigator of the Howard Hughes Medical Institute. She is also Director of the Dallas Heart Study, a longitudinal, multi-ethnic, population-based study of Dallas County. After obtaining her clinical and post-doctoral training at Columbia-Presbyterian Hospital and UT Southwestern Medical Center Dallas, she joined the faculty of UT Southwestern. Her research interests focus on defining the genetic determinants of plasma lipoprotein levels and cardiovascular risk, most recently genetic variations that counter susceptibility to fatty liver disease. She is a member of the American Society for Clinical Investigation, the Association of American Physicians, the Institute of Medicine, the American Academy of Arts and Sciences and the National Academy of Sciences. She is the recipient of numerous awards including the American Heart Association Clinical Research Prize, the Heinrich Wieland Prize, the 2007 American Heart Association Distinguished Scientist Award, and the 2013 Pasarow Foundation Award in Cardiovascular Research.
Non-alcoholic fatty liver disease encompasses a spectrum of related disorders characterised by accumulation of triglycerides in hepatocytes. While usually benign, in some individuals it can progress to non-alcoholic steatohepatitis and ultimately to cirrhosis. Genome-wide association studies have provided novel insights into the genetic determinants of hepatic steatosis. Sequence variations in two genes were shown to confer susceptibility to fatty liver disease. The patatin-like phospholipase domain-containing 3 (PNPLA3) is involved in hepatocellular lipid droplet remodelling and very low-density lipoprotein (VLDL) secretion; the I148M variant is a determinant of hepatic steatosis triggered by a number of environmental factors. Additionally, the transmembrane 6 superfamily member 2 (TM6SF2) E167K gene variant, which interferes with VLDL secretion, was shown to increase susceptibility to progressive non-alcoholic steatosis by compartmentalisation of lipids within hepatocytes. This association thus refutes the idea that long-term storage of fatty acids in hepatocytes as triglycerides is benign. Other variants, including rare mutations, involved in the regulation of hepatocellular lipid metabolism, are also being investigated.
Future challenges include elucidating the molecular mechanisms underlying the association between gene variants and progressive liver disease, as well as the impact of gene variants in risk stratification, which will hopefully offer potential novel therapeutic targets.
Kozlitina J, Smagris E, Stender S, Nordestgaard BG, Zhou HH, Tybjærg-Hansen A, Vogt TF, Hobbs HH, Cohen JC. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet 2014; 46:352-6.
Wang Y, Gusarova V, Banfi S, Gromada J, Cohen JC, Hobbs HH. Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion. J Lipid Res 2015;56:1296-307.
Li JZ, Huang Y, Karaman R, Ivanova PT, Brown HA, Roddy T, Castro-Perez J, Cohen JC, Hobbs HH. Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis. J Clin Invest 2012;122:4130-44.
Hobbs and her team are one of seven main winners of the 2016 Breakthrough Prize.
Read more about the prize and the award cermony at the National Geographic news site.