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This presentation was given as the Anitschkow Lecture entitled “A Journey from Plaque to Paté” at the 87th EAS Congress in Maastricht 2019, by Professor Helen Hobbs.
Helen Hobbs is professor of Internal Medicine and Molecular Genetics at the University of Texas Southwestern Medical Center. After her residency she worked as a postdoctoral fellow in the laboratory of Drs. Michael Brown and Joseph Goldstein before joining the faculty of UT Southwestern in 1987. Professor Hobbs is a pioneer in genetics, is directing the Dallas Heart Study, and uses the genetic discoveries from this study to expedite the translation of a genetic association into a therapeutic product. Her research has led to novel therapeutic approaches in the field of cardiovascular disease, most recently in the development of agents targeting. Novel strategies are targeted towards the combat of fatty liver disease. She started her Anitschkow Lecture with explaining her profound interest in cholesterol and triglycerides and gave the reason for why it is important to study these two key molecules – accumulation in the wrong tissues causes atherosclerosis and fatty liver disease. In family-studies she identified ABCG5/G8 as the genes responsible for sitosterolemia, a recessive disease characterized by plant sterol accumulation and moderate hypercholesterolemia. She moved to population studies and hypothesized that sequencing of the extremes of an intermediate trait – e.g. LDL cholesterol levels – would detect genetic variants only appearing in one extreme, and thus very likely to be functional. This approach led to the identification of protective PCSK9 variants and subsequent development of PCSK9-targeted therapeutics towards LDL cholesterol lowering and atherosclerotic cardiovascular disease. The most recent drug targets with special impact for LDL cholesterol are the ANGPLT proteins, where several therapeutical approaches targeting this family of molecules currently are being tested in clinical trials. The next wave in her scientific carrier was directed towards fatty liver disease and the interaction with genetics/ethnicity, and overweight. She and her group identified several important molecules for liver fat accumulation, and for progression from benign non-alcoholic liver fatty disease to the more severe non-alcoholic steatohepatitis. These molecules are currently being investigated for their therapeutic potential. Helen Hobbs concluded her Anitschkow Lecture by stating that the interest in two key molecules – cholesterol and triglycerides – has carried her through an exciting journey from plaque to paté.