The Newton-Cheh laboratory seeks to understand the fundamental determinants of congestive heart failure, hypertension, and life-threatening arrhythmias. We are leveraging the rapid growth of human genetics to identify novel genes and variants that underlie these diseases, to translate these genetic discoveries into an improved understanding of human pathophysiology through clinically-focused research as well as animal and cellular models, and to define the role of genetics and other factors in predicting patients’ individualized risk of disease and adverse response to therapies.
Dilated cardiomyopathy and left ventricular hypertrophy
Dilated cardiomyopathy is a major cause of congestive heart failure, causing major restrictions on activity and potentially fatal arrhythmias or progressive heart dysfunction. Left ventricular hypertrophy (LVH) is a strong risk factor for congestive heart failure, a major cause of morbidity and mortality world-wide. We are leading several large population-based studies to identify novel genetic factors that underlie dilated cardiomyopathy and LVH. Heart failure has been growing in prevalence, but our therapies have not been keeping pace. Genetics holds great promise to highlight previously unrecognized therapeutic opportunities.
Sudden cardiac death / QT interval variation / Drug-induced arrhythmias
Sudden cardiac death (SCD) is a common cardiovascular disease that claims 300,000 lives annually in the US and is influenced by genetic factors. Prolongation of the electrocardiographic QT interval is a potent risk factor for SCD and can occur as a potentially life-threatening complication of 80+ medications. We and our colleagues have identified scores of novel genes and DNA sequence variants that contribute to variability of the QT interval through the QTGEN and QT-IGC international consortia, which we have led.
Hypertension / Blood pressure regulation / Natriuretic peptides / Soluble guanylate cyclase
Elevated blood pressure (BP), or hypertension, affects an estimated 1 billion people worldwide and is a dominant factor leading to stroke, heart failure and myocardial infarction. Blood pressure is a complex trait with multiple environmental and genetic influences. It is highly heritable, but until recently the genetic causes of variation in blood pressure in the general population have been poorly defined. We and our colleagues have identified blood biomarkers and over 100 common genetic variants that contribute to blood pressure and hypertension through the Global BPgen and ICBP international consortia, which we have co-led. Our laboratory has identified the central role in BP regulation played by the natriuretic peptide and nitric oxide/soluble guanylate cyclase systems that converge on production of cyclic GMP. Our laboratory’s study of humans (at both the population and individual level) and of cellular and mouse models have pointed the way to novel therapeutic approaches to reduce blood pressure and its adverse cardiovascular consequences.