Why Hypertension Research?
Almost half of the U.S. population has hypertension or salt sensitivity, or both. Salt sensitivity, independent of the presence of hypertension, is a risk factor not only for cardiovascular morbidity and mortality but also for other diseases, e.g., asthma, gastric carcinoma, osteoporosis, renal dysfunction, and metabolic syndrome. Although it is recognized that high sodium diet is deleterious, a low sodium diet can actually increase blood pressure in about 15-20 percent of the population and cause other adverse effects. However, the mechanisms leading to such adverse effects and whether or not they are related to interactions of “salt-resistant” and “salt-sensitive” genes are not known.
The treatment of hypertension has improved, but is successful in only about 50 percent of patients and more than one drug is usually required. The suboptimal control of essential hypertension may be related to the fact that the current treatment is empirical and not based on a priori knowledge of genetic and molecular mechanisms. A pharmacogenetics approach to hypertension treatment may provide more cost-effective therapy and allow patients to achieve blood pressure control more promptly and effectively with significant reduction of side effects and morbidity and mortality, a case for precision medicine.
Our Central Focus
Our research focuses on studying the pathogenesis and treatment of hypertension, including the roles of genetics and epigenetics, in humans, rats, and mice using molecular and cell biological methods, such as gene silencing, gene rescue, biophysical imaging, and integrated physiology. We have reported that the response to antihypertensive treatment varies according to the presence or absence of variants of a gene called G protein-coupled receptor kinase type 4 (GRK4).
• Genetics, including epistasis, and epigenetics of hypertension, especially the role of dopamine, renin-angiotensin system, and G protein-coupled receptor kinases.
• Pharmacogenetics of hypertension as a crucial tool for “precision medicine.”
• Organ-to-organ (aka "inter-organ") communication in hypertension; how the gastrointestinal tract, heart, brain, and kidney communicate in the regulation of blood pressure.
• Role of inflammation and oxidative stress in the regulation of fluid and electrolyte balance and blood pressure.
• Identifying and validating novel proteins and signaling molecules that interact with the dopaminergic system in the regulation of sodium transport and blood pressure.
How We Do It
We collaborate with basic science and translational researchers in the United States and across the world. Our research is funded by the National Institutes of Health and pharmaceutical industry.