Molecular and Cellular Basis of Cardiovascular and Renal Diseases
Our long-term goal is to identify and characterize genes that may be involved in cardiovascular and renal diseases for the purpose to develop preventive strategies and therapeutic approaches. Currently, we are assessing the role of a recently-discovered anti-aging gene klotho in the pathogenesis of hypertension, kidney injury, and artery stiffening. The cellular and molecular mechanisms that mediate the role of klotho in cardiovascular and renal diseases are being investigated.
Cold Temperatures and Cardiovascular Disease
It is well established that people who live and work in (north) cold regions have a high incidence of hypertension and related cardiovascular diseases. Cold temperatures (weather) make hypertension severer and induce myocardial infarction and stroke in hypertensive patients. Of the four seasons that occur in the US, the cold winter has the highest mortality and morbidity from cardiovascular diseases. Studies from our lab have shown that chronic or intermittent exposure of rats and mice to moderate cold (5°C; 41°F) induces hypertension and cardiac/renal hypertrophy within 3 weeks. The roles of the renin-angiotensin-aldosterone system (RAAS), the endothelin system, nitric oxide, and oxidative stress and their relationship in cold-induced hypertension and cardiac hypertrophy have been determined. Our lab is currently evaluating the cellular and molecular mechanisms contributing to cold-induced hypertension and cardiac/renal injuries.
Molecular Therapy for Cardiovascular and Renal Diseases
The current antihypertensive drugs are short-lasting, lack of specificity, and thus have side effects and poor tolerance. Therefore, our laboratory is aiming for the development of a long-term and effective therapy for hypertension with minimum side effects. Molecular therapy offers a possibility of producing longer-lasting effects with precise specificity based on the genetic design. Our lab is currently using viral and non-viral approaches to down-regulate vasoconstrictor genes and/or to up-regulate vasodilator genes for the optimal treatment of hypertension and related cardiovascular/renal disease. The genes targeted include endothelin, endothelial NO synthase (eNOS), NADPH oxidases, c-myc, and klotho. The cardiac myocyte-specific gene delivery is used for the study of molecular mechanisms of cardiac hypertrophy. The AAV vectors and nanoparticles are employed for delivering therapeutic genes to cardiac myocytes, renal tubule epithelial cells, vascular smooth muscles, and endothelial cells.
Molecular and Biochemical Basis of Autism and Schizophrenia
A strong link between autism, schizophrenia and diet has been reported by our group. Casein- and/or gluten-free diet significantly improved the symptoms associated with autism and schizophrenia. The overall hypothesis is that autism and schizophrenia are caused by an excessive accumulation of exogenous and/or endogenous bioactive peptides. An abnormal accumulation of bioactive peptides may be due to genetically-determined deficiency in enzyme or peptidase. Our current goal is to identify and characterize the candidate genes of the deficient peptidases and to develop therapeutic approaches for these mental disorders.