The diabetes mellitus is growing rapidly, about 90% of them are type 2 diabetes (T2D), which increases the risk for cardiovascular diseases. The heart is not the organ playing a central role in the pathophysiology of T2D, however, cardiovascular diseases are the leading cause of diabetes related mortality. Although the causes of T2D associated heart diseases are multifactorial, extensive epidemiological studies suggest that diabetes mellitus can affect cardiac structure and function independent of vascular diseases or hypertension, termed diabetic cardiomyopathy (DCM) demonstrating significant impairment in cardiac metabolic flexibility. Abnormal usage of cardiac metabolic substrate (glucose and fatty acid) in diabetes leads to severe cardiac lipotoxicity, insulin resistance, ROS accumulation, and mitochondrial dysfunction, which contributes to cardiac dysfunction eventurally. However, the molecular mechanisms of metabolic responses and energy adaption are largely unknown.
The main research interest in my group is to elucidate the novel understandings of molecular mechanisms underlying adaption of cardiac energy to the changing metabolic environment (including cell signalling pathways, endoplasmic reticulum stress involvement, pro-inflammatory cytokines stress, and epigenetic regulation, etc.). Additionally, we aim to explore the novel gene or pharmacological therapies and alternative remedies in disease conditions such as diabetes, hypertension, ischemic heart disease and heart failure. For achieving this, I would like to create gene modified animal models using Flox/Cre system, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system, or adeno-associated virus (AAV) delivery. In addition, induced human pluripotent stem (iPS)-cardiomyocytes will be used for prospective drug screening and development for treatment of cardiovascular disease caused by metobolic disorders.
gene function, molecular mechanism, and treatment development of cardiovascular diseases.