Major Research Interests: Molecular Basis of Organ Fibrosis: Development of Epigenetic Fibrosis Therapy. Hyperactivity of differentiated fibroblasts causes an excessive synthesis and deposition of extracellular matrix proteins in the tissues that leads to organ fibrosis, a major cause of disease-related morbidity and mortality worldwide. Fibrosis is a common end-stage pathological symptom of a wide spectrum of injury or stress related multi-organ diseases such as hypertension-induced accelerated cardiac and renal aging, myocardial infarction, liver cirrhosis, systemic sclerosis and idiopathic pulmonary fibrosis. Epigenetics plays a key role in the development of organ fibrosis. Our research interest focuses on the role of acetyltransferase p300, a major epigenetic regulator, in TGF-beta-induced profibrogenic signal transduction and organ fibrosis. We have previously demonstrated that acetyltransferase p300 is essential for profibrogenic signal-induced matrix protein collagen synthesis. Most importantly, the levels of p300 are significantly elevated in myofibroblasts derived from resident fibroblasts or vascular endothelial cells in response to TGF-beta and different fibrotic tissues. We are interested to determine i) the molecular basis of p300 elevation in fibrotic tissues; ii) the contribution of elevated level of p300 in cardiac and renal fibrogenesis; iii) epigenetics in cardiac and renal endothelial-to-mesenchymal transition (EndMT), cellular proliferation, migration and senescence; and iv) to develop novel epigenetic therapeutic approaches targeting acetyltransferase activity of p300 to control cardiac and renal fibrosis. We are testing the therapeutic efficacies of novel small molecule inhibitors of epigenetic regulator acetyltransferase p300 for prevention and reversal of cardiac and renal fibrosis using murine models. We are also investigating the role of plasminogen activator system in air pollutants-induced cardiovascular diseases.