 |
|
Dr. H. Linda Cai, MD, PhD Chief Investigator Cai Laboratory Email: hcai@mednet.ucla.edu Phone: (310) 267-2303 Fax: (310) 825-0132 UCLA David Geffen School of Medicine Department of Anesthesiology Division of Molecular Medicine 10833 Le Conte Ave BOX 951778, BH - 550 CHS Los Angeles, CA 90095-1778 |
|
|
|
|
|
|
|
|
|
Welcome to the homepage of the Cai Laboratory! We belong to the Division of Molecular Medicine, Department of Anesthesiology. As the Principle Investigator of the group, I appreciate you visiting our webpage and hope that you find our research exciting.
We are interested in reactive oxygen species regulation of endothelial nitric oxide synthase (eNOS) expression and function, and its consequences regarding nitric oxide bioavailability and development of cardiovascular diseases. Nitric oxide is an important signaling molecule. It relaxes vascular smooth muscle to dilate blood vessels. It also inhibits a variety of pathological events such as activation of platelets and induction of inflammatory proteins. Loss of nitric oxide leads to high blood pressure and atherosclerotic vascular diseases. It is of great clinical significance to fully understand regulation of nitric oxide bioavailability at molecular levels.
Data accumulated in the past decade have shown that production of reactive oxygen species is increased in aging, cardiovascular and pulmonary diseases, neurodegenerative disorders and angiogenesis. An important consequence of excessive production of reactive oxygen species is oxidative inactivation of nitric oxide. For example, superoxide radicals rapidly react with nitric oxide to form peroxynitrite, resulting in immediate loss of nitric oxide. Additional recent studies suggest that reactive oxygen species can oxidize tetrahydrobiopterin, an essential cofactor for eNOS. This response leads to a condition where eNOS produces superoxide rather than nitric oxide. This "uncoupling" phenomenon of eNOS likely prolongs oxidant stress. Our goal is to characterize in-depth the molecular mechanisms whereby eNOS uncouples under disease states. This will ultimately lead to discovery of novel therapeutics restoring nitric oxide production from uncoupled eNOS, in other words, "recoupling" of eNOS.
One project in the lab is to explore molecular mechanisms of eNOS uncoupling in various forms of vascular disease like hypertension using a combination of cell biological, genetic and physiological tools. We are also interested in reactive oxygen species regulation of angiogenesis, cytoskeleton reorganization in endothelial cells and free radical regulation of endocardial function. An innovative project exploring molecular mechanisms underlying cardiovascular side effects of cancer drugs is also currently ongoing in the laboratory.
Current Research Projects:
eNOS uncoupling by Angiotensin II
Angiotensin II and Diabetic Vasculopathy
Recoupling of eNOS in Hypertension
Reactive Oxygen Species and Actin Cytoskeleton
Angiogenesis and Free Radicals
Cardiovascular Complications of Cancer Drugs
