Kavdia Research Lab’s interests are in the area of the computational biology and medicine and integrative vascular physiology. The integrative term has two meaning: (1) integrate at multi-scale from molecular, cellular, tissue and organ level and (2) integrate computational and experimental approaches to understand a particular biological or physiological system.

Specifically, the Kavdia Lab’s goal is to provide quantitative analyses of oxidative and nitrosative stress in vascular tissue and understand the endothelial dysfunction. A quantitative understanding of endothelial dysfunction would lead to our understanding of mechanisms responsible for cardiovascular diseases, pulmonary hypertension, atherosclerosis, and ischemic-reperfusion injuries, diabetes, and aging and can provide guidelines for therapeutics for these conditions.

We use the techniques of computational modeling, mammalian cell culture, hematology, cell signaling pathways, biochemical kinetics and biotransport, fluorescence microscopy, absorption and fluorescence spectroscopy in order to accomplish these goals.

Nitric Oxide (NO) Biotransport: NO plays key role in numerous physiological functions including endothelium-derived relaxation, platelet inhibition, smooth muscle proliferation, neurotransmission and host defense. Its role as a vasodilator has been established over last two decades. However, the fate of NO when it enters the bloodstream is still not established. The overall objective of the proposed research is to use computational modeling and in vitro experiments to improve our understanding of the NO biotransport in the Microcirculation. For this purpose, we are designing an in vitro model systems of the microcirculation. Using chemiluminescence analyzer (Sievers Model 280i), experimental measurements of end-products concentration of NO metabolism are performed to quantify NO interactions with biomolecules including plasma constituents and red blood cell. Detailed computational models are being developed to (a) simulate NO metabolism in in vitro experimental system and (b) simulate NO transport in the microcirculation.

By designing a new experimental model for studying biochemical interactions of nitric oxide and red blood cell, we are advancing the knowledge of biomedical researchers on these molecular interactions and may provide therapeutic opportunities in areas as diverse as sickle cell anemia, pulmonary hypertension, septic shock, nitric oxide inhalation, and blood substitutes.

Endothelial Dysfunction: The primary marker generally used for endothelial dysfunction is reduced bioavailability of endothelial cell-released nitric oxide (NO). Numerous studies point to the overproduction of reactive oxygen species including superoxide resulting from oxidative stresses is the first and key event in endothelial dysfunction. The underlying mechanisms of oxidative stress induced endothelial cell dysfunction remain poorly understood. The factors that leads to endothelial cell dysfunction include enzyme systems, cofactors/ substrate availability, antioxidants, and cellular location. These reactive oxygen species can directly interact with nitric oxide or serve as signaling molecules to modulate release of nitric oxide by endothelial cells. This can be linked to the amount of peroxynitrite generation at the endothelial cell level. We are developing computational models to predict levels of NO, superoxide & peroxynitrite at the endothelial cell level.

In addition, we are using an in vitro shear stress experimental system to expose HUVECs oxidative stresses related conditions. Knowledge of underlying mechanisms of molecular interactions in oxidative stresses will be useful in developing new treatment and rationalizing the use of existing treatment in cardiovascular disorder, diabetes and age related vascular complications.