The endothelium functions as a semi-permeable barrier between the blood plasma and interstitium thus regulating tissue fluid homeostasis. Impairment of the endothelial barrier is a key early event in the development of Adult Respiratory Distress Syndrome (ARDS). This condition is clinically manifested as a severe loss of gas exchange capacity and hypoxemia that is often fatal.
The focus of my research is on the cross-talk between microtubule cytoskeleton and VE-cadherin-mediated adhesions in lung microvascular endothelial cells. Dynamic interaction between cytoskeleton and adherens junctions is known to be important for maintenance of basal endothelial barrier permeability and underlies changes in endothelial permeability in response to different mediators. I am investigating the molecular and signaling mechanisms regulating microtubule cytoskeleton downstream of adherens junction and how changes in microtubule dynamics affect integrity of endothelial monolayer in response to extracellular stimuli. By establishing how MTs mediate increased lung vascular permeability we will be in a position to define novel therapeutic targets to treat ARDS.
Y.A. Komarova, S.M. Vogel, A.B. Malik “IP3R derivative peptide prevents inflammation-induced pulmonary vascular leakage and lethality in sepsis”. USA Provisional Patent, DD060