Our research group includes two teams: One team studies the role of phospholipase A2 (PLA2) in inflammtory/allergic processes, and their control by PLA2 inhibition. The other team, headed by Dr. Gregory Barshtein, studies the role of red blood cell (RBC) flow properties in cardiovascular and inflammatory conditions.
Role of phospholipase A2 in inflammatory/allergic processes: Phospholipase A2 (PLA2), which hydrolyzes cell membrane phospholipids (PL), is a super family of enzymes that consists of two main kinds: the secreted (sPLA2) and the intracellular (cPLA2and iPLA2) enzymes. By hydrolyzing cell membrane PL, PLA2 initiates the production of numerous metabolites that mediate diverse pathological states, particularly those related to inflammatory processes. These includes mainly lyso-phospholipids (LysoPL and PAF), as well as arachidonic acid, which is metabolized by the cyclooxygenase (COX) pathways into prostaglandins or by the lipoxygenase (LOX) pathways into leukotrienes - many of them involved in the development of numerous pathological conditions, especially in inflammation-related processes. PLA2 enzymes, sPLA2 in particular, are also linked to cell signaling and production of inflammatory cytokines, apart from their lipolytic activity. In inducing inflammatory processes, the PLA2 enzymes may act independently, in synergism, or in antagonism. To differentiate between the contributions of the PLA2 iso-enzymes, we have designed and synthesized a prototype of cell-impermeable extracellular sPLA2 inhibitors (ExPLIs), which control PL hydrolysis at the cell membrane without directly affecting intracellular activities. Using the ExPLIs, we have studied the involvement of PLA2s in diverse inflammatory/allergic conditions, in cell cultures and animal models (see Publications). The interrelationship and cross-talk between the PLA2 iso-enzymes is the focus of our current research.
Role of red blood cell (RBC) flow properties in cardiovascular and inflammatory conditions: Red blood cells (RBC) have special properties that are key determinants in blood flow and hemodynamics: These are their aggregability (tendency to form multi-cellular self aggregates), deformability, flexibility (ability to change their shape in order to pass through blood capillaries), and potential adherence to blood vessel wall endothelium. Normally, RBC are singly dispersed, sufficiently deformable, and their adherence to vessel wall is negligible. However, under pathological conditions, mainly cardiovascular, inflammatory and oxidative stress states, RBC aggregability, rigidity and adherence are enhanced, resulting in flow hindrance and irregular flow patterns, leading to reduced tissue perfusion and infarct. To comprehensively investigate the role of RBC hemodynamics in the pathophysiology of circulatory disorders, we have designed and constructed a unique computerized cell flow properties analyzer (CFA), which enables the direct visualization and monitoring of the dynamic organization of RBC in a narrow-gap flow chamber, under controllable flow conditions resembling those in a microvessel. The CFA, which is a most advanced and sophisticated imaging system for in-vitro monitoring of RBC hemodynamics, provides an array of parameters, some newly defined, for comprehensive characterization on RBC flow properties and their alteration in pathological conditions. The CFA has been employed in a number of laboratories for studying the involvement of RBC flow properties in the pathophysiology of cardio-vascular and inflammatory conditions, as well as for studying effects of blood banking procedures on the hemodynamic behavior of blood for transfusion therapy. Our current research focuses on elucidating biochemical and physical factors in RBC that are responsible for the alteration of their flow properties in pathological conditions and during blood banking procedures [For details click here].
1977: The Hebrew University-Hadassah Medical School Prize for Ph. D. Thesis.
1988: The Cystic Fibrosis Foundation award for novel ideas, NIH, Bethesda, MD.
1999: The Henri de Rothchild Award, Institute Curie, Orsay, France.