Chemical Physics Seminar: Extracellular matrix remodeling: from biophysical principles to drug design
Prof. Irit Sagi, Weizmann Institute of Science
Remodeling of collagenous matrix is a hallmark of various pathological conditions including tissue injury, fibrosis, malignancy and infection. To date, sporadic reports suggested a link between pathological extracellular matrix (ECM) remodeling and immune cells, with little to no mechanistic information. While most biological research centers on what goes on inside the cell, we look at what goes on outside the cell. Utilizing integrated biophysical-biochemical experimental scheme our lab focuses on the cell microenvironment which includes the extracellular matrix; a collection of extracellular molecules secreted by cells that provides structural and biochemical support to the surrounding cells and multifunctional neighboring cells. We have found that ECM enzymes, which can induce morphological changes in the matrix, affect cellular programming. This provides us with significant opportunities to influence cellular programming and interfere in disease as well as with developmental processes that affect intimate cellular communications at the very near microenvironment of cancer and inflammatory cells and reproduction. By implementing our discoveries into the design of novel molecular agents targeting physiological as well as pathological ECM proteolysis we can impact invasive diseases by protecting ECM molecular integrity and morphology. In my talk I will cover aspects of implementing biophysical principles of tissue remodeling into the rationalization of novel drugs for invasive diseases.
Solomonov I, et al (2016). Combinatorial Programming of ECM by Homologous Collagenases Generates Differential Cell Behavior and Transcription. PNAS USA, 113, 10884-10889.
Mohan, V., et al (2016) Matrix Metalloproteinase Protein Inhibitors: Highlighting a New Beginning for Metalloproteinases in Medicine. Metalloproteases in Medicine, 3, 31-47.
Talmi-Frank D., et al (2016). Dysregulated Proteolysis of Extracellular Matrix Proteins Regulates Influenza and Pneumonia Co-infection Associated Mortality. Cell Host & Microbes, 20, 458-470.
Elad Bassat et al (2017). The extracellular matrix protein agrin promotes heart regeneration in mice. Nature. 2017 Jul , 547 (7662):179-181.
Seminar Organizers: Dr. Sharly Fleischer and Dr. Tal Schwartz