Biology

Prof. Irit Sagi
Weizmann Institute of Science, Israel

The extracellular matrix (ECM) is an essential mediator of tissue function that provides both chemical and mechanical stimuli to influence cellular behavior in both health and disease. Remodeling of cellular microenvironments, including its biomineralization, and ECM by enzymes such as matrix metalloproteases (MMPs/ADAMs) and lysyl oxidases (LOX/LOXL) is a fundamental process, which is why its importance is becoming increasingly acknowledged. However, formidable challenges remain towards identifying the diverse and novel roles of such enzymatic ECM reactions, especially with regard to their distinct biophysical, biochemical, and cellular impact. Considering the heterogeneous, dynamic and hierarchical nature of both the ECM and cellular microenvironments, we set to decipher remodeling molecular mechanisms dictating cell behavior in various physiological and pathological scenarios. Accordingly, we utilize a multidisciplinary integrated research scheme which provides a three-dimensional functional molecular view of ECM remodeling, driven by proteolysis and covalent collagen cross linking. Subsequently, we employ systems biology tools to reveal changes in ECM molecular compositions, focusing on native and reconstituted ECM environments. By implementing our discoveries of these highly selective functions, into the design of novel molecular agents targeting pathological ECM remodeling.