Inflammation & Autoimmunity
Institut Pasteur de Bangui
Stavros Garantziotis, M.D., is Medical Director of the NIEHS Clinical Research Unit (CRU), head of the Matrix Biology Group, and holds a secondary appointment in the Clinical Research Branch. The group studies cell-matrix interactions in the response to environmental lung injury. Extracellular matrix (ECM) and cells are in a constant feedback relationship during development and in the tissue response to injury. Cells actively modify their ECM in the course of development, differentiation and inflammation. On the other hand, ECM can be directly altered through environmental stimuli, and the ECM milieu affects cell behavior, function and survival. Our group investigates this relationship—particularly the role of the ECM component hyaluronan—in relation to the lung response to environmental injury. Hyaluronan is an abundant ECM component, and can affect cell development, scar formation, angiogenesis and inflammation. Hyaluronan is released during environmental lung injury and sets in motion signaling responses which lead to airway inflammation, hyperresponsiveness, scarring and ultimately clinical symptoms like wheezing, cough and shortness of breath (Figure 1). The Matrix Biology Group has studies and identified signaling pathways of hyaluronan after injury (Figure 2). The group utilizes mouse models of disease, and clinical research in a “bench-to bedside-to bench” approach for high impact results. Importantly, we have identified several agents that can modify hyaluronan signaling and have potential as treatment for airway disease, and are in the process of testing their efficacy in pilot clinical studies.
The role of hyaluronan in the pulmonary response to environmental injury Mechanisms, through which cells sense their ECM during injury Clinical translation of our results into novel treatment options
Feeley, EM, Pilla-Moffett DM, Zwack EE, Piro AS, Finethy R, Kolb JP, Martinez J, Brodsky IE, and Coers J. Galectin-3 directs antimicrobial guanylate binding proteins to vacuoles furnished with bacterial secretion systems. PNAS 2017 doi: 10.1073/pnas.1615771114.
Daniels BP, Snyder AG, Olsen TM, Orozco S, Oguin TH, 3rd, Tait SW, Martinez J, Gale, M, Jr, Loo, YM, and Oberst A. RIPK3 Restricts Viral Pathogenesis via Cell Death-Independent Neuroinflammation. Cell. 2017;169(2):301-13 e11