Stavros Garantziotis, M.D.
Immunity, Inflammation, and Disease Laboratory/Matrix Biology Group
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 agents that can modify hyaluronan signaling and have potential as treatment for airway disease and testing their efficacy in clinical studies.
More recently, we discovered a role in environmental lung injury for certain cell surface receptors which recognize not only hyaluronan but also bacterial wall proteins. Through this insight we were able to uncover an important role for the microbiome in lung injury. Our research suggests that a healthy microbiome promotes lung health as well and protects against the development of diseases such as emphysema and idiopathic pulmonary fibrosis. Excitingly, we may be able to distill the microbiome effect down to single proteins, that can be then given to patients as treatment. We have partnered with a company to pursue this goal and are looking forward to translating our basic insights into the clinic.
Garantziotis obtained his medical degree at the Albert-Ludwigs-University in Freiburg, Germany. After an internship in Internal Medicine at the University Hospital in Munich, Germany, he completed his residency in Internal Medicine at the Albert Einstein College of Medicine of Yeshiva University in New York, New York, and received his Board Certification in Internal Medicine. He then completed a fellowship in the Division of Pulmonary, Allergy and Critical Care Medicine at Duke University Medical Center, and received Board Certification in Pulmonary Medicine and Critical Care Medicine. Garantziotis remained a faculty member in the Division until he joined the NIEHS to set up and supervise the new CRU. In addition to his role as Principal Investigator and Medical Director of the CRU, he was Acting Clinical Director from 2013-2015.
- Galdi F, Pedone C, McGee CA, George M, Rice AB, Hussain SS, Vijaykumar K, Boitet ER, Tearney GJ, McGrath JA, Brown AR, Rowe SM, Incalzi RA, Garantziotis S. Inhaled high molecular weight hyaluronan ameliorates respiratory failure in acute COPD exacerbation: a pilot study. Respir Res. 2021;22(1):30.
- Hussain S, Johnson CG, Sciurba J, Meng X, Stober VP, Liu C, Cyphert-Daly JM, Bulek K, Qian W, Solis A, Sakamachi Y, Trempus CS, Aloor JJ, Gowdy KM, Foster WM, Hollingsworth JW, Tighe RM, Li X, Fessler MB, Garantziotis S. TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injury. Elife. 2020;9.
- Wilson RH, Maruoka S, Whitehead GS, Foley JF, Flake GP, Sever ML, Zeldin DC, Kraft M, Garantziotis S, Nakano H, Cook DN. The Toll-like receptor 5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens. Nat Med. 2012;18(11):1705-10.
- Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, Fingerlin TE, Zhang W, Gudmundsson G, Groshong SD, Evans CM, Garantziotis S, Adler KB, Dickey BF, du Bois RM, Yang IV, Herron A, Kervitsky D, Talbert JL, Markin C, Park J, Crews AL, Slifer SH, Auerbach S, Roy MG, Lin J, Hennessy CE, Schwarz MI, Schwartz DA. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;364(16):1503-12.
- Schurman SH, Bravo MA, Innes CL, Jackson WB 2nd, McGrath JA, Miranda ML, Garantziotis S. Toll-like Receptor 4 Pathway Polymorphisms Interact with Pollution to Influence Asthma Diagnosis and Severity. Sci Rep. 2018;8(1):12713.
Related Scientific Focus Areas
This page was last updated on Friday, August 18, 2023