My laboratory is studying the molecular events that dictate the foreign body response (FBR) to biomaterials. We have identified modifiers of the FBR such as MCP-1, MMP-9 and TSP2. MCP-1 and MMP-9 are required for monocyte fusion and formation of foreign body giant cells. Our biomaterial studies include skin and brain implants. Monocytes undergoing fusion display changes in cell shape and formation of lamellipodia. We have shown that these processes depend on the activation of Rac1, and we have developed strategies to block its activation. Our angiogenesis-related research is focused on TSP2, an inhibitor of angiogenesis. We are utilizing a three-dimensional assay to investigate its effects on endothelial cells. Our aim is to identify the signals propagated by TSP2. Recently, we have found that TSP2 is critical for the recovery of blood flow in ischemia and that its expression is regulated by nitric oxide. We are examining the role of nitric oxide in controlling TSP2 levels during arteriogenesis and angiogenesis.
Extensive Research Description
Our specialized research interests include cellular and molecular events; the interface between implanted biomaterials and tissues; biomaterial-induced inflammation, wound healing, tissue regeneration with a focus on angiogenesis, and extracellular matrix remodeling; in vivo work on genetically-modified mice; gene delivery from biomaterials; development of bioactive and biodegradable polymers; modification of glucose sensors; development of artificial skin.
- Malik AF, Hoque R, Ouyang X, Ghani A, Hong E, Khan K, Moore LB, Ng G, Munro F, Flavell RA, Shi Y, Kyriakides TR, Mehal WZ. Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response. Proc Natl Acad Sci U S A. 2011 108(50):20095-100.
- MacLauchlan S, Yu J, Parrish M, Asoulin TA, Schleicher M, Krady MM, Zeng J, Huang PL, Sessa WC, Kyriakides TR. Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2. Proc Natl Acad Sci U S A. 2011 108(46):E1137-45.
- Kyriakides T.R., MacLauchlan S. (2009) The role of thrombospondins in wound healing, ischemia, and the foreign body reaction. J. Cell Comm. Signal. 3: 215-25.
- Zhou J, Tang PC, Gayed PM, Li W, Skokos EA, Kyriakides TR, Pober JS, Tellides G. CXCR3-dependent accumulation and activation of perivascular macrophages is necessary for homeostatic arterial remodeling to hemodynamic stresses. J. Exp. Med. 207:1951-66, 2010.
- W. Tian, T.R. Kyriakides Matrix metalloproteinase-9 deficiency leads to prolonged foreign body response in the brain associated with increased IL1-ß levels and leakage of the blood brain barrier. Matrix Biology 28: 148-59, 2009.
- MacLauchlan S., Skokos E., Meznarich N., Zhu D., Raoof S., Shipley J.M., Senior R.M., Bornstein P., Kyriakides T.R.. Abnormal foreign body response in mice that lack matrix metalloproteinase-9 associated with disordered matrix remodeling, compromised angiogenesis, and foreign body giant cell formation. J. Leukocyte Biology 85:617-26. 2009.
- Krady M.M., Zeng J., Yu J., MacLauchlan S, Skokos E.A., Bornstein P., Sessa W.C., Kyriakides T.R. Thrombospondin-2 modulates extracellular matrix remodeling during physiologic angiogenesis. American Journal of Pathology 173:879-91. 2008
- Jay, S.M., Skokos, E., Laiwalla, F., Krady, M.M., Kyriakides, T.R. Foreign Body Giant Cell Formation Is Preceded by Lamellipodia Formation and Can Be Attenuated by Inhibition of Rac1 Activation. American Journal of Pathology, 171: 2, 2007.