Cell Fusion; Education, Medical; Extracellular Matrix; Foreign Bodies; Inflammation; Pathology; Wound Healing; Animal Experimentation; Nanomedicine; Translational Medical Research
The main area of my research is the elucidation of the molecular events that dictate the course of healing and especially inflammation and angiogenesis following ischemia, injury and the implantation of biomaterials and scaffolds for tissue engineering applications. In collaboration with VBT colleagues we are exploring the inter-relationship between TSP2 and the Akt/eNOS signaling axis in arteriogenesis. In addition, through the process of molecular dissection of cell-matrix interactions, we aim to incorporate rational design in the development of bioengineering applications such as tissue-engineered vascular grafts. Finally, we aim to define the role of substrate nanotopography in matrix assembly and the regulation of cell-matrix interactions. Recently, we have explored the role of TSP2 in matrix assembly and have shown that the lossof TSP2 results in reduced interation with von Willebrand factor, which provides an explanation for the bleeding diathesis in TSP2 KO mice. We have also initiated studies to investigate the role of TSP2 in diabetic wound healing. In our biomedical engineering-related research we have discovered that mir-223 regulates macrophage fusion in foreign body giant cell formation and have developed a nanoparticle-based strategy to ameliorate this process on the surface of biomaterials. Finally, we have expanded our biomaterial studies to include bulk metallic glass-based implants and have explored the impact of nanotopography on cell function.
Specialized Terms: Angiogenesis; Extracellular matrix remodeling; Inflammation; Cell fusion; Wound healing; Foreign body response; Tissue Engineering, Biomaterials; Nanomaterials; Bulk Metallic Glass
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 engineering 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.