Themis Kyriakides, PhD
Research & Publications
Biography
News
Locations
Research Summary
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 regenerative medicine applications. 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 and hydrogels. Based on our recent findings in genetically modified mice, we have developed a concept that involves exploiting the biology of thrombospodin-2 to improve diabetic wound healing. 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.
Coauthors
Research Interests
Cell Fusion; Education, Medical; Extracellular Matrix; Foreign Bodies; Inflammation; Pathology; Wound Healing; Animal Experimentation; Nanomedicine; Translational Medical Research
Research Image
Focused Ion Beam analysis of cell-nanopattern interactions.
Selected Publications
- An in situ collagen-HA hydrogel system promotes survival and preserves the proangiogenic secretion of hiPSC-derived vascular smooth muscle cells.Dash BC, Duan K, Xing H, Kyriakides TR, Hsia HC. An in situ collagen-HA hydrogel system promotes survival and preserves the proangiogenic secretion of hiPSC-derived vascular smooth muscle cells. Biotechnology And Bioengineering 2020, 117:3912-3923.
- Elevated Thrombospondin 2 Contributes to Delayed Wound Healing in Diabetes.Kunkemoeller B, Bancroft T, Xing H, Morris AH, Luciano AK, Wu J, Fernandez-Hernando C, Kyriakides TR. Elevated Thrombospondin 2 Contributes to Delayed Wound Healing in Diabetes. Diabetes 2019, 68:2016-2023.
- Thrombospondin-2 regulates extracellular matrix production, LOX levels, and cross-linking via downregulation of miR-29.Calabro NE, Barrett A, Chamorro-Jorganes A, Tam S, Kristofik NJ, Xing H, Loye AM, Sessa WC, Hansen K, Kyriakides TR. Thrombospondin-2 regulates extracellular matrix production, LOX levels, and cross-linking via downregulation of miR-29. Matrix Biology : Journal Of The International Society For Matrix Biology 2019, 82:71-85.
- Decellularized materials derived from TSP2-KO mice promote enhanced neovascularization and integration in diabetic wounds.Morris AH, Stamer DK, Kunkemoeller B, Chang J, Xing H, Kyriakides TR. Decellularized materials derived from TSP2-KO mice promote enhanced neovascularization and integration in diabetic wounds. Biomaterials 2018, 169:61-71.
- Regulation of Mesenchymal Stem Cell Differentiation by Nanopatterning of Bulk Metallic Glass.Loye AM, Kinser ER, Bensouda S, Shayan M, Davis R, Wang R, Chen Z, Schwarz UD, Schroers J, Kyriakides TR. Regulation of Mesenchymal Stem Cell Differentiation by Nanopatterning of Bulk Metallic Glass. Scientific Reports 2018, 8:8758.
- Tunable Hydrogels Derived from Genetically Engineered Extracellular Matrix Accelerate Diabetic Wound Healing.Morris AH, Lee H, Xing H, Stamer DK, Tan M, Kyriakides TR. Tunable Hydrogels Derived from Genetically Engineered Extracellular Matrix Accelerate Diabetic Wound Healing. ACS Applied Materials & Interfaces 2018, 10:41892-41901.
- A hidden structural vulnerability in the thrombospondin-2 deficient aorta increases the propensity to intramural delamination.Bellini C, Kristofik NJ, Bersi MR, Kyriakides TR, Humphrey JD. A hidden structural vulnerability in the thrombospondin-2 deficient aorta increases the propensity to intramural delamination. Journal Of The Mechanical Behavior Of Biomedical Materials 2017, 71:397-406.
- Improving in vivo outcomes of decellularized vascular grafts via incorporation of a novel extracellular matrix.Kristofik NJ, Qin L, Calabro NE, Dimitrievska S, Li G, Tellides G, Niklason LE, Kyriakides TR. Improving in vivo outcomes of decellularized vascular grafts via incorporation of a novel extracellular matrix. Biomaterials 2017, 141:63-73.
- Nanopatterned Bulk Metallic Glass Biosensors.Kinser ER, Padmanabhan J, Yu R, Corona SL, Li J, Vaddiraju S, Legassey A, Loye A, Balestrini J, Solly DA, Schroers J, Taylor AD, Papadimitrakopoulos F, Herzog RI, Kyriakides TR. Nanopatterned Bulk Metallic Glass Biosensors. ACS Sensors 2017, 2:1779-1787.
- The host response to naturally-derived extracellular matrix biomaterials.Morris AH, Stamer DK, Kyriakides TR. The host response to naturally-derived extracellular matrix biomaterials. Seminars In Immunology 2017, 29:72-91.
- Nanoparticle delivery of miR-223 to attenuate macrophage fusion.Moore LB, Sawyer AJ, Saucier-Sawyer J, Saltzman WM, Kyriakides TR. Nanoparticle delivery of miR-223 to attenuate macrophage fusion. Biomaterials 2016, 89:127-35.
- Impaired von Willebrand factor adhesion and platelet response in thrombospondin-2 knockout mice.Kristofik N, Calabro NE, Tian W, Meng A, MacLauchlan S, Wang Y, Breuer CK, Tellides G, Niklason LE, Kyriakides TR. Impaired von Willebrand factor adhesion and platelet response in thrombospondin-2 knockout mice. Blood 2016, 128:1642-50.
- Cryopreserved human amniotic membrane and a bioinspired underwater adhesive to seal and promote healing of iatrogenic fetal membrane defect sites.Papanna R, Mann LK, Tseng SC, Stewart RJ, Kaur SS, Swindle MM, Kyriakides TR, Tatevian N, Moise KJ. Cryopreserved human amniotic membrane and a bioinspired underwater adhesive to seal and promote healing of iatrogenic fetal membrane defect sites. Placenta 2015, 36:888-94.
- Engineering cellular response using nanopatterned bulk metallic glass.Padmanabhan J, Kinser ER, Stalter MA, Duncan-Lewis C, Balestrini JL, Sawyer AJ, Schroers J, Kyriakides TR. Engineering cellular response using nanopatterned bulk metallic glass. ACS Nano 2014, 8:4366-75.
- Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response.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. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108:20095-100.
- The CC chemokine ligand, CCL2/MCP1, participates in macrophage fusion and foreign body giant cell formation.Kyriakides TR, Foster MJ, Keeney GE, Tsai A, Giachelli CM, Clark-Lewis I, Rollins BJ, Bornstein P. The CC chemokine ligand, CCL2/MCP1, participates in macrophage fusion and foreign body giant cell formation. The American Journal Of Pathology 2004, 165:2157-66.
- Regulation of angiogenesis and matrix remodeling by localized, matrix-mediated antisense gene delivery.Kyriakides TR, Hartzel T, Huynh G, Bornstein P. Regulation of angiogenesis and matrix remodeling by localized, matrix-mediated antisense gene delivery. Molecular Therapy : The Journal Of The American Society Of Gene Therapy 2001, 3:842-9.
- A mouse knock-in model exposes sequential proteolytic pathways that regulate p27Kip1 in G1 and S phase.Malek NP, Sundberg H, McGrew S, Nakayama K, Kyriakides TR, Roberts JM. A mouse knock-in model exposes sequential proteolytic pathways that regulate p27Kip1 in G1 and S phase. Nature 2001, 413:323-7.
- Matricellular proteins as modulators of cell-matrix interactions: adhesive defect in thrombospondin 2-null fibroblasts is a consequence of increased levels of matrix metalloproteinase-2.Yang Z, Kyriakides TR, Bornstein P. Matricellular proteins as modulators of cell-matrix interactions: adhesive defect in thrombospondin 2-null fibroblasts is a consequence of increased levels of matrix metalloproteinase-2. Molecular Biology Of The Cell 2000, 11:3353-64.
- Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis.Bornstein P, Kyriakides TR, Yang Z, Armstrong LC, Birk DE. Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis. The Journal Of Investigative Dermatology. Symposium Proceedings / The Society For Investigative Dermatology, Inc. [and] European Society For Dermatological Research 2000, 5:61-6.
- Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity.Kyriakides TR, Leach KJ, Hoffman AS, Ratner BD, Bornstein P. Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96:4449-54.
- Accelerated wound healing in mice with a disruption of the thrombospondin 2 gene.Kyriakides TR, Tam JW, Bornstein P. Accelerated wound healing in mice with a disruption of the thrombospondin 2 gene. The Journal Of Investigative Dermatology 1999, 113:782-7.
- Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis.Kyriakides TR, Zhu YH, Smith LT, Bain SD, Yang Z, Lin MT, Danielson KG, Iozzo RV, LaMarca M, McKinney CE, Ginns EI, Bornstein P. Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis. The Journal Of Cell Biology 1998, 140:419-30.
- Compromised production of extracellular matrix in mice lacking secreted protein, acidic and rich in cysteine (SPARC) leads to a reduced foreign body reaction to implanted biomaterials.Puolakkainen P, Bradshaw AD, Kyriakides TR, Reed M, Brekken R, Wight T, Bornstein P, Ratner B, Sage EH. Compromised production of extracellular matrix in mice lacking secreted protein, acidic and rich in cysteine (SPARC) leads to a reduced foreign body reaction to implanted biomaterials. The American Journal Of Pathology 2003, 162:627-35.
- The role of extracellular matrix in the pathophysiology of diabetic wounds.Huang Y, Kyriakides TR. The role of extracellular matrix in the pathophysiology of diabetic wounds. Matrix Biology Plus 2020, 6-7:100037.
- Biocompatibility of nanomaterials and their immunological properties.Kyriakides TR, Raj A, Tseng TH, Xiao H, Nguyen R, Mohammed FS, Halder SS, Xu M, Wu MJ, Bao S, Sheu WC. Biocompatibility of nanomaterials and their immunological properties. Biomedical Materials (Bristol, England) 2021.
- Loss of endothelial glucocorticoid receptor promotes angiogenesis via upregulation of Wnt/β-catenin pathway.Liu B, Zhou H, Zhang T, Gao X, Tao B, Xing H, Zhuang Z, Dardik A, Kyriakides TR, Goodwin JE. Loss of endothelial glucocorticoid receptor promotes angiogenesis via upregulation of Wnt/β-catenin pathway. Angiogenesis 2021.