Douglas Losordo's Laboratory Research Group  | Kentaro Jujo, MD
Postdoctoral Fellow
Tokyo, Japan Dr. Jujo is studying the effects of CXCR4 antagonism on the bioactivity of endothelial progenitor cells (EPCs), and the role these effects have on cardiac function following myocardial ischemia-reperfusion injury. His investigation seeks to determine whether disruption of the SDF-1α/CXCR4 axis mobilizes EPCs from the bone marrow, and to characterize the mechanism of any observed improvement in functional recovery after myocardial injury. A specific small molecule CXCR4 antagonist is being investigated in an animal model of myocardial-reperfusion injury. This model closely resembles the clinical setting of myocardial injury because blood flow is interrupted temporarily rather than permanently as in other myocardial injury models. |  | Koichi Kobayashi, MD
Postdoctoral fellow
Nagoya, Japan Dr. Kobayashi is studying cardiogenesis by wnt gene therapy in acute myocardial infarction. His project is designed to determine whether gene therapy with the wnt plasmid enhances recovery from myocardial infarction by inducing the differentiation of progenitor cells into cardiac cells. Progenitor cells are mobilized from the bone marrow in a myocardial infarction model, and wnt gene therapy is introduced locally. Subsequent assessments will identify the presence and lineage of mobilized cells in the ischemic myocardium. |  | Yukihide Nishimura, MD
Postdoctoral Fellow
Kyoto, Japan Dr. Nishimura is evaluating the effect of CXCR4 antagonism on wound healing. His project is designed to determine whether disrupting the interaction between SDF-1α and CXCR4 improves wound healing and alters the bioactivity of endothelial progenitor cells (EPCs) and fibroblasts. In vivo experiments examine the effects of a specific small molecule antagonist of CXCR4 on tissue regeneration in mice with full-thickness excisional skin wounds, and in vitro experiments characterize the proliferation and migration of EPCs and fibroblasts after exposure to the CXCR4 antagonist. |  | Marie-Ange Renault, PhD
Postdoctoral Fellow
Bordeaux, France Dr. Renault is studying the angiogenic activity of sonic hedgehog (Shh) via rho kinase–dependent MMP-9 and osteopontin expression. Her studies are designed to characterize the molecular mechanisms involved in Shh-induced angiogenesis, specifically, the effect of Shh on endothelial cells. In vitro analyses assess the effects of Shh treatment on proliferation, migration, tube formation, and the expression of a variety of pro-angiogenic factors (VEGF, Ang1, βFGF, SDF-1α, MMP-9, osteopontin), and the activation of Gli transcription factors or the Rho signaling pathway. The potential involvement of MMP-9, ostepontin, and the Rho signaling pathway during Shh-induced angiogenesis is being investigated in vivo by implanting pellets containing Shh, a Rho kinase inhibitor, or saline in the corneas of wild-type, MMP-9-null, or osteopontin-null mice. |  | Jerome Roncalli, MD
Postdoctoral Fellow
Toulouse, France Dr. Roncalli is evaluating the effect of combined endothelial progenitor cell (EPC) mobilization and sonic hedgehog (Shh) therapy on cardiac function recovery after acute myocardial infarction. His experiments investigate whether the bioactivity of EPCs and fibroblasts are altered by combining pharmaceutical therapy that increases EPC mobilization (ie., a specific CXCR4 antagonist) with gene therapy that improves EPC recruitment and incorporation (Shh). EPC mobilization and expression of cytokines and growth factors are determined after experimental myocardial infarction in mice. The effects of Shh therapy in vitro are evaluated by measuring cytokine expression in fibroblasts treated with either Shh protein or transfected with Shh plasmid, and by assessing the proliferation, tube formation, and migration of EPCs cultured in conditioned media from treated and untreated fibroblasts. |  | Haruki Sekiguchi, MD
Postdoctoral Fellow
Tokyo, Japan Dr. Sekiguchi is studying the role of neural stem cells, the sonic hedgehog (Shh) pathway, and estradiol during nerve regeneration. Neural stem cells are isolated from mice that constitutively express β-galactosidase or LacZ, and administered with or without estradiol to wild-type mice after experimental nerve crush injury. Assessments include measures of intraneural angiogenesis and motor conduction velocity, and histological identification of labeled cells in regenerating tissues. Differentiation of neural stem cells is assessed by staining labeled cells for expression of endothelial (CD31) cell markers. |  | Toshikazu Tanaka, MD
Postdoctoral Fellow
Tokyo, Japan Dr. Tanaka is evaluating whether mechanisms of β2-agonists regulate stem cell mobilization after myocardial infarction by increasing plasma cytokine levels. His investigation is designed to determine whether certain commonly used medications, β2-agonists, improve recovery from acute myocardial infarction by increasing plasma G-CSF and GM-CSF. Increased levels of these cytokines result in mobilization of endothelial progenitor cells (EPCs) from the bone marrow into the peripheral circulation, thus enhancing recruitment of EPCs to the injured tissue. Experiments are being performed in a mouse model of myocardial infarction. |  | Jorn Tongers, MD
Postdoctoral Fellow
Hannover, Germany Dr. Tongers is evaluating the retention and maintenance of progenitor cells in the ischemic target region by bioactive, self-assembling nanofibers. His project is designed to investigate whether the use of a nanofiber matrix can increase the potency of cell therapy for treatment of ischemic cardiovascular disease by overcoming low retention and low viability of endothelial progenitor cells (EPCs) in ischemic tissue. Experiments are intended to assess EPC proliferation, apoptotosis, adhesion, migration, differentiation, and tube formation when cultured in the presence of nanofibers. Using a hind-limb ischemia model, the influence of nanofibers on cell therapy for tissue regeneration will be assessed in vivo. |
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