The role of the tumor suppressor gene NDRG2 in angiogenesis and wound healing

拟议研究项目的目标是在斯坦福大学整形和重建外科分部哈吉实验室为期两年的研究奖学金中，开发基于细胞的治疗方法，激活树突状细胞并击倒肿瘤抑制基因N-myc下游调节基因2(NDRG2)。该项目旨在确定新的治疗策略的特点，以改善肢体畸形的伤口愈合，例如周围血管疾病或糖尿病患者的伤口愈合。根据现有的文献数据和自己在血管生成领域进行的研究，NDRG2似乎是改善组织灌流的新的有效治疗方法的有前途的靶点。我们假设，从激活的单核细胞培养出来的树突状细胞，在药物刺激下(维生素D3或地塞米松)下调NDRG2，释放促血管生成的细胞因子和生长因子。在几个连续的体外实验中建立了激活内皮细胞的基于细胞的策略后，这项技术将被用于在体内诱导创伤模型的大鼠血管生成，该模型是由斯坦福大学Hagey实验室的团队开发的。这种转化性研究方法的最终目标将是临床应用，以改善慢性伤口的愈合。

The goal of the proposed research project is the development of cell-based therapy with activated dendritic cells and knockdown of the tumor suppressor gene N-myc downstream-regulated gene 2 (NDRG2) in a 2-year research fellowship at the Hagey Laboratory of the Division of Plastic and Reconstructive Surgery at Stanford University. The project aims at the characterization of novel therapeutic strategies for improvement of wound healing in malperfused extremities e.g. in patients with peripheral vascular disease (PVD) or diabetes mellitus. Regarding existing literature data and data from self-conducted research endeavors in the field of angiogenesis, NDRG2 appears to be promising target for novel and effective therapies to improve tissue perfusion. We hypothesize that dendritic cells cultivated from activated monocytes, which were pharmacologically stimulated (vitamin-D3 or dexamethasone) in order to down-regulate NDRG2, release pro-angiogenic cytokines and growth factors. After establishment of the cell-based strategy in several consecutive in vitro experiments for activation of endothelial cells, this technique will be used for induction of in vivo angiogenesis in a wound model in rats which has been developed by the group at the Hagey Laboratory at Stanford University. The final goal of this translational research approach will be a clinical application for the improvement of healing of chronic wounds.