Molecular Mechanisms of Familial Hemophagocytic Lymphohistiocytosis

家族性噬血细胞性淋巴组织细胞增多症的分子机制

• 批准号: 8745493
• 负责人: Helen Su
• 金额: $ 6.74万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8745493
• 关键词: Autologous; Biopsy; Candidate Disease Gene; Cells; Child; Chronic; Cytoplasmic Granules; Cytotoxic T-Lymphocytes; Diagnosis; Disease; Evaluation; Future; Gene Mutation; Gene Targeting; Genes; Goals; Hematopoietic stem cells; Hemophagocytic Lymphohistiocytoses; Immune; Immune response; Immunologic Deficiency Syndromes; In Vitro; Inherited; Knowledge; Lymphocyte; Lymphocyte Function; Lysosomes; Macrophage Activation; Membrane; Molecular; Molecular Target; Mutation; Pathogenesis; Patients; Pluripotent Stem Cells; Proteins; Research; Sampling; Skin; Syndrome; T-Lymphocyte and Natural Killer Cell; Testing; Transplant Recipients; Virus Diseases; clinical decision-making; congenital immunodeficiency; cytotoxic; drug development; exome sequencing; familial hemophagocytic lymphohistiocytosis; healthy volunteer; immune function; improved; induced pluripotent stem cell; keratinocyte; killings; novel; novel therapeutic intervention; preclinical study; tool

In 2013, we continued to accrue several new FHLH and MAS patients to our study, after validating their lack of known mutations and the normal expression of various candidate genes. While continuing to accrue additional patients, we have initiated exome sequencing on these samples, with the goal of identifying new mutations responsible for disease. We have obtained a partial list of candidate genes, which we are have begun to winnow down by functional evaluations in vitro. In parallel, we have also prepared keratinocyte cultures from skin biopsies to improve the efficiency of generating induced pluripotent stem cells from normal healthy volunteers and patients.

2013年，在证实了他们缺乏已知突变和各种候选基因的正常表达后，我们继续将几名新的FHLH和MAS患者纳入我们的研究。在继续增加患者的同时，我们已经对这些样本启动了外显子组测序，目的是识别导致疾病的新突变。我们已经获得了候选基因的部分清单，我们已经开始通过体外功能评估来筛选这些候选基因。与此同时，我们还从皮肤活检组织中制备了角质形成细胞培养物，以提高从正常健康志愿者和患者身上产生诱导多能干细胞的效率。