Contributio of a novel developmentally-restricted hematopoietic stem cell

新型发育受限造血干细胞的贡献

• 批准号: 9316702
• 负责人: Anna E. Beaudin
• 金额: $ 17.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, MERCED
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9316702
• 关键词: Adult; Affect; Autoimmune Diseases; Autoimmune Process; Autoimmunity; B-Lymphocytes; Biological Response Modifiers; Cell surface; Cells; Cellular biology; Code; Collaborations; Data; Development; Disease; Disease susceptibility; Early Intervention; Epidemiology; Excision; Fetal Development; Gene Expression; Generations; Genetic; Goals; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Immune; Immune System Diseases; Immune Tolerance; Immune system; Immunity; Immunoglobulins; Immunology; Infection; Institutes; Label; Laboratories; Life; Lymphocyte; Lymphoid; Lymphoid Cell; Mediating; Mentors; Modeling; Molecular; Molecular Biology; Natural Immunity; Neonatal; Nutritional Science; Pathologic; Perinatal; Phenotype; Play; Population; Populations at Risk; Predisposition; Prevention; Production; Property; Research; Role; San Francisco; Self Tolerance; Stem cells; T-Lymphocyte; Testing; Tomatoes; Training; Vaccination; Work; base; fetal; genome-wide; immune activation; immune function; innovation; interest; mouse model; novel; post-doctoral training; programs; response; stem; stem cell biology

PROJECT SUMMARY/ABSTRACT The concept of a layered immune system entails the generation of specific functional components of the immune system at different stages of development. Despite three decades of research, the cellular mechanisms underlying immune layering have remained elusive. Our lab recently identified the cellular mechanism contributing to immune layering. Using a lineage tracing mouse model thoroughly characterized in our laboratory, we discovered a developmentally limited hematopoietic stem (HSC) that gives rise to developmentally restricted innate-like immune cells. These innate-like immune cells are critical mediators of immune tolerance and autoimmunity. Building on this discovery, my research interests focus on determining the developmental mechanisms underlying the establishment of immune tolerance and autoimmune susceptibility. I aim to define the unique function of this novel hematopoietic stem cell population in establishing innate immunity during development. I then seek to define the specific phenotypic, functional, and genetic attribute of immune cells generated from a developmentally-restricted HSC. Lastly, I aim to determine the effect of perinatal immune insult on developmental hematopoiesis, immune development and autoimmune disease susceptibility. This work will be conducted in the Institute for the Biology of Stem Cells at UC Santa Cruz in the lab of Dr. Camilla Forsberg, an expert in hematopoietic stem cell biology. Over the course of my doctoral training in nutritional sciences and my postdoctoral training in hematopoietic stem cell biology, I have gained considerable technical and intellectual breadth in developmental, molecular, and cell biology. My immediate goal is to broaden my training within immunology, including coursework, collaboration with expert immunology labs at UC San Francisco, and guidance by my co-mentor, Dr. Robert Coffman, a renowned expert in innate immunology. My long-term goal is to establish an innovative, independent research program at the interface of development, hematopoiesis and immunology.

项目总结/摘要 分层免疫系统的概念需要产生免疫系统的特定功能组分。 不同发育阶段的免疫系统。尽管经过了三十年的研究， 免疫分层的潜在机制仍然难以捉摸。我们的实验室最近发现了 有助于免疫分层的机制。使用谱系追踪小鼠模型， 在我们的实验室里，我们发现了一种发育受限的造血干细胞（HSC）， 发育受限的先天免疫细胞。这些天生的免疫细胞是免疫系统的关键介质。 免疫耐受和自身免疫。基于这一发现，我的研究兴趣集中在确定 建立免疫耐受和自身免疫的发育机制 易感性我的目标是确定这种新的造血干细胞群体在建立造血干细胞系统中的独特功能。 先天免疫在发育过程中然后，我试图定义特定的表型，功能和遗传 这是从发育受限的HSC产生的免疫细胞的属性。最后，我的目标是确定 围产期免疫损伤对造血、免疫发育及自身免疫影响 疾病易感性这项工作将在加州大学圣塔分校的干细胞生物学研究所进行 克鲁兹在造血干细胞生物学专家卡米拉·福斯伯格博士的实验室里。在我的 营养科学博士培训和造血干细胞生物学博士后培训，我有 在发育、分子和细胞生物学方面获得了相当大的技术和知识广度。我 近期目标是扩大我在免疫学方面的培训，包括课程作业、与专家的合作 免疫学实验室在加州大学旧金山分校弗朗西斯科，并指导我的共同导师，博士罗伯特科夫曼，一个著名的 先天免疫学专家我的长期目标是建立一个创新的，独立的研究计划， 发育、造血和免疫学的界面。