AREA IV IMMUNOLOGY

IV 区免疫学

• 批准号: 7959167
• 负责人: MARK PEZZANO
• 金额: $ 36.24万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959167
• 关键词: Affinity; Area; Autoimmune Diseases; Autoimmunity; Biology; Boston; Cell Communication; Cell Line; Cells; Cellular Immunology; Collaborations; Complex; Computer Retrieval of Information on Scientific Projects Database; Computer Systems Development; Development; Doctor of Philosophy; Drosophila genus; Epigenetic Process; Erythrocytes; Erythroid Cells; Evolution; Faculty; Funding; GFI1B gene; Gene Targeting; Genes; Goals; Grant; Growth Factor; Hematopoietic; Histones; Human; Human Herpesvirus 8; Immune; Immune system; Immunologist; Immunology; Institution; Interest Group; Laboratories; Manuscripts; Medicine; Memorial Sloan-Kettering Cancer Center; Methylation; Microbiology; Molecular; Mus; Myelogenous; N-terminal; New York; Pediatric Hospitals; Positioning Attribute; Postdoctoral Fellow; Proteins; RNA Interference; Recruitment Activity; Regulation; Research; Research Personnel; Research Project Grants; Resources; Role; Route; Source; Subgroup; T-Lymphocyte; Transcription Repressor/Corepressor; Transcriptional Regulation; United States National Institutes of Health; Work; base; college; falls; gene repression; graduate student; human GFI1B protein; link protein; medical schools; member; neutrophil; programs; protein complex; research and development; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of Area IV, Immunology, is to understand the cell-to-cell interactions and molecular mechanisms that control the development and function of the immune system. Within the group, a smaller subgroup is focused on the mechanisms that regulate autoimmunity, both at the developmental and regulatory levels. There are six members of Area IV, consisting of 2 research active faculty from the CUNY Medical School department of Microbiology and Immunology and 4 from the department of Biology. William Boto, Shubha Govind and Jerry Guyden were hired through the RCMI grant directly. Mark Pezzano was recruited for a faculty position in the Biology department, after serving as Deputy Director of the RCMI program and collaborating on research projects with Dr. Guyden for several years. Paul Gottlieb and Linda Spatz were hired by the CUNY Medical School and recruited to join the RCMI program because of their active research collaboration focused on autoimmunity when the immunology subgroup was initiated in our last proposal. All of these researchers currently have outside funding for their research projects and many have collaborative projects both within the group and with outside investigators. The research interests of the group are diverse, ranging from studies of innate immune system development and function in Drosophila to KSHV transmission and evolution in humans. We have several investigators who study aspects of immune cell development in both B and T cells and immune system regulation, which are focused on a key question in Immunology as to how the immune system distinguishes self from non-self. These studies are directly relevant to the development of autoimmune diseases. In this granting period, we requested funds to hire one additional immunologist to increase our critical mass in this exciting area of research. In the Fall of 2008, Shireen Saleque from Dr. Malcolm Moore's lab at Memorial Sloan Kettering Cancer Center, joined the Immunology group (Area IV). Shireen received her PhD. from Albert Einstein College of Medicine in New York. She was a postdoctoral fellow in the laboratory of Dr. Stuart H. Orkin at Children's Hospital Boston and Harvard Medical School. As a graduate student, she studied transcriptional regulation of the IgH gene locus. Her primary work was summarized in two first-authored J. Immunology manuscripts. As a post- doctoral fellow she pursued the role of transcriptional repressors known as Gfi (growth factor independence) proteins in hematopoietic lineage decisions and differentiation. She focused first on the Gfi-1b gene and showed by gene targeting that its expression is essential for red cell and megakaryocytic development in the mouse. With this as a background she then went on to ask how Gfi-1b and its related protein Gfi-1 (which is essential in myeloid differentiation) act. To do this she affinity-tagged Gfi-1b in an erythroid cell line and purified protein complexes for microsequencing. By this route she discovered that the shared N- terminal SNAG domain of the Gfi proteins recruits a transcriptional corepressor complex including CoREST and the histone demethylase LSD-1. Using RNAi she showed that both CoREST and LSD-1 are critical for proper differentiation of three different lineages (red, megakaryocytic and neutrophil) and that loss of LSD-1 is associated with increased methylation at H3K4 at Gfi-1b target genes. In this manner she closed the loop to reveal how Gfi proteins link transcriptional repression and epigenetic regulation in hematopoietic cells.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 第四区免疫学的目标是了解细胞间的相互作用和控制的分子机制 免疫系统的发育和功能。 在该组内，有一个较小的子组专注于 在发育和调节水平上调节自身免疫的机制。 有六名成员 IV 区，由来自纽约市立大学医学院微生物学系的 2 名研究活跃教师组成 免疫学和生物系 4 名。 William Boto、Shubha Govind 和 Jerry Guyden 是通过 RCMI 直接拨款。马克·佩扎诺 (Mark Pezzano) 在担任生物系教授后被聘为生物系教员。 RCMI 项目副主任，与 Guyden 博士合作研究项目多年。 保罗 Gottlieb 和 Linda Spatz 被纽约市立大学医学院聘用，并被招募加入 RCMI 项目，因为他们的 当我们去年启动免疫学小组时，积极的研究合作集中于自身免疫 提议。 所有这些研究人员目前的研究项目都有外部资助，而且许多研究人员都有合作 小组内部和外部研究人员的项目。 该小组的研究兴趣广泛， 从果蝇先天免疫系统发育和功能的研究到 KSHV 的传播和进化 人类。 我们有几位研究人员研究 B 细胞和 T 细胞中免疫细胞发育的各个方面， 免疫系统调节，重点关注免疫学中的一个关键问题，即免疫系统如何 区分自我与非自我。 这些研究与自身免疫性疾病的发展直接相关。 在 在此资助期间，我们请求资金聘请一名额外的免疫学家，以增加我们在这一激动人心的项目中的临界质量 研究领域。 2008 年秋天，纪念斯隆·凯特琳癌症中心 Malcolm Moore 博士实验室的 Shireen Saleque 加入了 免疫学组（第四区）。 希琳获得博士学位。来自阿尔伯特·爱因斯坦医学院 纽约。 她是波士顿儿童医院 Stuart H. Orkin 博士实验室的博士后研究员， 哈佛医学院。作为一名研究生，她研究了 IgH 基因位点的转录调控。她的小学 两篇第一作者的 J.Immunology 手稿对这项工作进行了总结。 作为一名博士后研究员，她追求这个角色 被称为 Gfi（生长因子独立性）蛋白的转录抑制蛋白在造血谱系决策中的作用 差异化。她首先关注了 Gfi-1b 基因，并通过基因打靶表明，该基因的表达对于红色基因至关重要。 小鼠细胞和巨核细胞的发育。以此为背景，她接着询问 Gfi-1b 和 其相关蛋白 Gfi-1（在骨髓分化中至关重要）发挥作用。为了做到这一点，她在一个 用于微测序的红细胞系和纯化的蛋白质复合物。 通过这条路线，她发现共享的 N- Gfi 蛋白的末端 SNAG 结构域招募转录辅阻遏物复合物，包括 CoREST 和 组蛋白去甲基化酶LSD-1。她利用 RNAi 证明 CoREST 和 LSD-1 对于正确分化 三种不同的谱系（红色、巨核细胞和中性粒细胞），LSD-1 的缺失与增加 Gfi-1b 靶基因 H3K4 甲基化。通过这种方式，她关闭了循环，揭示了 Gfi 蛋白如何连接 造血细胞的转录抑制和表观遗传调控。