AREA IV IMMUNOLOGY

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 区域IV，免疫学的目标是了解细胞与细胞的相互作用和控制免疫的分子机制。 免疫系统的发展和功能。 在该小组内，一个较小的分组侧重于 调节自身免疫的机制，在发育和调节水平。 有六名成员， 第四区，由来自纽约市立大学医学院微生物学系的2名研究活跃的教师组成， 免疫学4名，生物学4名。 William Boto，Shubha Govind和Jerry Guyden是通过 RCMI直接授予。Mark Pezzano在担任生物学系的教师职位后， RCMI项目副主任，与Guyden博士合作研究项目数年。 保罗 戈特利布和琳达斯帕茨被纽约市立大学医学院聘用，并招募加入RCMI计划，因为他们的 当我们在上一个世纪发起免疫学亚组时， 提议 所有这些研究人员目前都有外部资金支持他们的研究项目，其中许多人有合作伙伴关系。 项目内部和外部调查员。 该小组的研究兴趣是多样化的， 从果蝇先天免疫系统发育和功能的研究到KSHV在果蝇中的传播和进化， 人类 我们有几个研究人员研究B和T细胞中免疫细胞发育的各个方面， 免疫系统调节，这是集中在免疫学的一个关键问题，如免疫系统如何 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 在这段拨款期间，我们要求资金聘请一名额外的免疫学家，以增加我们在这一令人兴奋的 研究领域。 2008年秋天，来自纪念斯隆-凯特琳癌症中心马尔科姆摩尔博士实验室的希琳·萨莱克加入了 免疫组（第四区）。 Shireen获得了博士学位。阿尔伯特·爱因斯坦医学院 纽约。 她曾是斯图尔特·H.波士顿儿童医院的Orkin， 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。她的主要 工作总结在两篇第一作者的J. Immunology手稿中。 作为一名博士后研究员， 转录抑制因子称为Gfi（生长因子独立性）蛋白在造血谱系决策， 分化她首先专注于Gfi-1b基因，并通过基因靶向表明，它的表达对红色至关重要。 细胞和巨核细胞的发育。以此为背景，她接着问Gfi-1b和 其相关蛋白Gfi-1（在髓样分化中是必需的）起作用。为了做到这一点，她在一个 红系细胞系和纯化的蛋白质复合物用于微测序。 通过这条路线，她发现，共享的N- Gfi蛋白的末端SNAG结构域募集了包括CoREST的转录辅阻遏物复合物， 组蛋白去甲基化酶LSD-1。利用RNAi，她表明CoREST和LSD-1对于正确分化细胞是至关重要的。 三种不同的谱系（红细胞、巨核细胞和中性粒细胞），LSD-1的丢失与增加的 在Gfi-1b靶基因的H3 K4处的甲基化。通过这种方式，她闭合了环，揭示了Gfi蛋白如何连接 造血细胞中的转录抑制和表观遗传调节。

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.