AREA IV IMMUNOLOGY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 第四领域，免疫学的目标是了解细胞之间的相互作用和控制 免疫系统的发育和功能。在集团内部，一个较小的小组专注于 在发育和调节层面上调节自身免疫的机制。有六名成员 第四区，由来自纽约州立大学医学院微生物学系的两名研究活跃教师和 免疫学4人，生物系4人。威廉·博托、舒巴·戈文德和曾傑瑞·盖登是通过 RCMI直接授予。马克·佩扎诺在担任过以下职位后，被聘为生物系的教员 他是RCMI项目的副主任，并与盖登博士在研究项目上合作了几年。保罗 Gottlieb和Linda Spatz被纽约州立大学医学院聘用，并被招募加入RCMI项目，因为他们 当免疫学小组在上一年成立时，积极的研究合作专注于自身免疫 求婚。所有这些研究人员目前都有外部资金用于他们的研究项目，其中许多人 在集团内部和与外部调查人员合作的项目。该小组的研究兴趣是多样的，范围很广 从果蝇天然免疫系统发育和功能研究到KSHV在中国的传播和进化 人类。我们有几名研究人员研究B和T细胞中免疫细胞发育的各个方面，并 免疫系统调节，这是免疫学中的一个关键问题，即免疫系统如何 区分自我和非我。这些研究与自身免疫性疾病的发展直接相关。在……里面 在授权期内，我们申请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活动中的临界质量。 研究领域。 2008年秋天，马尔科姆·摩尔博士在纪念斯隆·凯特琳癌症中心的实验室的希琳·萨尔克加入了 免疫组(第四区)。希琳获得了博士学位。来自阿尔伯特·爱因斯坦医学院 纽约。她是波士顿儿童医院斯图尔特·H·奥尔金博士实验室的博士后研究员， 哈佛医学院。作为一名研究生，她研究了免疫球蛋白基因位点的转录调控。她的初选 这项工作总结在两个第一作者J.免疫学手稿中。作为一名博士后研究员，她追求这一角色 被称为GFI(生长因子独立)蛋白的转录抑制物在造血谱系决定和 差异化。她首先专注于GFI-1b基因，并通过基因打靶表明其表达对Red 小鼠的细胞和巨核细胞发育。以此为背景，她接着问道，GFI-1b和 它的相关蛋白GFI-1(在髓系分化中是必不可少的)起作用。为了做到这一点，她在一个 用于显微测序的红系细胞系和纯化蛋白复合体。通过这条路线，她发现共享的N- GFI蛋白的末端SNAG结构域招募一个转录辅助抑制物复合体，包括Corest和 组蛋白去甲基酶LSD-1。通过使用RNAi，她证明了Corest和LSD-1对于正确区分 三种不同的谱系(红血球、巨核细胞和中性粒细胞)和LSD-1的丢失与增加有关 GFI-1b靶基因H3K4甲基化。通过这种方式，她关闭了环路，以揭示GFI蛋白是如何连接的 造血细胞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.