Training in the Molecular Basis of Autoimmunity and Autoinflammation

自身免疫和自身炎症的分子基础培训

• 批准号: 10712784
• 负责人: Katherine A. Fitzgerald
• 金额: $ 24.34万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712784
• 关键词: Autoimmunity; Molecular; Training; autoinflammation

PROJECT ABSTRACT Research over the past two decades has led to the discovery of mutations that cause rare autoinflammatory diseases and advanced our understanding of common autoimmune diseases. Further, the understanding of the complex mechanisms underlying autoinflammatory and autoimmune diseases has also expanded at a rapid pace. We now have a better understanding of the interplay between key components of innate and adaptive immune systems and the pathways involved. These advances were driven by improvements in sequencing technologies, single-cell genomic approaches, spatial transcriptomics, proteomics, metabolomics, and high- resolution imaging. Additionally, improved animal models of human disease, innovative stem cell and organoid systems, and a new appreciation for the microbiome's influence on immune reactivity have fueled progress. These discoveries provide a framework for identifying new targets to treat a wide range of autoimmune and inflammatory diseases. Despite these advances, immune-mediated diseases are reaching epidemic proportions. To address this emerging health crisis, we must train the next generation of scientists to capitalize on these insights and develop novel therapeutic strategies for autoinflammatory and autoimmune diseases. The Training in the Molecular Basis of Autoimmunity and Autoinflammation (AATG) T32 prepares predoctoral students to become future scientific leaders by providing a strong foundation in the basic principles of innate and adaptive immunity. The AATG program brings together 34 investigators from ten departments, representing a broad spectrum of research backgrounds and expertise, ranging from basic research to drug discovery, who are engaged in basic and translational, disease-oriented research focusing on autoimmune/autoinflammatory conditions. challenging Our faculty are either current or up-and-coming leaders in their fields, which will foster intellectually discourse, a firm understanding and working knowledge of the principles and applications of cutting- edge research technologies, and exciting thesis research. The goal is to provide our trainees with the skill set to succeed as independent and creative investigators in the constantly evolving world of biomedical research. The AATG provides predoctoral students with critical career skills to effectively communicate their discoveries, and students will be strongly encouraged to participate in regional, national and international meetings. The training curriculum will also emphasize scientific rigor, methods for appropriate data management/analysis/ validation, biosafety, conflict resolution, and ethical conduct. The AATG physician-scientists will enable our trainees to engage with leaders in adjacent clinical sites to better understand the diseases we hope to cure. The AATG faculty further serve as role models and provide attractive opportunities for women, economically disadvantaged and underrepresented minorities to encourage the pursuit of careers in basic scientific research. These goals will help meet future challenges and societal needs in biomedical research.

项目摘要 过去二十年的研究发现了导致罕见自身炎症的突变 疾病并增进了我们对常见自身免疫性疾病的了解。此外，对以下内容的理解 自身炎症和自身免疫性疾病的复杂机制也迅速扩展 步伐。我们现在对先天性和适应性的关键组成部分之间的相互作用有了更好的理解 免疫系统和相关途径。这些进步是由测序技术的改进推动的 技术、单细胞基因组方法、空间转录组学、蛋白质组学、代谢组学和高 分辨率成像。此外，改进的人类疾病动物模型、创新的干细胞和类器官 系统以及对微生物组对免疫反应影响的新认识推动了进展。 这些发现为识别治疗各种自身免疫性疾病和疾病的新靶点提供了一个框架。 炎症性疾病。尽管取得了这些进展，免疫介导的疾病仍已达到流行病的程度。 为了解决这一新出现的健康危机，我们必须培训下一代科学家利用这些 洞察并开发针对自身炎症和自身免疫性疾病的新治疗策略。 自身免疫和自身炎症分子基础培训 (AATG) T32 为博士前准备 通过为与生俱来的基本原理打下坚实的基础，使学生成为未来的科学领导者 适应性免疫。 AATG 项目汇集了来自 10 个部门的 34 名研究人员，代表了 广泛的研究背景和专业知识，从基础研究到药物发现， 从事基础和转化、以疾病为导向的研究，重点关注自身免疫/自身炎症 状况。 具有挑战性的 我们的教师要么是各自领域的现任或后起之秀的领导者，这将培养智力 话语，对切割原理和应用的牢固理解和工作知识 前沿研究技术和令人兴奋的论文研究。我们的目标是为我们的学员提供技能 在不断发展的生物医学研究领域中，作为独立且富有创造力的研究者取得成功。 AATG 为博士前学生提供关键的职业技能，以有效地交流他们的发现， 我们将大力鼓励学生参加地区、国家和国际会议。这 培训课程还将强调科学严谨性、适当数据管理/分析/的方法 验证、生物安全、冲突解决和道德行为。 AATG 医师科学家将使我们 学员与邻近临床中心的领导者接触，以更好地了解我们希望治愈的疾病。这 AATG 教师进一步发挥榜样作用，为女性提供有吸引力的机会 弱势群体和代表性不足的少数群体，鼓励从事基础科学研究事业。 这些目标将有助于应对生物医学研究的未来挑战和社会需求。

项目成果

Lymphatic System in Organ Development, Function, and Regeneration.

淋巴系统在器官发育、功能和再生中的作用。

• 发表时间: 2023-04-28
• 影响因子: 20.1
• 作者: Janardhan, Harish P;Jung, Roy;Trivedi, Chinmay M
• 通讯作者: Trivedi, Chinmay M

Targeting STING oligomerization with small-molecule inhibitors.

使用小分子抑制剂靶向 STING 寡聚化。

• 发表时间: 2023-08-15
• 影响因子: 11.1
• 作者: Humphries, Fiachra;Shmuel;Jiang, Zhaozhao;Zhou, Jeffrey Y;Barasa, Leonard;Mondal, Santanu;Wilson, Ruth;Sultana, Nadia;Shaffer, Scott A;Ng, Sze;Pesiridis, G Scott;Thompson, Paul R;Fitzgerald, Katherine A
• 通讯作者: Fitzgerald, Katherine A

Caenorhabditis elegans in high-throughput screens for anti-infective compounds.

秀丽隐杆线虫抗感染化合物的高通量筛选。

• DOI: 10.1016/j.coi.2018.06.003
• 发表时间: 2018-10
• 期刊: Current opinion in immunology
• 影响因子: 7
• 作者: Peterson ND;Pukkila-Worley R
• 通讯作者: Pukkila-Worley R

T-cell positioning by chemokines in autoimmune skin diseases.

自身免疫性皮肤病中趋化因子对 T 细胞的定位。

• 发表时间: 2019-05
• 影响因子: 8.7
• 作者: Richmond, Jillian M;Strassner, James P;Essien, Kingsley I;Harris, John E
• 通讯作者: Harris, John E

CDK4/6 Inhibition Sensitizes Intracranial Tumors to PD-1 Blockade in Preclinical Models of Brain Metastasis.

在脑转移的临床前模型中，CDK4/6 抑制使颅内肿瘤对 PD-1 阻断敏感。

• 发表时间: 2024-01-17
• 作者: Nayyar, Naema;de Sauvage, Magali A;Chuprin, Jane;Sullivan, Emily M;Singh, Mohini;Torrini, Consuelo;Zhang, Britney S;Bandyopadhyay, Sushobhana;Daniels, Keith A;Alvarez;Dahal, Ashish;Brehm, Michael A;Brastianos, Priscil
• 通讯作者: Brastianos, Priscil