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 过去二十年的研究导致发现了导致罕见自体炎症的突变 并加深了我们对常见自身免疫性疾病的理解。此外，对 自体炎症和自身免疫性疾病背后的复杂机制也在迅速扩大 佩斯。我们现在对先天和适应性关键组件之间的相互作用有了更好的理解 免疫系统和涉及的途径。这些进展是由测序方面的改进推动的 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，以及 分辨率成像。此外，改进的人类疾病动物模型、创新的干细胞和有机化合物 系统，以及对微生物组对免疫反应性影响的新认识，推动了进展。 这些发现提供了一个框架，用于识别新的靶点来治疗广泛的自身免疫和 炎症性疾病。尽管取得了这些进展，但免疫介导的疾病正在达到流行的程度。 为了解决这一新出现的健康危机，我们必须培养下一代科学家，以利用这些 对自体炎症和自身免疫性疾病的洞察和开发新的治疗策略。 自身免疫和自体炎症分子基础(AATG)T32的培训为博士后做准备 通过提供坚实的先天和先天基本原理的基础，使学生成为未来的科学领袖 适应性免疫。AATG项目汇集了来自10个部门的34名调查人员，代表着 广泛的研究背景和专业知识，从基础研究到药物发现，他们是 从事以自身免疫/自体炎症为重点的基础性和转化性疾病研究 条件。 具有挑战性 我们的教职员工都是各自领域中当前或后起之秀的领导者，这将培养他们的智力。 论述，对切割原理和应用的坚定理解和工作知识- 前沿研究技术，激动人心的论文研究。我们的目标是为我们的实习生提供以下技能 在不断发展的生物医学研究世界中，作为独立和创造性的研究人员取得成功。 AATG为博士生提供关键的职业技能，以便有效地交流他们的发现， 并将大力鼓励学生参加地区、国家和国际会议。这个 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医生-科学家将使我们的 受训人员与邻近临床站点的领导接触，以更好地了解我们希望治愈的疾病。这个 AATG的教职员工进一步成为榜样，为女性提供有吸引力的机会，在经济上 鼓励弱势群体和代表性不足的少数群体从事基础科学研究。 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。

• DOI: 10.1161/circresaha.123.322867
• 发表时间: 2023
• 期刊: Circulation research
• 影响因子: 20.1
• 作者: Janardhan,HarishP;Jung,Roy;Trivedi,ChinmayM
• 通讯作者: Trivedi,ChinmayM

Unveiling the Spatiotemporal Diversity of the Endothelium in Development: A Multi-Omics Approach.

• DOI: 10.1161/circresaha.124.324328
• 发表时间: 2024-03
• 期刊: Circulation research
• 影响因子: 20.1
• 作者: Roy Jung;Chinmay M. Trivedi

Assessing risk amid uncertainty inside and outside the dermatology clinic.

在皮肤科诊所内外的不确定性中评估风险。

• DOI: 10.1016/j.jaad.2023.06.038
• 发表时间: 2023
• 期刊: Journal of the American Academy of Dermatology
• 影响因子: 13.8
• 作者: Vanderweil,StefanG;Yang,Caroline;Pagani,Kyla;Chuprin,Jane;Bernhard,Jeffrey;Harris,JohnE
• 通讯作者: Harris,JohnE

Rational design of a JAK1-selective siRNA inhibitor for the modulation of autoimmunity in the skin.

• DOI: 10.1038/s41467-023-42714-4
• 发表时间: 2023-11-04
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Tang, Qi;Fakih, Hassan H.;Ul Abideen, Mohammad Zain;Hildebrand, Samuel R.;Afshari, Khashayar;Gross, Katherine Y.;Sousa, Jacquelyn;Maebius, Allison S.;Bartholdy, Christina;Sogaard, Pia Pernille;Jackerott, Malene;Hariharan, Vignesh;Summers, Ashley;Fan, Xueli;Okamura, Ken;Monopoli, Kathryn R.;Cooper, David A.;Echeverria, Dimas;Bramato, Brianna;Mchugh, Nicholas;Furgal, Raymond C.;Dresser, Karen;Winter, Sarah J.;Biscans, Annabelle;Chuprin, Jane;Haddadi, Nazgol-Sadat;Sherman, Shany;Yildiz-Altay, Ummugulsum;Rashighi, Mehdi;Richmond, Jillian M.;Bouix-Peter, Claire;Blanchard, Carine;Clauss, Adam;Alterman, Julia F.;Khvorova, Anastasia;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。

• DOI: 10.1158/1078-0432.ccr-23-0433
• 发表时间: 2024
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Nayyar,Naema;deSauvage,MagaliA;Chuprin,Jane;Sullivan,EmilyM;Singh,Mohini;Torrini,Consuelo;Zhang,BritneyS;Bandyopadhyay,Sushobhana;Daniels,KeithA;Alvarez-Breckenridge,Christopher;Dahal,Ashish;Brehm,MichaelA;Brastianos,Priscil
• 通讯作者: Brastianos,Priscil