权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Elucidating mechanisms of checkpoint inhibitor-induced diabetes

阐明检查点抑制剂诱发糖尿病的机制

基本信息

批准号：
10723194
负责人：
Ana Luisa Jordao Perdigoto
金额：
$ 17.35万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-18 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10723194
关键词：
Address Adrenal Glands Adverse event Advisory Committees Affect Antigens Area Authorization documentation Autoantigens Autoimmune Autoimmunity Beta Cell Bioinformatics CTLA4 gene Cancer Patient Cell Communication Cells Clinical Coculture Techniques Collaborations Complication Development Development Plans Diabetes Mellitus Diagnostic Endocrine Endocrine Glands Endocrinologist Endocrinology Environment Event Exocrine pancreas Extramural Activities Fatality rate Fellowship Gene Expression Genetic Transcription Goals Grant Human Immune Immune Targeting Immune Tolerance Immune checkpoint inhibitor Immune response Immunohistochemistry Immunologist Immunology Immunooncology Immunotherapy In Vitro Inbred NOD Mice Inflammation Mediators Insulin-Dependent Diabetes Mellitus Islet Cell Islets of Langerhans Kinetics Knowledge Lead Ligands Malignant Neoplasms Mentorship Modeling Monoclonal Antibodies Morbidity - disease rate Mus Nature Non obese Organ Pancreas Pathogenesis Patients Phenotype Physicians Pituitary Gland Principal Investigator Productivity Reaction Research Research Personnel Resources Role Scientist Self Tolerance Stains Structure of beta Cell of islet T cell clonality T cell receptor repertoire sequencing T cell response T-Cell Receptor T-Lymphocyte Testing Therapeutic Thyroid Gland Time Tissues Training Universities Work anti-PD-L1 anti-PD-L1 therapy anti-tumor immune response authority biomarker discovery biomarker identification body system cancer therapy career development collaborative environment diabetic experience genomic data immune cell infiltrate immune-related adverse events improved islet medical schools mortality mouse genetics mouse model neoplastic cell novel post-doctoral training prevent programmed cell death ligand 1 programmed cell death protein 1 receptor response single-cell RNA sequencing skills targeted treatment therapeutic target therapy development tool translational study tumor tumor growth tumor progression validation studies

项目摘要

Abstract: This K08 proposal will expedite the principal investigator’s progress towards her goal of becoming an independent physician-scientist with a focus on increasing our understanding of mechanisms of immune related adverse events (irAEs) induced by checkpoint inhibitor (CPI) immunotherapies and identifying therapeutic targets of these complications. Candidate: Dr. Ana Perdigoto is a physician-scientist at Yale University School of Medicine. She completed clinical fellowship in Endocrinology and postdoctoral training in Immunology. She is developing an expertise at the crossroads of immuno-endocrinology and immuno- oncology through her work on investigating mechanisms of CPI-induced diabetes (CPI-DM), a complication that arises in cancer patients treated with immunotherapies targeting checkpoint inhibitors. Under the mentorship of Dr. Kevan Herold, a world-renowned Endocrinologist and Immunologist with authority on the immunology of type 1 diabetes and CPI-DM, Dr. Perdigoto investigated how immune cells modify pancreatic islets to cause CPI-DM. She will leverage the skills gained during her training to further analyze mechanisms of these irAEs. Career Development Plan: Dr. Perdigoto will pursue the research in this proposal under the primary mentorship of Dr. Herold. She will also have the guidance of an intramural and extramural advisory team with various areas of expertise and experience in nurturing independent investigators. Yale University provides a collaborative environment with state-of-the-art facilities and resources and excellent training environment and opportunities. The proposed 5-year plan builds on Dr. Perdigoto’s prior experience and further enriches her training to provide the tools needed for establishing independence, such as proficiency in bioinformatics and analysis of genomic data, knowledge in mouse genetics, and productive collaborations. Research Plan: The overall premises addressed in this proposal are that interactions of immune and islet cells in the tissue microenvironment lead to the development of CPI-DM (investigated in Specific Aim 1) and that tumor can impact autoimmunity, potentially through presentation of shared antigens (investigated in Specific Aim 2). Upon completion of the research proposed, Dr. Perdigoto will be able to: 1) characterize immune-target cell interactions that lead to autoimmunity 2) analyze novel tumor models with regards to the impact of immunotherapies and tumor on autoimmunity and 3) identify potential therapeutic targets to prevent adverse events without impacting tumor responses. The findings will enhance our understanding of the pathogenesis of CPI-DM as well as other irAEs arising from CPI treatment. After completing the proposed training, Dr. Perdigoto will have acquired the expertise required to become an independent investigator poised to continue translational studies that can lead to the development of diagnostic or therapeutic tools to protect target cells from the effects of inflammatory mediators both in the field of immuno-oncology and potentially autoimmunity.

文摘: