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Trans-megakaryocyte migration as neutrophil amplifier

作为中性粒细胞放大器的跨巨核细胞迁移

基本信息

批准号：
10599971
负责人：
Pierre Cunin
金额：
$ 12.73万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10599971
关键词：
Achievement Advisory Committees Amplifiers Animals Appointment Arthritis Autoimmune Diseases Award Biochemistry Bioinformatics Biology Blocking Antibodies Blood Blood Platelets Bone Marrow Bone Marrow Cells Boston Cell Adhesion Molecules Cell Communication Cell Nucleus Cells Cellular Immunology Chemotaxis Circulation Confocal Microscopy Cytoplasm Data Deposition Disease Electron Microscopy Emperipolesis Endothelial Cells Endothelium Ensure Environment Enzyme-Linked Immunosorbent Assay Exhibits Exposure to Faculty Flow Cytometry Frequencies Funding Goals Health Hemostatic function Human Biology Hybrids Imaging Device Immune Immunity Immunology In Vitro Inflammation Inflammatory Institution Interleukin-1 beta International K/BxN model Knowledge Laboratories Large Megakaryocyte Leadership Learning Marrow Mass Spectrum Analysis Mediating Mediator Megakaryocytes Membrane Mentored Research Scientist Development Award Mentors Mentorship Methods Microscopy Modeling Molecular Molecular Biology Mus Myelogenous Neutrophil Activation Operative Surgical Procedures Organ Pathologic Pediatric Hospitals Pediatrics Peritonitis Photons Physiological Plasma Positioning Attribute Process Proteins Reporting Research Research Personnel Research Training Role Route Serum Slide Source Speed Sterility TNF gene Technical Expertise Testing Time Training Transgenic Mice Visualization Work cell behavior eptifibatide exosome immune function immunoregulation in vivo inhibitor instructor intravital imaging intravital microscopy medical schools member migration neutrophil novel septic skills systemic inflammatory response therapeutic target training opportunity transcriptome sequencing two photon microscopy two-photon

项目摘要

Project summary / abstract This K01 award is to provide Dr. Pierre Cunin with the advanced research training, protected time, and mentoring needed to become an independent investigator specialized in intravital 2-photon microscopy and committed to understanding the role of megakaryocytes as a direct modulators of immunity. Candidate: Dr. Cunin is an Instructor in Pediatrics at Harvard Medical School (Boston MA), in the laboratory of Dr. Peter Nigrovic in the Division of Immunology at the Boston Children’s Hospital. Dr Cunin’s previous training has provided him with extensive knowledge in the biology of human and murine immune cells, as well as a technical expertise in cellular immunology, molecular biology, biochemistry, and murine experimentation. Research: Dr. Cunin’s K01 project seeks to understand the function of emperipolesis (EP), a cell-in-cell interaction wherein a neutrophil transits through the cytoplasm of a megakaryocyte. Routinely observed in bone marrow from all species examined, EP had never been investigated in depth experimentally. Dr. Cunin found that EP increases in arthritis and other forms of systemic inflammation, suggesting a role in disease. He previously reported that EP is an active and highly regulated process that mediates bi-directional transfer of proteins and membrane between neutrophils and megakaryocytes. Preliminary data show that this exchange has important physiological consequences for neutrophil function. Dr. Cunin will evaluate how EP modulates the immune function of neutrophils in health and with inflammation. Finally, Dr. Cunin will identify ways to manipulate EP via targets on neutrophil or megakaryocyte, opening up the possibility of therapeutic targeting. Mentoring/Training: The long-term goal of the PI is becoming an independent investigator and tenured faculty member at a leading academic center. The proposed studies and training plan will set the stage for Dr. Cunin to obtain independent R01 funding and become an internationally recognized leader at the cutting-edge of the exploration of megakaryocytes as immune cells, as well as of the pathological role of this lineage in autoimmune and inflammatory diseases. With his appointment as Director of the 2-photon facility in the Division of Immunology at BCH, he will become an expert in intravital imaging to observe immune cells behaviors in their organs, in healthy animals or subjected to inflammation. His research training will encompass in vivo cell visualization and live cell analysis, animal surgery, and bioinformatics for RNA sequencing. Additionally, he will learn laboratory leadership skills to facilitate the transition to his own laboratory. The work will be performed in a superb institutional environment with the mentorship of Dr. Peter Nigrovic, an expert in myeloid biology and inflammatory diseases, Dr. Italiano, an expert in megakaryocyte biology, as well as an Advisory Committee including Drs. Bergmeier and Kim (surgery and in vivo assessment). Guidance on 2- photon technical issues and RNAseq analysis will be provided by collaborators Drs. Chen and Lee.

项目摘要/摘要