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Role of Tissue Resident Macrophages in Conventional Outflow Function

组织驻留巨噬细胞在常规流出功能中的作用

基本信息

批准号：
10320065
负责人：
Katy C Liu
金额：
$ 17.09万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10320065
关键词：
Ablation Address Adrenal Cortex Hormones Anterior Biological Assay Biological Response Modifiers Biomechanics Biometry Blindness Blood Blood Vessels Bone Marrow CD44 Antigens Cell physiology Cells Collagen Data Development Plans Distal Doctor of Philosophy Educational workshop Endothelium Environment Extracellular Matrix Eye Faculty Fellowship Flow Cytometry Foundations Funding Future Generations Genes Genetic Genetic Transcription Glaucoma Glucocorticoids Goals Grant Homeostasis Human Immune Immune response Immune system Immunologic Factors Immunology Immunomodulators Individual Institution Knowledge Label Lasers Measures Mediating Mentors Mentorship Molecular Monitor Mus Nursing Faculty Ophthalmologist Pathway interactions Patients Phagocytes Pharmacology Phenotype Physiologic Intraocular Pressure Physiology Prostaglandins Publications Regulation Research Resistance Risk Factors Role Scientist Shapes Smooth Muscle Structure of sinus venosus of sclera Synthetic Prostaglandins Teacher Professional Development Testing Therapeutic Time Tissues Trabecular meshwork structure Training Transforming Growth Factor Beta 2 Transforming Growth Factor beta Treatment outcome Veins Work aqueous blind career career development confocal imaging design experience experimental study eye center improved lymphatic vessel macrophage meetings modifiable risk mouse genetics mouse model novel prenatal pressure programs repaired responsible research conduct single-cell RNA sequencing skills therapeutic target tool transcriptome

项目摘要

PROJECT SUMMARY/ABSTRACT Candidate: The candidate, Katy Liu, is an MD/PhD glaucoma fellowship-trained, board-eligible ophthalmologist with a career goal of becoming an independent clinician-scientist. She has a PhD in Cell & Molecular Physiology, and her long-term objective is to better understand the pathobiology of the conventional outflow tract in order to improve treatments and outcomes in patients with glaucoma. Dr. Liu is completing a glaucoma research fellowship and will be promoted to faculty at the Duke Eye Center in July 2020. Career Development Plan: Dr. Liu proposes to investigate the role of tissue resident macrophages in conventional outflow homeostasis, which directly impacts the regulation of intraocular pressure (IOP). The proposed K08 will allow Dr. Liu to expand upon her current scientific knowledge and skills by gaining experience in ocular immunology, aqueous outflow physiology, genetic mouse models, flow cytometry and single-cell RNA sequencing. Dr. Liu will obtain formal didactics in ocular immunology, mouse genetics, biostatistics and responsible conduct of research. She will attend individual meetings with co-mentors to discuss career development, departmental seminars and faculty development workshops. Dr. Liu will regularly attend national meetings to discuss and present ongoing research, and submit her work for publication. Environment: The mentorship team consists of renowned experts in conventional outflow physiology and ocular immunology who are ideal to advise the candidate on her research. The Duke Eye Center is ideal for Dr. Liu with specific strengths in its Glaucoma research program and the Center for Ocular Immunology. She will also benefit from the world-class research and clinical faculty at the Duke Eye Center. Finally, the mentorship team and institution are fully committed to prepare Dr. Liu for independence as an R01-funded scientist. Research: Although immune regulators such as TGF-beta, corticosteroids and prostaglandin analogues are known to alter conventional outflow function, the role of the native immune system in conventional outflow homeostasis is poorly understood. This proposal is designed to test the hypothesis that tissue resident macrophages function in IOP regulation by altering extracellular matrix (ECM) homeostasis in the conventional outflow tract. In Aim 1, macrophages in the outflow tract will be characterized by lineage tracing and their functional effect measured by IOP and outflow facility following pharmacologic depletion or genetic deletion of macrophages. Aim 2 will assess changes to the ECM of the juxtacanalicular trabecular meshwork, the region of greatest outflow resistance generation in the conventional outflow tract, with macrophage deletion by measuring biomechanical stiffness and analyzing ECM components. Aim 2 will also reveal the TM macrophage-specific transcriptome which we will correlate with its functional role in the conventional outflow tract. This project will provide a better understanding of macrophage function in IOP homeostasis, which will influence future therapeutic strategies for glaucoma and serve as the foundation for a future R01 grant.

项目总结/文摘