Immune Cell Modulation in Laryngotrachael Fibrosis

喉气管纤维化中的免疫细胞调节

基本信息

批准号：
9750678
负责人：
Alexander Hillel
金额：
$ 23.89万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9750678
关键词：
Adult Advanced Development Air Aphonia Biomechanics Biomedical Engineering Biometry Biopsy Blood Vessels Breathing Cells Cicatrix Clinical Clinical Trials Communication Disability Data Development Disease Dysphonia Engineering Environment Enzyme-Linked Immunosorbent Assay Ethics Experimental Designs FRAP1 gene Faculty Fibroblasts Fibrosis Flow Cytometry Functional disorder Future Gene Expression Goals Head and Neck Surgery Histologic Histology Human Immune Immune Targeting Immune response Immunohistochemistry Immunologics Immunology In Situ In Vitro Infant Inflammation Inflammatory Inflammatory Response Injury Institutes Interdisciplinary Study Intervention Intubation Investigation K-Series Research Career Programs Knowledge Larynx Mechanics Medical Medical Research Mentors Mentorship Methodology Methods Modeling Molecular Molecular Biology Mus Otolaryngology Outcome Pathologic Pathologic Processes Patients Pharmaceutical Preparations Phenotype Polymers Process Property Proteins Public Health Schools Pulmonary Fibrosis Regenerative Medicine Research Research Personnel Research Training Resources Risk Role Running Science Secondary to Signal Transduction Sirolimus Stenosis Stents Subglottis structure Surface Surgical Management T-Lymphocyte Techniques Testing Therapeutic Trachea Tracheostomy procedure Tube Voice Wisconsin Wound Healing airway obstruction base biocompatible polymer body system career clinical practice cytokine design endotracheal experience improved in vivo in vivo Model inhibitor/antagonist macrophage materials science medical schools member mortality mouse model novel public health relevance response skills therapeutic target

项目摘要

DESCRIPTION (provided by applicant): Dr. Alexander Hillel is a junior faculty member in the Department of Otolaryngology-Head & Neck Surgery at the Johns Hopkins School of Medicine where his clinical practice is dedicated to the medical and surgical management of voice and airway disorders. With the support of a Mentored Career Development Award, Dr. Hillel seeks to better understand the inflammatory mechanisms of laryngotracheal fibrosis (LTF) and apply regenerative medicine techniques to its treatment. Specifically, Dr. Hillel will be focusing on mammalian target of rapamycin (mTOR), which has been shown to activate the same type of T cells and macrophages in pulmonary fibrosis that has been observed in early models of LTF. Ultimately, he plans to develop a drug-eluting stent to target the immune mechanisms. Aim 1 will characterize the inflammatory response to mechanical injury in the mouse trachea and then determine the role of mTOR in regulating macrophages and T-lymphocytes that precede LTF in a novel in vivo in situ mouse model. Aim 2 will characterize the role of macrophages, T-lymphocytes, and their inflammatory cytokines in patient with and patients at risk for developing LTF. Finally, Aim 2 will focus on identifying an ideal bioabsorbable polymer to engineer a drug-eluting airway stent targeting mechanisms identified in earlier aims. During the course of this proposal, Dr. Hillel will enhance his research knowledge and skills with coursework in immunology, biostatistics, and ethical research, receive directed mentorship by an interdisciplinary team of experienced researchers, and be immersed in the interdisciplinary research and clinical environments of the Johns Hopkins School of Medicine, Johns Hopkins Bloomberg School of Public Health, and the Laryngeal Research Group at The Wisconsin Institute of Medical Research in Madison, Wisconsin. This Career Development Award will provide Dr. Hillel with the resources that he needs to become an independent investigator and future leader in voice science research.

描述（由申请人提供）：Alexander Hillel 博士是约翰·霍普金斯大学医学院耳鼻咽喉头颈外科系的初级教员，他的临床实践致力于语音和气道疾病的内科和外科治疗在导师职业发展奖的支持下，Hillel 博士寻求更好地了解喉气管纤维化 (LTF) 的炎症机制，并将再生医学技术应用于其治疗。 Hillel 博士将重点研究哺乳动物雷帕霉素靶标 (mTOR)，该药物已被证明可以激活与早期 LTF 模型中观察到的相同类型的 T 细胞和巨噬细胞，特别是在肺纤维化中。目标 1 将表征小鼠气管对机械损伤的炎症反应，然后确定 mTOR 在 LTF 之前调节巨噬细胞和 T 淋巴细胞的作用。 Aim 2 将在新型体内原位小鼠模型中表征巨噬细胞、T 淋巴细胞及其炎性细胞因子在 LTF 患者和有风险的患者中的作用。设计早期目标中确定的药物洗脱气道支架靶向机制。在此提案过程中，Hillel 博士将通过免疫学、生物统计学和伦理研究课程提高他的研究知识和技能，并接受指导。由经验丰富的研究人员组成的跨学科团队提供指导，并沉浸在约翰·霍普金斯大学医学院、约翰·霍普金斯大学彭博公共卫生学院和麦迪逊威斯康星医学研究所喉部研究小组的跨学科研究和临床环境中，威斯康星州，该职业发展奖将为 Hillel 博士提供成为语音科学研究的独立研究者和未来领导者所需的资源。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Increased Expression of PD-1 and PD-L1 in Patients With Laryngotracheal Stenosis.

喉气管狭窄患者 PD-1 和 PD-L1 表达增加。

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
Davis, Ruth J;Lina, Ioan;Ding, Dacheng;Engle, Elizabeth L;Taube, Janis;Gelbard, Alexander;Hillel, Alexander T
通讯作者：
Hillel, Alexander T

Inaugural Symposium on Advanced Surgical Techniques in Adult Airway Reconstruction: Proceedings of the North American Airway Collaborative (NoAAC).

首届成人气道重建先进外科技术研讨会：北美气道合作组织 (NoAAC) 会议记录。

DOI：
发表时间：
2017-06-01
期刊：
影响因子：
0
作者：
Daniero, James J;Ekbom, Dale C;Gelbard, Alexander;Akst, Lee M;Hillel, Alexander T
通讯作者：
Hillel, Alexander T

Evaluation of Dyspnea Outcomes After Endoscopic Airway Surgery for Laryngotracheal Stenosis.

喉气管狭窄内镜气道手术后呼吸困难结果的评估。

DOI：
发表时间：
2016-11-01
期刊：
影响因子：
0
作者：
Samad, Idris;Akst, Lee;Karatayli;Teets, Kristine;Simpson, Marissa;Sharma, Ashwyn;Best, Simon R A;Hillel, Alexander T
通讯作者：
Hillel, Alexander T

Factors Affecting Dilation Interval in Patients With Granulomatosis With Polyangiitis-Associated Subglottic and Glottic Stenosis.

影响肉芽肿病伴多血管炎相关声门下和声门狭窄患者扩张间隔的因素。

DOI：
发表时间：
2021-12
期刊：
影响因子：
0
作者：
Chen, Lena W;Lina, Ioan;Motz, Kevin;Berges, Alexandra J;Ospino, Rafael;Seo, Philip;Hillel, Alexander T
通讯作者：
Hillel, Alexander T

Voice Outcomes in Laryngotracheal Stenosis: Impact of the Montgomery T-tube.

喉气管狭窄的声音结果：蒙哥马利 T 形管的影响。