The impact of the HIV reservoir on pulmonary myeloid cells: virology, phenotype, and function

HIV 储存库对肺髓细胞的影响：病毒学、表型和功能

基本信息

批准号：
10542361
负责人：
Joshua Vasquez
金额：
$ 19.12万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-08 至 2023-09-11
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10542361
关键词：
Address Affect Age Alveolar Alveolar Macrophages Antibodies Area Award Bioinformatics Biological Assay Biometry Blood capillaries CD14 gene CD4 Positive T Lymphocytes CD80 gene CD86 gene California Cell Count Cells Cellular biology Chronic Chronic Obstructive Pulmonary Disease Clinical Communicable Diseases Computer Analysis Consequences of HIV Coupled Critical Care Cytometry DNA Data Defect Development Disease Disease Progression Enrollment Environment FCGR3B gene Fellowship Frequencies Functional disorder General Hospitals General Population Goals HIV HIV Infections Human IL18 gene Immune System Diseases Immunologic Techniques Immunologist Immunology In Situ Hybridization Individual Inflammasome Inflammation Inhalation Innate Immune System Interleukin-1 beta International Investigation Laboratories Liquid substance Lung Lung diseases Measures Mediating Medicine Mentored Research Scientist Development Award Mentors Mentorship Methods Myeloid Cells Nucleic Acids Organ PTPNS1 gene Participant Pathogenesis Pathology Patients Persons Phagocytosis Phenotype Pneumonia Productivity Pulmonary Inflammation Pulmonology RNA Records Research Risk Sampling San Francisco Scientist Seminal Signal Pathway Specialist Standardization T-Lymphocyte Time Tissues Tobacco smoke Toxin Training Transforming Growth Factor beta Translational Research Universities Vaccines Viral Virus Replication Work antiretroviral therapy body system career clinical training comorbidity cytokine high dimensionality immunomodulatory therapies novel novel therapeutics professor programs receptor skills systemic inflammatory response targeted treatment therapeutic development translational immunology translational scientist virology

项目摘要

PROJECT SUMMARY/ABSTRACT This is an application for a K01 award for Dr. Joshua Vásquez, MD, Assistant Professor in the Division of Experimental Medicine and the Division Pulmonary and Critical Care Medicine at the University of California at San Francisco who is establishing himself as a clinician-scientist in HIV immunology. His goal is to apply his pulmonary medicine background from a clinical fellowship to study the mechanisms that underlie pulmonary inflammation and immune dysfunction in treated HIV disease. This award will provide him with the support to accomplish the following goals: (1) to characterize the pulmonary reservoir of HIV and (2) to determine whether phenotypic and functional defects persist in alveolar macrophages responsible for patrolling the alveolar- capillary barrier, despite antiretroviral therapy, particularly among those with low CD4+ T cell nadirs. To achieve these goals, he will have four co-mentors who each have unique strengths and established track records of productive scientific investigation and mentorship of research fellows. His primary mentor is Dr. Peter Hunt, the interim chief of the Division of Experimental Medicine at UCSF/Zuckerberg San Francisco General Hospital, and an internationally-recognized expert in HIV translational immunology, specifically the mechanisms and consequences of chronic inflammation during treated HIV disease. Dr. Vasquez will also work with co-mentors Dr. Joseph (Mike) McCune, a preeminent immunologist who has conducted many seminal studies in HIV pathogenesis; Dr. Clifford Lowell, Chair of Laboratory Medicine and a recognized expert on intracellular signaling pathways regulating inflammation in the innate immune system; and Dr. Laurence Huang, an internationally-recognized expert in the pulmonary complications of HIV disease. He has also engaged active collaborators who will continue to provide focused support in the areas of: HIV tissue reservoir assessment by PCR (Dr. Steven Yukl), HIV-associated tissue pathology (Dr. Zoltan Laszik), alveolar macrophage immunology (Dr. Mehrdad Arjomandi), biostatistics (Dr. Peter Bacchetti), pulmonary immunology (Dr. Prescott Woodruff), as well as mass cytometry and high dimensional computational analysis (Dr. Matthew Spitzer). As a part of this award, he will pursue additional training in translational research, immunology methods, and bioinformatics. Leveraging access to unique patient samples, he will apply existing and novel immunologic techniques to determine how alveolar macrophage programs are altered in the setting of HIV disease. The results of these studies should be widely applicable to our understanding of the tissue immunology of other common diseases and be useful to guide the development of immunomodulatory therapies targeted at myeloid cells. Ultimately, the training and research plans outlined here will support his transition from being a basic immunologist and clinical pulmonary/critical care specialist to being a translational researcher equipped with the skills to pursue an independent career focused on elucidating the fundamental principles of myeloid cell biology and informing the development of therapeutics and vaccines for infectious diseases.

项目摘要/摘要这是医学博士JoshuaVásquez博士的K01奖的申请。加利福尼亚大学的实验医学以及分区的肺和重症监护医学旧金山正在确立自己是艾滋病毒免疫学方面的临床科学家。他的目标是应用他的从临床研究金的肺部医学背景，研究肺部基础的机制治疗的HIV疾病中的炎症和免疫功能障碍。该奖项将为他提供支持实现以下目标：（1）表征艾滋病毒的肺部储层和（2）确定是否是否表型和功能缺陷持续存在于负责巡逻肺泡的肺泡巨噬细胞中毛细血管屏障，毒性抗逆转录病毒疗法，尤其是在CD4+ T细胞低下的患者中。实现这些目标，他将有四个拥有独特优势的副官员，并确定了研究研究员的生产科学研究和心态。他的主要心态是彼得·亨特博士 UCSF/Zuckerberg San Francisco总医院实验医学部临时主任以及国际公认的HIV转化免疫学专家，特别是机制和治疗的HIV疾病期间慢性炎症的后果。 Vasquez博士还将与联合官员合作杰出的免疫学家约瑟夫（Mike）McCune博士已经进行了许多艾滋病毒研究发病;实验室医学主席，知名专家Clifford Lowell博士信号通路调节先天免疫系统中的炎症；还有劳伦斯·黄博士国际认可的HIV疾病肺并发症专家。他还活跃了合作者将继续在以下领域提供以下方面的专注支持：艾滋病毒组织库评估 PCR（Steven Yukl博士），与HIV相关的组织病理学（Zoltan Laszik博士），肺泡巨噬细胞免疫学（Mehrdad Arjomandi博士），生物统计学（Peter Bacchetti博士），肺免疫学（Prescott Woodruff博士），以及质量细胞术和高维计算分析（Matthew Spitzer博士）。作为其中的一部分奖项，他将在翻译研究，免疫学方法和生物信息学方面接受其他培训。利用获取独特的患者样本的访问，他将应用现有和新颖的免疫学技术确定在HIV疾病的情况下如何改变肺泡巨噬细胞计划。这些结果研究应广泛适用于我们对其他常见疾病的组织免疫学的理解并有助于指导针对髓样细胞的免疫调节疗法的发展。最终，这里概述的培训和研究计划将支持他从基本免疫学家和临床肺/重症监护专家，是一名具有购买技能的翻译研究人员独立职业，重点是阐明髓样细胞生物学的基本原理并告知传染病的理论和疫苗的发展。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Lower PDL1, PDL2, and AXL Expression on Lung Myeloid Cells Suggests Inflammatory Bias in Smoking and Chronic Obstructive Pulmonary Disease.

肺骨髓细胞上较低的 PDL1、PDL2 和 AXL 表达表明吸烟和慢性阻塞性肺疾病中存在炎症偏向。

DOI：
10.1165/rcmb.2020-0085oc
发表时间：
2020
期刊：
American journal of respiratory cell and molecular biology
影响因子：
6.4
作者：
Vasudevan,Sreelakshmi;Vásquez,JoshuaJ;Chen,Wenxuan;Aguilar-Rodriguez,Brandon;Niemi,EreneC;Zeng,Siyang;Tamaki,Whitney;Nakamura,MaryC;Arjomandi,Mehrdad
通讯作者：
Arjomandi,Mehrdad

Novel In Situ Hybridization and Multiplex Immunofluorescence Technology Combined With Whole-slide Digital Image Analysis in Kidney Transplantation

肾移植中新型原位杂交和多重免疫荧光技术与全玻片数字图像分析相结合