Immunoengineering

免疫工程

基本信息

批准号：
10702979
负责人：
Kaitlyn Sadtler
金额：
$ 64.14万
依托单位：
NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10702979
关键词：
2019-nCoV Adipocytes Admission activity Africa Age Antibodies Antibody Formation Award Biocompatible Materials Biological Markers Biomaterials Research Biomedical Engineering C57BL/6 Mouse COVID-19 vaccination Calendar Cells Cicatrix Clinical Color Communities Data Databases Dendritic Cells Drug usage Ear Evaluation Fatty acid glycerol esters Fibrosis Flow Cytometry Foreign Bodies General Population Genetic Growth High Prevalence Histologic Hospitalization Human Immune Immune response Immunity Immunocompromised Host Immunologics In Vitro Individual Injury MRL/MpJ Mouse Manuscripts Modeling Muscle National Institute of Biomedical Imaging and Bioengineering Natural regeneration Organ Patients Population Prevalence Publications Publishing Rare Diseases Rattus Research Personnel Resource Sharing Role Scientist Seroprevalences Services Southeastern Asia T-Cell Activation Testing Time Tissues Trauma United States United States National Institutes of Health Up-Regulation Vaccination Work breakthrough infection healing immune function immune self tolerance immunoengineering implantable device implantation interest lipid biosynthesis mouse model physical science programs recruit regenerative response seropositive tissue regeneration transcriptome sequencing

项目摘要

Analysis of SARS-CoV-2 Seroprevalence in the US Population and Rare Disease Patients Previously we established a range of antibody tests to evaluate SARS-CoV-2 seroprevalence (JoCI, 2021, Nat Comms 2021, JID 2021) in the US population (STM 2021, medRxiv) and abroad including Africa and Southeast Asia (CID 2022, JID 2021, EID 2022). We are continuing to study US seroprevalence over the course of a year from 2020 to 2021 and are finalizing the analysis of that study, which includes data on undiagnosed reinfections and undiagnosed vaccination breakthrough infections. We are also looking at seroprevalence in a population of rare disease patients during the same timeframe. We expect both of these studies to be submitted for publication by the end of this calendar year. Antibody production from SARS-CoV-2 vaccination in immunodeficient patients We have adapted our SARS-CoV-2 seroassays for evaluation of immune response to vaccination in immunocompromised/immunodeficient patients. Through this we have also transitioned our seroassays to the Bioengineering and Physical Sciences shared resource (BEPS) wherein any NIH scientist can request these to be completed in a for-service manner. We expect the first publication of this study to be submitted by the end of the calendar year. SARS-CoV-2 in trauma admits and correlation with drug use As our lab is interested in the immunologic responses to trauma and downstream effects on tissue growth and regeneration, we evaluated the intersection with SARS-CoV-2 through a seroprevalence evaluation. In this study we were able to show that trauma admits had a higher prevalence of SARS-CoV-2 in comparison to the general population. We also saw a correlation with drug usage, wherein individuals on depressants were less likely to be seropositive for SARS-CoV-2. We have preprinted this study and expect to submit this for publication by the end of 2022. Immunologic self-tolerance in trauma and biomaterial implantation As we finalize our work on SARS-CoV-2 we began our biomaterials research in earnest, and have preprinted our first biomaterials work wherein we describe a dendritic cell subset that appears to be critical in regulating the immune response to trauma. We showed both a putative mechanism of their recruitment, as well as the role of these cells in controlling T cell activation and minimizing further tissue damage after the initial trauma. Interactions between white fat and immunity after injury in a super healing mouse model The MRL/MpJ mouse is famous for being able to fully heal an ear punch in comparison to the C57BL/6 mouse which scars. We wanted to investigate the difference in immune responses to pro-regenerative versus pro-fibrotic materials in the MRL versus B6 models. We found a strong upregulation of adipogenesis in the MRL model with large, disperse numbers of white fat cells noted histologically, and white fat genetic programs upregulated as determined by RNAseq. We are currently evaluating the immunologic differences and hope to have this manuscript submitted by November 2022. Immune responses to trauma in a rat model In order to expand our findings to different species, we developed a flow cytometry panel to evaluate immune responses to muscle trauma in a rat model. We developed the largest flow cytometry panel currently published and used it to characterize immune cells in a muscle injury model in a rat. This manuscript was published in Cells, Tissues, and Organs in the Young Investigators Award issue. Adusei et al. CTO. Systemic responses to trauma in human patients at hospital admission As we expanded our analyses of immune responses to trauma in different species, we continued to develop our evaluation of human immune response to trauma. We evaluated systemic immune profile of trauma admits at the time of admission and we found several correlations with age, and are currently assembling a full database of biomarker data alongside clinical information of 1500 patients which we will be analyzing in the coming weeks.

分析美国人群中的SARS-COV-2血清阳性率和罕见病患者以前，我们建立了一系列抗体测试，以评估美国人口中的SARS-COV-2血清阳性率（Joci，2021，Nat Comms 2021，JID 2021）（STM 2021，MEDRXIV）和国外，包括非洲和东南亚，包括非洲和东南亚（CID 2022，JID 2021，EID 2021，EID 2022）。从2020年到2021年的一年中，我们将继续研究我们的血清阳性，并最终确定了该研究的分析，其中包括有关未诊断的重新感染和未诊断疫苗接种突破感染的数据。我们还在同一时间范围内研究罕见病患者人群的血清阳性。我们希望这两项研究都将在本日历年结束时提交出版。免疫缺陷患者中SARS-COV-2疫苗接种的抗体产生我们已经适应了SARS-COV-2血清测量，以评估免疫功能低下/免疫缺陷患者对疫苗接种的免疫反应。通过此，我们还将血清测定过渡到了生物工程和物理科学共享资源（BEP），其中任何NIH科学家都可以要求以服务方式完成。我们预计将在日历年结束时提交这项研究的首次出版物。 SARS-COV-2在创伤中接受并与吸毒相关由于我们的实验室对创伤和下游对组织生长和再生的影响感兴趣，因此我们通过血清阳性评估评估了与SARS-COV-2的相交。在这项研究中，我们能够表明，与普通人群相比，创伤承认SARS-COV-2的患病率更高。我们还看到了与药物使用的相关性，其中抑郁剂对SARS-COV-2的血清阳性可能性较小。我们已经预先刷新了这项研究，并希望在2022年底之前提交该研究以供出版。创伤和生物材料植入的免疫学自我耐受性当我们最终确定SARS-COV-2的工作时，我们认真地开始了生物材料研究，并预先刷新了我们的第一批生物材料工作，其中我们描述了一个树突状细胞子集，这对于调节对创伤的免疫反应至关重要。我们既展示了它们募集的推定机制，也显示了这些细胞在控制T细胞激活和最小化最初创伤后进一步的组织损伤中的作用。在超级愈合小鼠模型中受伤后的白脂肪与免疫力之间的相互作用 MRL/MPJ鼠标与C57BL/6鼠标相比，以能够完全治愈耳孔而闻名。我们想研究MRL与B6模型中对促再生性材料与促纤维化材料的免疫反应差异。我们发现，在MRL模型中，脂肪形成的强烈上调在组织学上注意到大量的白色脂肪细胞数量，而白脂肪遗传程序则在RNASEQ确定的上调上调。我们目前正在评估免疫学差异，并希望在2022年11月之前提交此手稿。大鼠模型中对创伤的免疫反应为了将我们的发现扩展到不同物种，我们开发了一个流式细胞仪面板，以评估大鼠模型中对肌肉创伤的免疫反应。我们开发了当前发表的最大流式细胞仪面板，并将其用来表征大鼠肌肉损伤模型中的免疫细胞。该手稿在“年轻研究者奖”问题中发表在细胞，组织和器官中。 Adusei等。 CTO。住院时人类患者的创伤的全身反应随着我们扩大了对不同物种中创伤的免疫反应的分析，我们继续对人类免疫反应的评估进行评估。我们在入院时评估了允许的创伤的全身免疫特征，并发现了与年龄的几个相关性，目前正在组装一个完整的生物标志物数据数据库以及1500名患者的临床信息，我们将在未来几周内进行分析。