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Genomic Signatures for Idiopathic Interstitial Pneumonia

特发性间质性肺炎的基因组特征

基本信息

批准号：
8119711
负责人：
David Albert Schwartz
金额：
$ 80.55万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-24 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8119711
关键词：
Acute Acute interstitial pneumonia Address Biological Biopsy Biopsy Specimen Categories Characteristics Chromosomes, Human, Pair 10 Chronic Classification Clinical Complex Copy Number Polymorphism Development Diagnosis Diagnostic Diagnostic radiologic examination Disease Early Diagnosis Family Fibrosis Formalin Freezing Future Gene Expression Gene Expression Profile Genes Genetic Genetic Transcription Genetic Variation Genome Genomics Goals Hamman-Rich syndrome Immunohistochemistry Individual Indolent Interstitial Pneumonia Label Lead Lung Lymphocyte Maps Measures Medical Research Molds Molecular Molecular Profiling Mutation National Heart, Lung, and Blood Institute Nonspecific Interstitial Pneumonia Outcome Pathology Patients Pattern Phase Phenotype Physiology Play Pneumonia Population Population Control Population Study Pulmonary Surfactant-Associated Protein C Quantitative Trait Loci RNA Recording of previous events Research Respiratory Failure Role Sampling Single Nucleotide Polymorphism Single Nucleotide Polymorphism Map Structure of parenchyma of lung Telomerase Testing Therapeutic Tissue Microarray Transcript Validation Weight abstracting clinical phenotype experience follower of religion Jewish genetic variant genome-wide innovation interest member molecular phenotype novel patient population response

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this project is to combine genetic and genomic findings in patients with idiopathic interstitial pneumonia (IIP) to develop and validate phenotypically anchored molecular signatures that serve to refine the diagnostic criteria for this group of complex diseases. IIP has traditionally been defined by objective clinical characteristics (history, physiology, radiography, and pathology). This approach splits out diseases that appear to be homogeneous including acute interstitial pneumonia (AIP), lymphocytic pneumonia (LIP), and cryptogenic organizing pneumonia (COP) but idiopathic pulmonary fibrosis (IPF), non specific interstitial pneumonia (NSIP), and a group of IIPs that do not fit a specific category remain heterogeneous in terms of overlapping patterns that often defies diagnostic labeling. Substantial evidence supports the concept that these latter categories of IIP, as currently defined, still comprise a heterogeneous phenotype in terms of pattern of presentation, outcome, and response to therapy. It is also possible that even those entities that appear to be homogeneous may in fact comprise mixed groups. For example, what appears clinically to be AIP may, in fact, represent an acute exacerbation of IPF that has hitherto experienced a very indolent and therefore clinically unrecognized course that has developed a rapid explosive phase. While the biological features of IIP are emerging, these molecular attributes (or signatures) that are prototypical of IIP have not yet been integrated with the traditional clinical diagnostic characteristics for these fibrosing interstitial pneumonias. In IIP, gene expression studies from our lab and others have demonstrated unique molecular signatures for some (IPF and familial forms of IIP) but not all (NSIP) forms of this disease. Given the overlapping classification of IIP subtypes and the likelihood that multiple genes play a role in the development of this group of diseases, this is not at all surprising. For instance, about 10% of patients with IIP develop disease due to mutations in either surfactant protein C or telomerase genes, presumably resulting in two distinct molecular signatures. We have recently performed a linkage study in 82 families with = 2 members with probable/definite IIP and have identified regions on chromosomes 10, 11, and 12 that likely contain genes contributing to familial forms of IIP, again presumably resulting in distinct molecular signatures. The compelling challenge is to combine genetic and genomic approaches in patients with IIP to define molecular phenotypes of IIP that can be used to distinguish the clinical aspects of this group of complex diseases. To address this challenge, we hypothesize that the IIP transcriptome is influenced by genetic variants and that, in combination with clinical characteristics, these molecular signatures can be used to refine the diagnostic criteria for this group of complex diseases. To test this hypothesis, we will combine the results of genome-wide RNA expression with regions/genes of interest from genetic studies to develop and validate phenotypically anchored molecular signatures for IIP and its subtypes. (End of Abstract)

描述（由申请人提供）：

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

Role of macrophage receptor with collagenous structure in innate immune tolerance.

DOI：
10.4049/jimmunol.1202942
发表时间：
2013-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Jing J;Yang IV;Hui L;Patel JA;Evans CM;Prikeris R;Kobzik L;O'Connor BP;Schwartz DA
通讯作者：
Schwartz DA

Epigenetics of idiopathic pulmonary fibrosis.

特发性肺纤维化的表观遗传学。

DOI：
10.1016/j.trsl.2014.03.011
发表时间：
2015-01
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
0
作者：
Yang IV;Schwartz DA
通讯作者：
Schwartz DA

The peripheral blood transcriptome identifies the presence and extent of disease in idiopathic pulmonary fibrosis.

DOI：
10.1371/journal.pone.0037708
发表时间：
2012
期刊：
PloS one
影响因子：
3.7
作者：
Yang IV;Luna LG;Cotter J;Talbert J;Leach SM;Kidd R;Turner J;Kummer N;Kervitsky D;Brown KK;Boon K;Schwarz MI;Schwartz DA;Steele MP
通讯作者：
Steele MP

Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis.

DOI：
10.1136/thoraxjnl-2012-202943
发表时间：
2013-12
期刊：
Thorax
影响因子：
10
作者：
Yang IV;Coldren CD;Leach SM;Seibold MA;Murphy E;Lin J;Rosen R;Neidermyer AJ;McKean DF;Groshong SD;Cool C;Cosgrove GP;Lynch DA;Brown KK;Schwarz MI;Fingerlin TE;Schwartz DA
通讯作者：
Schwartz DA

The next generation of complex lung genetic studies.

下一代复杂的肺部遗传学研究。