Elucidating the Genomic Determinants of Outcomes in Idiopathic Pulmonary Fibrosis
Elucidating the Genomic Determinants of Outcomes in Idiopathic Pulmonary Fibrosis
批准号:
10670456
负责人:
Justin M Oldham
金额:
$10.35万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-09-01 至 2023-02-28
中文摘要
项目总结/文摘
英文摘要
PROJECT SUMMARY/ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a rare, but devastating interstitial lung disease characterized by a
progressive decline in lung function and a median survival of 3-5 years after diagnosis. Despite the poor
prognosis, IPF follows a highly variable clinical course, whereby most patients experience gradual disease
progression, some demonstrate relative stability and a small group dies from rapidly progressive disease. Anti-
fibrotic therapies were recently approved for the treatment of IPF, but it remains unclear which IPF phenotypes
derive the most benefit. Recent advances in genomic technology provide an excellent opportunity to improve
our understanding of IPF progression and treatment response. In this proposal, I aim to take advantage of
these genomic advances to identify single nucleotide polymorphisms (SNPs) linked to relevant IPF outcomes. I
will do this using DNA samples collected from patients enrolled in past and current IPF clinical trials, along with
two large IPF registries. My central hypothesis is that patients genetically predisposed to death, disease
progression and treatment response can be prospectively identified using SNPs linked to these endpoints. I will
first conduct a genome-wide survival analysis to identify SNPs linked to early IPF mortality. I will then genotype
relevant susceptibility and outcome-associated SNPs in several clinical trial datasets to determine whether
they predict relevant trial endpoints, including pulmonary function decline and hospitalization. Finally, I will
genotype SNPs at potential pharmacogenetic loci to determine whether such SNPs modulate the response to
anti-fibrotic therapy. This work will advance my long-term career goal of incorporating genetics into clinical
decision-making in patients with IPF. Concurrently I will pursue a career development plan that will provide
outstanding mentorship, hands-on laboratory experience and additional training in genetic epidemiology,
statistical genetics, and bioinformatics. This K23 award is vital to successful completion of this proposal and
timely execution of my career development plan, as it will provide the time necessary to meet the realistic
milestones that have set in conjunction with my advisory committee. Ultimately this award will allow me to
successfully compete for R01 funding aimed at advancing my long-term goal above.
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Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis.
人类白细胞抗原(HLA)变异与特发性肺纤维化的关联研究。
DOI:
10.1101/2023.07.20.23292940
发表时间:
2023
期刊:
the preprint server for health sciences
影响因子:
--
作者:
[Guillen-Guio B]
通讯作者:
Guillen-Guio B
Weighing on Our Minds: Baseline BMI and Weight Loss as Predictors of Interstitial Lung Disease Outcome.
掂量我们的心:基线 BMI 和体重减轻作为间质性肺疾病结果的预测因子。
DOI:
10.1016/j.chest.2021.11.013
发表时间:
2022
期刊:
Chest
影响因子:
9.6
作者:
[Pugashetti,JanelleVu, Oldham,JustinM]
通讯作者:
Oldham,JustinM
Rebuttal From Drs Oldham and Danoff.
奥尔德姆博士和丹诺夫博士的反驳。
DOI:
10.1016/j.chest.2018.08.1071
发表时间:
2019
期刊:
Chest
影响因子:
9.6
作者:
[Oldham,JustinM, Danoff,SonyeK]
通讯作者:
Danoff,SonyeK
Clinical Genetics in Interstitial Lung Disease.
间质性肺病的临床遗传学。
DOI:
10.3389/fmed.2018.00116
发表时间:
2018
期刊:
Frontiers in medicine
影响因子:
3.9
作者:
[Newton,ChadA, Molyneaux,PhilipL, Oldham,JustinM]
通讯作者:
Oldham,JustinM
DOI:
10.1016/j.chest.2021.06.035
发表时间:
2022-02
期刊:
CHEST
影响因子:
9.6
作者:
[Hunninghake, Gary M., Goldin, Jonathan G., Kadoch, Michael A., Kropski, Jonathan A., Rosas, Ivan O., Wells, Athol U., Yadav, Ruchi, Lazarus, Howard M., Abtin, Fereidoun G., Corte, Tamera J., de Andrade, Joao A., Johannson, Kerri A., Kolb, Martin R., Lynch, David A., Oldham, Justin M., Spagnolo, Paolo, Strek, Mary E., Tomassetti, Sara, Washko, George R., White, Eric S.]
通讯作者:
White, Eric S.
共 16 条
Proteomic Profiling of Idiopathic Pulmonary Fibrosis Progression Trajectory
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批准号:10708256
-
项目类别:
-
资助金额:$71.65万
-
财政年份:2023
-
负责人:Justin M Oldham
-
依托单位:
Derivation and validation of a clinical-molecular signature to predict fibrotic progression and treatment response in patients with autoimmune interstitial lung disease
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批准号:10275747
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项目类别:
-
资助金额:$39.97万
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财政年份:2021
-
负责人:Justin M Oldham
-
依托单位:
Interrogation of the inflammasome to identify biomarkers of progressive interstitial lung disease
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批准号:10375577
-
项目类别:
-
资助金额:$7.85万
-
财政年份:2021
-
负责人:Justin M Oldham
-
依托单位:
Interrogation of the inflammasome to identify biomarkers of progressive interstitial lung disease
-
批准号:10213535
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项目类别:
-
资助金额:$7.85万
-
财政年份:2021
-
负责人:Justin M Oldham
-
依托单位:
Elucidating the genomic determinants of outcomes in idiopathic pulmonary fibrosis
-
批准号:9980986
-
项目类别:
-
资助金额:$18.27万
-
财政年份:2017
-
负责人:Justin M Oldham
-
依托单位:
Elucidating the genomic determinants of outcomes in idiopathic pulmonary fibrosis
-
批准号:9369287
-
项目类别:
-
资助金额:$18.27万
-
财政年份:2017
-
负责人:Justin M Oldham
-
依托单位:
Elucidating the genomic determinants of outcomes in idiopathic pulmonary fibrosis
-
批准号:9764465
-
项目类别:
-
资助金额:$18.27万
-
财政年份:2017
-
负责人:Justin M Oldham
-
依托单位:
Elucidating the genomic determinants of outcomes in idiopathic pulmonary fibrosis
-
批准号:10238126
-
项目类别:
-
资助金额:$7.92万
-
财政年份:2017
-
负责人:Justin M Oldham
-
依托单位:
海外基金