The goal of this integrative program project grant, ?Systems Biology of Airway Disease?, is to identify the shared genetic, genomic and epigenetic features between asthma and COPD, two of the most common chronic lung diseases.
Aimi ng to translate human genetics and genomics to biology and eventually benefit disease treatment, this PPG differs from other systems biology proposals because of its comprehensive functional assessment pipelines, which include a series of functional validations on genetic variants, candidate genes and network modules shared between asthma and COPD. Such functional validation will greatly speed up and prioritize candidate disease genes as therapeutic targets. Core C will provide overall functional support to all projects in this PPG. The function of Core C includes: (1) identifying functional GWAS and sequencing variants that are associated with airflow obstruction in both asthma and COPD (Project 1); (2) experimentally validating disease modules built upon genetics, genomics and epigenetics from asthma and COPD subjects (Projects 1,2 and 3); (3) establishing a cellular phenotypic screening model that is relevant to asthma and COPD and applying loss-of-function approach by RNAi in this model to assess novel disease genes (Project 2 and 3); (4) modeling cigarette smoke induced DNA methylome changes in primary human bronchial epithelial cells (Project 3). We will provide needed biological consulting and support to all projects. To fulfill these functions of Core C and, thus, ensure successful completion of this PPG, Core C is assembled with three senior research assistants directed by the experienced cell biologist, Dr. Anny Xiaobo Zhou, the Director of Functional Genomics Laboratory who will be assisted by Dr. Mark Perrella, a senior molecular biologist and pulmonologist in the Division of Pulmonary and Critical Care Medicine at Brigham and Women's Hospital, and a longtime collaborator of Dr. Zhou and several other key investigators of the PPG. Core C is based on a well- equipped molecular and cell biology laboratory that has access to all needed resources. In addition, Dr. Zhou has been a longtime collaborator of all Project Principal Investigators, Drs. Scott Weiss, Benjamin Raby and Dawn DeMeo. They have a demonstrated successful track record and productivity that will ensure Core C will meet the overall functional needs of this PPG.

Public Health Relevance

This program project aims to identify shared mechanism between asthma and COPD. To achieve this goal, a functional genomics core is needed to ensure the successful completion of functional assessments on genetic variants, novel disease genes, epigenetics and shared disease modules by experimental biology approaches.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
1P01HL132825-01
Application #
9150875
Study Section
Special Emphasis Panel (HLBP (JH))
Program Officer
Gan, Weiniu
Project Start
Project End
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$464,970
Indirect Cost
$203,015
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Dehmamy, Nima; Milanlouei, Soodabeh; Barabási, Albert-László (2018) A structural transition in physical networks. Nature 563:676-680
Santolini, Marc; Barabási, Albert-László (2018) Predicting perturbation patterns from the topology of biological networks. Proc Natl Acad Sci U S A 115:E6375-E6383
Zhou, Xuezhong; Lei, Lei; Liu, Jun et al. (2018) A Systems Approach to Refine Disease Taxonomy by Integrating Phenotypic and Molecular Networks. EBioMedicine 31:79-91
Hecker, Julian; Xu, Xin; Townes, F William et al. (2018) Family-based tests for associating haplotypes with general phenotype data: Improving the FBAT-haplotype algorithm. Genet Epidemiol 42:123-126
Yun, Jeong H; Lamb, Andrew; Chase, Robert et al. (2018) Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol 141:2037-2047.e10
Peng, Cheng; Cardenas, Andres; Rifas-Shiman, Sheryl L et al. (2018) Epigenome-wide association study of total serum immunoglobulin E in children: a life course approach. Clin Epigenetics 10:55
Morrow, Jarrett D; Cho, Michael H; Platig, John et al. (2018) Ensemble genomic analysis in human lung tissue identifies novel genes for chronic obstructive pulmonary disease. Hum Genomics 12:1
Li, Xuan; Fu, Yuejiao; Wang, Xiaogang et al. (2018) Detecting Differentially Variable MicroRNAs via Model-Based Clustering. Int J Genomics 2018:6591634
Hecker, Julian; Prokopenko, Dmitry; Lange, Christoph et al. (2018) PolyGEE: a generalized estimating equation approach to the efficient and robust estimation of polygenic effects in large-scale association studies. Biostatistics 19:295-306
Lopes-Ramos, Camila M; Kuijjer, Marieke L; Ogino, Shuji et al. (2018) Gene Regulatory Network Analysis Identifies Sex-Linked Differences in Colon Cancer Drug Metabolism. Cancer Res 78:5538-5547

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