This Proteome & Genome Core (PPG Core B) will provide essential, cutting edge, proteomic/transcriptomic/genetic expertise to facilitate the translational impact of this highly integrated PPG. This PPG Core will be responsible for providing the research investigators with a well characterized ARDS biobank (i.e. DNA from European descent and African descent subjects), a complete list of tagging single nucleotide polymorphisms (tSNPs) for each PPG candidate gene, mid-throughput genotyping services, and data analysis tools to test for association between PPG-studied SNPs and susceptibility and severity of ARDS. The functional non-synonymous coding SNPs will be screened in silico to identify their impact on protein structure and function (protein-protein interaction, catalytic activity, post-translational modification) by computational protein structure molecular modeling, with protein-protein interaction validated by surface plasmon resonance (SPR) screening. Effects of exon-intron boundary SNPs on alternative splicing of these key genes will be analyzed by in silico prediction and further validated by SNP-containing minigene constructs in individual projects. PPG Core B will provide the service to generate the mutated DNA constructs (with disease-associated SNP) to generate recombinant protein used in SPR, or GRF-labeled protein for cellular location tracking in endothelial cells (to be used in Core D and individual projects). In addition, this PPG Core will further validate the genomic expression data by proteomic approaches (2-D protein gel and mass spectrometry). On top of the protein level characterization, the PPG Core B will define the protein translational modification (PTM) status including phosphorylation, nitration, and ubiquitination via traditional mass spectrometry analysis. PPG Core B will utilize the up-to-date technologies to provide a proteomic-genomic study platform for all three Projects and generate novel information on the genes targeted for investigation in this PPG. This PPG Core will also provide software and hardware infrastructure for (i) federated tissue management (e.g. chain of custody while transferring tissues from any lab to any Core) and (ii) secure data exchange between Cores and Research investigators. Core B will also resource investigators and Cores with TissueMetrix tissue management software that also provides chain of custody management of samples transferred between investigators and Cores and reconciliation between lists of samples send and received. In addition, large files generated by the cores will be transferred to investigators using a secure IPSwitch portal that also manages authentication and keeps logs of accessed files by legitimate users (e.g. genomics, transcriptomic, proteomics, imaging).

Public Health Relevance

Each of the PPG projects focuses on a specific cytoskeletal target, but they all share similar regulation via genetic and post-translational modification. Core B will serve as a centralized infrastructure for providing expertise in the genomic and proteomic analysis of target DNA, RNA, and protein regulation.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-PPG-A)
Program Officer
Reineck, Lora A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Arizona
Domestic Higher Education
United States
Zip Code
Bime, Christian; Pouladi, Nima; Sammani, Saad et al. (2018) Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor. Am J Respir Crit Care Med 197:1421-1432
Gross, Christine M; Kellner, Manuela; Wang, Ting et al. (2018) LPS-induced Acute Lung Injury Involves NF-?B-mediated Downregulation of SOX18. Am J Respir Cell Mol Biol 58:614-624
Liu, Pengfei; Rojo de la Vega, Montserrat; Sammani, Saad et al. (2018) RPA1 binding to NRF2 switches ARE-dependent transcriptional activation to ARE-NRE-dependent repression. Proc Natl Acad Sci U S A 115:E10352-E10361
Wang, X; Wang, L; Garcia, J G N et al. (2018) The Significant Role of c-Abl Kinase in Barrier Altering Agonists-mediated Cytoskeletal Biomechanics. Sci Rep 8:1002
Mascarenhas, Joseph B; Tchourbanov, Alex Y; Danilov, Sergei M et al. (2018) The Splicing Factor hnRNPA1 Regulates Alternate Splicing of the MYLK Gene. Am J Respir Cell Mol Biol 58:604-613
Oita, Radu C; Camp, Sara M; Ma, Wenli et al. (2018) Novel Mechanism for Nicotinamide Phosphoribosyltransferase Inhibition of TNF-?-mediated Apoptosis in Human Lung Endothelial Cells. Am J Respir Cell Mol Biol 59:36-44
Brown, Robert V; Wang, Ting; Chappeta, Venkateshwar Reddy et al. (2017) The Consequences of Overlapping G-Quadruplexes and i-Motifs in the Platelet-Derived Growth Factor Receptor ? Core Promoter Nuclease Hypersensitive Element Can Explain the Unexpected Effects of Mutations and Provide Opportunities for Selective Targeting of J Am Chem Soc 139:7456-7475
Szilágyi, Keely L; Liu, Cong; Zhang, Xu et al. (2017) Epigenetic contribution of the myosin light chain kinase gene to the risk for acute respiratory distress syndrome. Transl Res 180:12-21
Wang, X; Bleher, R; Wang, L et al. (2017) Imatinib Alters Agonists-mediated Cytoskeletal Biomechanics in Lung Endothelium. Sci Rep 7:14152
Mascarenhas, Joseph B; Tchourbanov, Alex Y; Fan, Hanli et al. (2017) Mechanical Stress and Single Nucleotide Variants Regulate Alternative Splicing of the MYLK Gene. Am J Respir Cell Mol Biol 56:29-37

Showing the most recent 10 out of 18 publications