In current drug development, there exist huge gaps in translating activity in the preclinical screening models into desirable clinical outcomes in humans. In this project titled "Rapid reverse translational drug repositioning: novel computational approaches, unique data, and broad implications," we propose to develop a novel drug discovery strategy that directly translates observed phenotypic perturbations caused by drugs or diseases in human bodies into novel disease treatments in humans (direct human ->human translation), and retrospectively corroborates novel drug indications using large amounts of patient electronic health record (EHR) data. In this way, we can minimize the translational gap between pre-clinical testing results in animal models and clinical outcomes in humans in current drug development.

Public Health Relevance

In this project titled Rapid reverse translational drug repositioning: novel computational approaches, unique data, and broad implications, we propose to develop a novel drug discovery strategy that directly translates observed phenotypic perturbations caused by drugs or diseases in human bodies into novel disease treatments in humans (direct human ->human translation). In this way, we can minimize the translational gap between pre-clinical testing results in animal models and clinical outcomes in humans, which is a significant problem in current drug development.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2HD084068-01
Application #
8757089
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (56))
Program Officer
Tsilou, Katerina
Project Start
2014-09-15
Project End
2019-08-31
Budget Start
2014-09-15
Budget End
2019-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$2,377,500
Indirect Cost
$877,500
Name
Case Western Reserve University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Cai, Xiaoshu; Chen, Yang; Gao, Zhen et al. (2016) Explore Small Molecule-induced Genome-wide Transcriptional Profiles for Novel Inflammatory Bowel Disease Drug. AMIA Jt Summits Transl Sci Proc 2016:22-31
Xu, Rong; Wang, QuanQiu (2016) A genomics-based systems approach towards drug repositioning for rheumatoid arthritis. BMC Genomics 17 Suppl 7:518
Chen, Yang; Xu, Rong (2016) Phenome-based gene discovery provides information about Parkinson's disease drug targets. BMC Genomics 17 Suppl 5:493
Chen, Yang; Gao, Zhen; Wang, Bingcheng et al. (2016) Towards precision medicine-based therapies for glioblastoma: interrogating human disease genomics and mouse phenotypes. BMC Genomics 17 Suppl 7:516
Xu, Rong; Wang, QuanQiu (2016) Towards understanding brain-gut-microbiome connections in Alzheimer's disease. BMC Syst Biol 10 Suppl 3:63
Xu, Rong; Wang, QuanQiu (2015) PhenoPredict: A disease phenome-wide drug repositioning approach towards schizophrenia drug discovery. J Biomed Inform 56:348-55
Xu, Rong; Wang, QuanQiu (2015) Combining automatic table classification and relationship extraction in extracting anticancer drug-side effect pairs from full-text articles. J Biomed Inform 53:128-35
Xu, Rong; Wang, QuanQiu (2015) tcTKB: an integrated cardiovascular toxicity knowledge base for targeted cancer drugs. AMIA Annu Symp Proc 2015:1342-51
Xu, Rong; Wang, QuanQiu (2015) Large-scale automatic extraction of side effects associated with targeted anticancer drugs from full-text oncological articles. J Biomed Inform 55:64-72
Wang, QuanQiu; Xu, Rong (2015) DenguePredict: An Integrated Drug Repositioning Approach towards Drug Discovery for Dengue. AMIA Annu Symp Proc 2015:1279-88

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