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
Belur Nagaraj, Anil; Joseph, Peronne; Kovalenko, Olga et al. (2018) Evaluating class III antiarrhythmic agents as novel MYC targeting drugs in ovarian cancer. Gynecol Oncol 151:525-532
Wang, QuanQiu; Li, Li; Xu, Rong (2018) A systems biology approach to predict and characterize human gut microbial metabolites in colorectal cancer. Sci Rep 8:6225
Nagaraj, A B; Wang, Q Q; Joseph, P et al. (2018) Using a novel computational drug-repositioning approach (DrugPredict) to rapidly identify potent drug candidates for cancer treatment. Oncogene 37:403-414
Zheng, Chunlei; Xu, Rong (2018) Large-scale mining disease comorbidity relationships from post-market drug adverse events surveillance data. BMC Bioinformatics 19:500
Wang, QuanQiu; Xu, Rong (2017) MetabolitePredict: A de novo human metabolomics prediction system and its applications in rheumatoid arthritis. J Biomed Inform 71:222-228
Cai, Xiaoshu; Chen, Yang; Zheng, Chunlei et al. (2017) Interrogating Patient-level Genomics and Mouse Phenomics towards Understanding Cytokines in Colorectal Cancer Metastasis. AMIA Jt Summits Transl Sci Proc 2017:227-236
Wang, QuanQiu; Xu, Rong (2017) Drug repositioning for prostate cancer: using a data-driven approach to gain new insights. AMIA Annu Symp Proc 2017:1724-1733
Gao, Zhen; Chen, Yang; Cai, Xiaoshu et al. (2017) Predict drug permeability to blood-brain-barrier from clinical phenotypes: drug side effects and drug indications. Bioinformatics 33:901-908
Wang, QuanQiu; McCormick, Thomas S; Ward, Nicole L et al. (2017) Combining mechanism-based prediction with patient-based profiling for psoriasis metabolomics biomarker discovery. AMIA Annu Symp Proc 2017:1734-1743
Chen, Yang; Xu, Rong (2017) Context-sensitive network-based disease genetics prediction and its implications in drug discovery. Bioinformatics 33:1031-1039

Showing the most recent 10 out of 31 publications