This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): Billions of prescriptions are written each year in the hopes of improving health and preventing disease in millions of Americans. Unfortunately, these medications do not work as hoped in everyone, and others suffer from side effects, leading to substantial morbidity and mortality. Although genetic variability in the response to medications has been known for decades to play a critical role in limiting the efficacy and safety of drugs, recent advances in genetics, bioinformatics, pharmacology, epidemiology, and biostatistics have paved the way for tremendous gains in understanding how genetic variability can alter drug response. Despite this promise, the nature of gene-drug interactions is complex, and progress in the field has been hampered by the lack of a true interdisciplinary approach. A complete understanding of the genetic basis for variable responses to medications and appropriate application of this information in human populations will come only through a coordinated and sustained collaboration among the disciplines of genetics, bioinformatics, pharmacology, epidemiology, biostatistics, and bioethics in a new interdisciplinary field that we call Human Pharmacogenomic Epidemiology (HPE). HPE is not simply the merger of multiple disciplines, working in parallel or sequence, but rather a new paradigm of research that must develop novel ways of working synergistically to address the scientific, logistical, and intellectual barriers to interdisciplinary research. In this application, a group of experienced investigators from each of these disciplines, working within an enriched and supportive academic environment, proposes to develop an interdisciplinary collaboration whose aims are to develop unique and sustainable approaches to solving the significant and complex biomedical problem of variable drug response by developing strategies targeted at all three barriers to interdisciplinary research: 1) Scientific: by developing study design and statistical methods aimed at solving problems of the complex, high-dimensional nature of genetic influences on response to medications, 2) Logistical: by developing new strategies that improve the coordination and efficiency of HPE research, and 3) Intellectual: by designing innovative and sustainable approaches to improve the appreciation among the disciplines of each others' scientific context, opportunities offered, and distinct methods and languages.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR020741-03
Application #
7382219
Study Section
Special Emphasis Panel (ZRR1-BT-8 (01))
Project Start
2006-08-01
Project End
2007-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
3
Fiscal Year
2006
Total Cost
$560,726
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Desai, Krupali; Mao, Jun J; Su, Irene et al. (2013) Prevalence and risk factors for insomnia among breast cancer patients on aromatase inhibitors. Support Care Cancer 21:43-51
Friedman, Claire F; DeMichele, Angela; Su, H Irene et al. (2012) Vitamin d deficiency in postmenopausal breast cancer survivors. J Womens Health (Larchmt) 21:456-62
Mao, Jun J; Su, H Irene; Feng, Rui et al. (2011) Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors. Breast Cancer Res 13:R8
Schelleman, Hedi; Brensinger, Colleen M; Chen, Jinbo et al. (2010) New genetic variant that might improve warfarin dose prediction in African Americans. Br J Clin Pharmacol 70:393-9
Platt, Alec B; Localio, A Russell; Brensinger, Colleen M et al. (2010) Can we predict daily adherence to warfarin?: Results from the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study. Chest 137:883-9
Guo, Mengye; Heitjan, Daniel F (2010) Multiplicity-calibrated Bayesian hypothesis tests. Biostatistics 11:473-83
Hammons, Andrea L; Summers, Carolyn M; Woodside, Jayne V et al. (2009) Folate/homocysteine phenotypes and MTHFR 677C>T genotypes are associated with serum levels of monocyte chemoattractant protein-1. Clin Immunol 133:132-7
International Warfarin Pharmacogenetics Consortium; Klein, T E; Altman, R B et al. (2009) Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 360:753-64
Mitchell, Laura E; Morales, Megan; Khartulyari, Stefanie et al. (2009) Folate and homocysteine phenotypes: Comparative findings using research and clinical laboratory data. Clin Biochem 42:1275-81
Guéant, Jean-Louis; Guéant-Rodriguez, Rosa-Maria; Cornejo-Garcia, Jose-Antonio et al. (2009) Gene variants of IL13, IL4, and IL4RA are predictors of beta-lactam allergy. J Allergy Clin Immunol 123:509; author reply 509-10

Showing the most recent 10 out of 21 publications