AND SPECIFIC AIMS: NETWORK RESOURCE This component of the Mayo Clinic PGRN renewal application represents a request for the funding of a """"""""Network Resource"""""""" designed to provide the entire PGRN with access to the latest techniques In the rapidly evolving field of """"""""Next Generation"""""""" DNA sequencing. Access would be provided through a recurring, peer-reviewed process available to all PGRN Centers similar to the current """"""""PGRN-RIKEN"""""""" process for obtaining access to pharmacogenomic GWAS genotyping through the PGRN-RIKEN collaboration. This proposed """"""""PGRN Nehwork Resource"""""""" is one of three coordinated applications from current PGRN Centers, all with similar goals - clearly indicating an unmet need in pharmacogenomic research - a need emphasized by the letters of support from current PGRN Centers that are attached to this application. Those letters were sent by eight different PGRN research centers. Although pharmacoqenomics has always required access to DNA sequencing, that need has been accentuated bv recent dramatic changes in DNA seguencing technology and bv the eguallv dramatic outcomes of the application of genome-wide approaches to pharmacogenomics. Each of these proposals is designed to provide a """"""""link"""""""" between the PGRN and a large, experienced Genomics Center with expertise in both the application and the evaluation of DNA sequencing technology. The issue is not whether pharmacogenomics as a discipline requires access to the very latest in rapidly evolving DNA sequencing techniques, but only how to achieve that goal in a way that will best advance the science while being affordable and open to all PGRN Centers. Specifically, the Mayo PGRN is proposing that a formal collaborative relationship be established with the Baylor College of Medicine (BCM)-Human Genome Sequencing Center (HGSC), one of three NHGRIsupported large genome centers - with an open, protocol-based selection process similar to the well established and highly successful PGRN-RIKEN process for the selection of PGRN pharmacogenomic GWAS genotyping projects performed in collaboration with RIKEN. The initial focus of the Mayo PGRN-sponsored """"""""Next Generation"""""""" DNA sequencing Network Resource would be on sequencing large contiguous regions of the genome. In some cases, this will involve complete resequencing of large genes or tandemly repeated gene families or even entire gene families, e.g., the """"""""CYPome"""""""", all cytochrome P450 genes. In other cases, it wilt involve focused resequencing across """"""""SNP signals"""""""" observed during pharmacogenomic GWA studies - in many cases, GWA studies made possible by the PGRN-RIKEN collaboration, thus building on a foundation established by that very successful program. Since the review panel for these applications will evaluate a series of Network Resource applications for access to Next Generation DNA sequencing, it should be emphasized that the Mayo PGRN looks upon these efforts as complementary. Therefore, it is possible that reviewers may conclude that some """"""""combination"""""""" of these proposals should be supported. All of these proposals share; ? A recognition of the critical need for access to rapidly evolving DNA sequencing techniques in order to advance the science of pharmacogenomics. ? A recognition that established Genome Centers have the requisite experience, expertise and infrastructure required to make this effort succeed. ? A recognition that the """"""""process"""""""" for access to Next Generation DNA sequencing will have to be open to all PGRN centers, based on scientific significance and feasibility. The cost associated with these studies would be covered primarily by funding available to the """"""""Network Resource"""""""".

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-GGG-M)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mayo Clinic, Rochester
United States
Zip Code
Cairns, Junmei; Fridley, Brooke L; Jenkins, Gregory D et al. (2018) Differential roles of ERRFI1 in EGFR and AKT pathway regulation affect cancer proliferation. EMBO Rep 19:
Liu, Duan; Qin, Sisi; Ray, Bamiki et al. (2018) Single Nucleotide Polymorphisms (SNPs) Distant from Xenobiotic Response Elements Can Modulate Aryl Hydrocarbon Receptor Function: SNP-Dependent CYP1A1 Induction. Drug Metab Dispos 46:1372-1381
Hanson, Casey; Cairns, Junmei; Wang, Liewei et al. (2018) Principled multi-omic analysis reveals gene regulatory mechanisms of phenotype variation. Genome Res 28:1207-1216
Gonzalez-Mercado, Velda J; Fridley, Brooke L; Saligan, Leorey N (2018) Sestrin family of genes and their role in cancer-related fatigue. Support Care Cancer 26:2071-2074
Wang, Liewei; Ingle, James; Weinshilboum, Richard (2018) Pharmacogenomic Discovery to Function and Mechanism: Breast Cancer as a Case Study. Clin Pharmacol Ther 103:243-252
Athreya, Arjun P; Gaglio, Alan J; Cairns, Junmei et al. (2018) Machine Learning Helps Identify New Drug Mechanisms in Triple-Negative Breast Cancer. IEEE Trans Nanobioscience 17:251-259
Sá, Ana Caroline C; Webb, Amy; Gong, Yan et al. (2018) Blood pressure signature genes and blood pressure response to thiazide diuretics: results from the PEAR and PEAR-2 studies. BMC Med Genomics 11:55
Ho, Ming-Fen; Lummertz da Rocha, Edroaldo; Zhang, Cheng et al. (2018) TCL1A, a Novel Transcription Factor and a Coregulator of Nuclear Factor ?B p65: Single Nucleotide Polymorphism and Estrogen Dependence. J Pharmacol Exp Ther 365:700-710
Singh, Sonal; Wang, Zhiying; Shahin, Mohamed H et al. (2018) Targeted sequencing identifies a missense variant in the BEST3 gene associated with antihypertensive response to hydrochlorothiazide. Pharmacogenet Genomics 28:251-255
Liu, Duan; Ray, Balmiki; Neavin, Drew R et al. (2018) Beta-defensin 1, aryl hydrocarbon receptor and plasma kynurenine in major depressive disorder: metabolomics-informed genomics. Transl Psychiatry 8:10

Showing the most recent 10 out of 163 publications