The Functional Genomics Research Team brings together a world-class group of experts with diverse backgrounds in membrane transporters and in transcriptional and regulatory genomics. The UCSF investigators with expertise in transporter biology include Kathleen Giacomini, Deanna Kroetz and Leslie Benet who participated in the last funding cycle. They made significant contributions in characterizing the function of amino acid variants and basal promoter regions of ABC and SLC membrane transporters. In this funding cycle, these investigators will continue their active role and expertise to direct the studies of characterizing the function of non-coding region (promoter, UTRs region and enhancer region) variants of membrane transporters in cells and mouse models. In planning the renewal application, the group felt that they needed to phenotypically characterize more variants and to extend their studies beyond amino acid variants and basal promoter region variants. To this end, Nadav Ahituv was recruited in the forth funding year of the last funding cycle to the project to complement and extend the existing expertise in transcriptional and gene regulation. His expertise and knowledge in comparative genomic strategies and regulatory element analysis have led to discoveries of regulatory sequence variation in the non-coding regions of genes associated with human congenital abnormalities and other clinically relevant phenotypes. Collectively, the Functional Genomics Research Team provides outstanding diverse and complementary expertise in experimental methods to characterize and to map the functional regions and the sequence variants of these regions of the membrane transporters in the upcoming five years. In addition to the investigators mentioned above, Hobart Harris and Xin Chen will support our pharmacogenomics studies with their individual expertise in initiating and setting standard protocols to accrue and to bank kidney and liver tissues. These unique and ethnically diverse kidney and liver tissue samples are valuable for determining transporter expressions and also in identifying and supporting the findings from our functional studies. This team will also work closely with the computational genomics team to identify key regulatory and functional regions in the transporter genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19GM061390-14
Application #
8546202
Study Section
Special Emphasis Panel (ZRG1-GGG-M)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
14
Fiscal Year
2013
Total Cost
$924,113
Indirect Cost
$286,494
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Yee, S W; Giacomini, M M; Hsueh, C-H et al. (2016) Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1. Clin Pharmacol Ther 100:524-536
Zhou, Kaixin; Yee, Sook Wah; Seiser, Eric L et al. (2016) Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin. Nat Genet 48:1055-9
Zheng, Yi; Chen, Xijing; Benet, Leslie Z (2016) Reliability of In Vitro and In Vivo Methods for Predicting the Effect of P-Glycoprotein on the Delivery of Antidepressants to the Brain. Clin Pharmacokinet 55:143-67
Benet, Leslie Z; Hosey, Chelsea M; Ursu, Oleg et al. (2016) BDDCS, the Rule of 5 and drugability. Adv Drug Deliv Rev 101:89-98
Rotroff, Daniel M; Oki, Noffisat O; Liang, Xiaomin et al. (2016) Pharmacometabolomic Assessment of Metformin in Non-diabetic, African Americans. Front Pharmacol 7:135
Yee, S W; Momozawa, Y; Kamatani, Y et al. (2016) Genomewide Association Studies in Pharmacogenomics: Meeting Report of the NIH Pharmacogenomics Research Network-RIKEN (PGRN-RIKEN) Collaboration. Clin Pharmacol Ther 100:423-426
Li, M; Seiser, E L; Baldwin, R M et al. (2016) ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia. Pharmacogenomics J :
Eclov, Rachel J; Kim, Mee J; Smith, Robin P et al. (2016) In Vivo Hepatic Enhancer Elements in the Human ABCG2 Locus. Drug Metab Dispos :
Hibma, Jennifer E; Zur, Arik A; Castro, Richard A et al. (2016) The Effect of Famotidine, a MATE1-Selective Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Metformin. Clin Pharmacokinet 55:711-21
Yuan, Bo; Yoshino, Yuta; Fukushima, Hisayo et al. (2016) Multidrug resistance-associated protein 4 is a determinant of arsenite resistance. Oncol Rep 35:147-54

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