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 #
5U19GM061390-15
Application #
8689080
Study Section
Special Emphasis Panel (ZRG1-GGG-M)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
15
Fiscal Year
2014
Total Cost
$936,115
Indirect Cost
$290,104
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Chen, Ligong; Shu, Yan; Liang, Xiaomin et al. (2014) OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. Proc Natl Acad Sci U S A 111:9983-8
Smith, Robin P; Eckalbar, Walter L; Morrissey, Kari M et al. (2014) Genome-wide discovery of drug-dependent human liver regulatory elements. PLoS Genet 10:e1004648
VanderMeer, Julia E; Lozano, Reymundo; Sun, Miao et al. (2014) A novel ZRS mutation leads to preaxial polydactyly type 2 in a heterozygous form and Werner mesomelic syndrome in a homozygous form. Hum Mutat 35:945-8
Clancy, J P; Johnson, S G; Yee, S W et al. (2014) Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for ivacaftor therapy in the context of CFTR genotype. Clin Pharmacol Ther 95:592-7
Chhibber, A; Mefford, J; Stahl, E A et al. (2014) Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance). Pharmacogenomics J 14:336-42
Erwin, Genevieve D; Oksenberg, Nir; Truty, Rebecca M et al. (2014) Integrating diverse datasets improves developmental enhancer prediction. PLoS Comput Biol 10:e1003677
VanderMeer, Julia E; Smith, Robin P; Jones, Stacy L et al. (2014) Genome-wide identification of signaling center enhancers in the developing limb. Development 141:4194-8
Larregieu, Caroline A; Benet, Leslie Z (2014) Distinguishing between the permeability relationships with absorption and metabolism to improve BCS and BDDCS predictions in early drug discovery. Mol Pharm 11:1335-44
Kim, Mee J; Oksenberg, Nir; Hoffmann, Thomas J et al. (2014) Functional characterization of SIM1-associated enhancers. Hum Mol Genet 23:1700-8
Martin, M A; Hoffman, J M; Freimuth, R R et al. (2014) Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 update. Clin Pharmacol Ther 95:499-500

Showing the most recent 10 out of 44 publications