The Pharmacogenomics Center of the University of California, Sam Francisco: at the interface of genomics, biological mechanism and drug therapy

Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, San Francisco, CA, USA.
Pharmacogenomics (Impact Factor: 3.22). 10/2009; 10(10):1569-76. DOI: 10.2217/pgs.09.119
Source: PubMed


The Pharmacogenomics Center of the University of California, San Francisco (CA, USA) fosters research and educational activities focused on the genomic basis for variation in drug response. Investigators in the Center conduct multidisciplinary and multicenter research on a diverse array of clinically used drugs with the goal of understanding the genetic factors that contribute to variation in therapeutic and adverse drug response. The Center houses the large NIH-supported Pharmacogenomics of Membrane Transporters Project, which is a leader in understanding genetic variation in membrane transporters that are important in clinical drug response. Center investigators study racially and ethnically diverse populations, are pioneers in the education of PharmD, MD and PhD students in pharmacogenomics, and have led the establishment of unique graduate and postdoctoral training programs focused on pharmacogenomics. A key emphasis of the Center is on biological mechanisms with a goal of facilitating the development of safer and more effective medications.

Download full-text


Available from: Nadav Ahituv, Jan 04, 2014
  • Source
    • "Solute carriers are a group of approximately 400 biomedically important membrane proteins that control the uptake and efflux of solutes, including essential cellular compounds and therapeutic drugs (45). Numerous variants that are important for clinical drug response have been identified in solute carriers by the Pharmacogenomics of Membrane Transporters project (PMT) at UCSF (46). Solute carriers can share similar structural features despite weak sequence similarities. "
    [Show abstract] [Hide abstract]
    ABSTRACT: ModBase ( is a database of annotated comparative protein structure models. The models are calculated by ModPipe, an automated modeling pipeline that relies primarily on Modeller for fold assignment, sequence–structure alignment, model building and model assessment ( ModBase currently contains 10 355 444 reliable models for domains in 2 421 920 unique protein sequences. ModBase allows users to update comparative models on demand, and request modeling of additional sequences through an interface to the ModWeb modeling server ( ModBase models are available through the ModBase interface as well as the Protein Model Portal ( Recently developed associated resources include the SALIGN server for multiple sequence and structure alignment (, the ModEval server for predicting the accuracy of protein structure models (, the PCSS server for predicting which peptides bind to a given protein ( and the FoXS server for calculating and fitting Small Angle X-ray Scattering profiles (
    Nucleic Acids Research 01/2011; 39(Database issue):D465-74. DOI:10.1093/nar/gkq1091 · 9.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biologists seek an accurate description of the biological world. Engineers do not describe things. Instead they design devices that they then build and test. Bioengineers bring these disparate disciplines together in two ways that are conceptually very different. In the past, bioengineering has meant designing, building and testing mechanical devices that operate on biological tissue. A rapidly growing branch of bioengineering, however, applies biological principles to design, build and test novel forms of cells that execute reliably a desired function. We offer a brief review of recent developments in both forms of bioengineering and examine their potential value for Vietnamese bioengineers.
    The Third International Conference on the Development of Biomedical Engineering in Vietnam, 12/2009: pages 14-18;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed RNA-seq and ChIP-seq using antibodies against the pregnane X receptor (PXR) and three active regulatory marks (p300, H3K4me1, H3K27ac) on primary human hepatocytes treated with rifampin or vehicle control. Rifampin and PXR were chosen since they are part of the CYP3A4 pathway, which is known to account for the metabolism of more than 50% of all prescribed drugs. We selected 227 proximal promoters for genes with rifampin-dependent expression or nearby PXR/p300 occupancy sites and assayed their ability to induce luciferase in rifampin-treated HepG2 cells, finding only 10 (4.4%) that exhibited drug-dependent activity. As this result suggested a role for distal enhancer modules, we searched more broadly to identify 1,297 genomic regions bearing a conditional PXR occupancy as well as all three active regulatory marks. These regions are enriched near genes that function in the metabolism of xenobiotics, specifically members of the cytochrome P450 family. We performed enhancer assays in rifampin-treated HepG2 cells for 42 of these sequences as well as 7 sequences that overlap linkage-disequilibrium blocks defined by lead SNPs from pharmacogenomic GWAS studies, revealing 15/42 and 4/7 to be functional enhancers, respectively. A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity. Combined, our results further suggest that enhancers are the predominant targets of rifampin-induced PXR activation, provide a genome-wide catalog of PXR targets and serve as a model for the identification of drug-responsive regulatory elements.
    PLoS Genetics 10/2014; 10(10). DOI:10.1371/journal.pgen.1004648 · 7.53 Impact Factor