“Combined Approach to Broadly Protective AIDS Vaccines” (NIH; PI: Shiu-Lok Hu): to design effective vaccines for HIV and AIDS.
“Core B: Recombinant Protein Immunogens” (Dana-Farber Cancer Institute; PI: Shiu-Lok Hu): to provide investigators in Projects 2 and 3 with recombinant subunit proteins, including HIV-1 clade C gp160, SIV Gag-Pol particles, as well as recombinant SIVmac239 Nef protein.
“Drug Transport at the CNS Barriers” (NIH; PI: Joanne Wang): This project focuses on determining the molecular mechanism, anatomical location and in vivo consequence of PMAT in brain transport of organic cation neurotoxins and drugs. We hypothesized that PMAT is localized at the apical membrane of the choroidal epithelium and functions in removing organic cations from the CSF.
“Effects of Xenobiotics on CYP26 Activity and Retinoic Acid Homeostasis” (NIH; PI: Nina Isoherranen): These studies will contribute to the basic understanding of the biological function of CYP26A1, two understudied P450 enzymes that are essential for life. The results obtained will form a basis for future clinical and mechanistic studies on how these two enzymes function to maintain human health.
“Effects of Xenobiotics on CYP26 Activity and Retinoic Acid Homeostasis [ARRA]” (NIGMS; PI: Nina Isoherranen): The overall goal of these studies is to determine the role of autocrine and paracrine components of RA signaling and determine how xenobiotic-CYP26 interactions may cause adverse or therapeutic effects.
“Genetic and Hormonal regulation of Human CYP3A” (NIGMS; PI: Kenneth Thummel): the overall objectives are to determine whether 1,25-- (OH)2-D3 regulates the expression of cyp3A4 in the human small intestine in vivo, and whether the administration of the drugs that affect CYP34A function through enzyme induction or inhibition alter the synthesis and function of intestinal calcium transport proteins through changes in 1,25-(OH)2-D3 disposition within the mucosal enterocyte.
“Genetic and Hormonal Regulation of Human CYP3A [suppl]” (NIGMS; PI: Kenneth Thummel): The experimental plan described in this administrative supplement is designed to accelerate the pace of scientific research by addressing two partial bottlenecks to completion of the specific aims: (1) a challenging assay development for measurement of CYP-selective, 24R and 23R,25-dihydroxy vitamin D3 metabolites and (2) a slower than desirable recruitment of subjects for duodenal biopsy studies.
“Glycan modification, CD4 independence and Env immunogenicity (Suppl)” (NIAID; PI: Shiu-Lok Hu): We propose to further define the nature of the cross-relative neutralizing antibody response elicited by glycan mutated Env and to examine the basis and the general applicability of this observation.
“In-Vitro to In-Vivo prediction of drug interactions involving CYP3A time-dependent inactivation” (Simcyp Ltd; PI: Jashvant Unadkat): The ability to reliably predict in-vivo DDIs from in-vitro data is a major focus of the pharmaceutical industry as well as Simcyp. These interactions are relatively well predicted when the DDI is a result of competitive inhibition. A similar approach has been employed for the prediction of TDI (time dependent inactivation) DDIs. Although this approach has had some successes (e.g. CYP2D6), many of the TDI DDIs are less accurately predicted (e.g. CYP3A). Here we propose methods to increase the accuracy of these predications.
“Mechanism of Drug Transport by BCRP/ABCG2” (NIH; PI: Qingcheng Mao): Long term goal is to explore the molecular mechanism of BCRP. To achieve this goal, site directed mutagenesis and functional characterization of BCRP mutants, protein purification and structure determination will be employed.
“Nucleoside Transporters: disposition of Nucleoside drugs” (NIH; PI: Jashvant Unadkat): The long term goals are to determine the role of equilibrative nucleoside transporters in the in vitro and in vivo mitochondrial toxicity of nucleoside drugs such as FIAU.
“P-glycoprotein and Alzheimer's Disease” (NIA; PI: Jashvant Unadkat): Compare P-gp activity at the BBB in Alzheimer patients and in age-matched cognitively normal volunteers using non invasive technology, positron emission tomography. Our studies will utilize an innovative, noninvasive PET imaging technique, developed by our laboratories, to measure P-gp activity at the BBB of patients with AD and age matched cognitively normal volunteers.
“pHresponsive anti-HIV nanoparticles” (NIH; PI: Rodney Ho): Test the following hypothesis: a pH responsive anti HIV nano-lipid complex delivery system trageted to lymphoid tissues and HIV host cells will greatly improve cell and tissue selectivity, and thus overcomes drug insufficiency and will maximally inhibit viral replication and disease progression.
“Pop Kinetics HCT- Staff Assignment” (FHCRC; PI: Joanne Wang): Staff assignment for Dr. Joanne Wang's participation on the "Population Pharmacokinetics/Pharmacodynamics in Nonablative Stem Cell Recipients" grant from the Fred Hutchinson Cancer Research Institute with a PI Dr. Jeannine McCune. Dr. Wang is a co-Investigator on the project. On this project she will work on study design and drug interactions as well as data analysis and study publications.
“Toward an HIV-1 macaque model” (Baylor College of Medicine; PI: Shiu-Lok Hu): to develop a human immunodeficiency virus type 1 (HIV-1)-macaque model of infection and disease.
“Washington National Primate Research Center FY48” (NCRR; PI: Shiu-Lok Hu): The major goal is to support a broad based research resources program affording biomedical scientist the opportunity to conduct research using nonhuman primates for human health related problems.
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