The effects of glutathione supplementation on the attenuation of the markers for VPA-induced toxicities were investigated. VPA toxicity was assessed by markers such as 2′,7′-dichlorofluorescein formation (oxidative stress), BODIPY 558/568 C12 accumulation (steatosis), lactate dehydrogenase release (necrosis), and cellular content of total glutathione (antioxidant status). Currently an Assistant Professor at the UBC Institute for the Oceans and Fisheries, Tom works on quantitative solutions to critical fishery management problems. Overall, these findings add significant knowledge to the role of VPA and its metabolites in the induction of hepatotoxicity and how VPA is metabolized in humans.View record, Relatively little is known about the expression, localization and regulation of rat testicular xenobiotic-metabolizing enzymes, including cytochrome P450s (CYP) and microsomal epoxide hydrolase (mEH), which are involved in the metabolism of xenobiotics including drugs and toxicants, and of endobiotics such as steroid hormones and prostaglandins. Burroughs Wellcome Fund (U.S.A.). Furthermore, VPA-associated GSH depletion appeared not to be a factor in the mitochondrial dysfunction, but may play a partial role in VPA-induced cytotoxicity. She held a Canada Research Chair (Tier 2) in Disaster Management and Urban Sustainability from 2004 to 2013. Canadian Institute of Health Research and Rx&D Health Research Foundation. Demonstrate that you are familiar with their research: Convey the specific ways you are a good fit for the program. Other studies include elucidating the cellular and molecular mechanisms by which drugs and other chemicals activate constitutive androstane receptor and pregnane X receptor, and identifying the various factors that regulate the expression and function of these nuclear receptors. Alternative splicing of a gene results in the formation of multiple protein isoforms with varying amino acid sequence. Chang TKH. drugs, environmental chemicals) and endogenous substances (e.g. (604) 822-7795 If you have reviewed some of this faculty member's publications, understand their research interests and have reviewed the admission requirements, you may, Pregnane X Receptor and Constitutive Androstane Receptor Activation by Non-nucleoside HIV-1 Reverse Transcriptase Inbibitors (2016), The effect of digestion and drug load on absorption of poorly water soluble drugs from self-nanoemulsifying drug delivery systems (SNEDDS) (2016), Valproic acid biotransformation and toxicity in sandwich-cultured rat hepatocytes (2014), Valproic Acid: Mechanisms of Hepatotoxicity and Reaction Phenotyping (2010), Constitutive expression of xenobiotic-metabolizing enzymes in rat testis: Immunochemical characterization and regulation by 17-beta-estradiol benzoate and bisphenol A (2013), Pharmaceutical Sciences, Master of Science, Pharmaceutical Sciences, Doctor of Philosophy, submit a contact request to this supervisor, Promoting Excellence in Graduate Programs, Supporting Student Development and Success, Familiarize yourself with program requirements. Read up on the faculty members in the program and the research being conducted in the department. Thomas Chang (UBC Professor): Pharmacology, Nuclear Receptor, Drug-Metabolizing Enzymes, Cytochrome P450, Gene Expression, Gene regulation To further understand PXR regulation by rilpivirine, the role of microRNA in rilpivirine activation of PXR was investigated. (E)-2-ene-VPA, which is a β-oxidation metabolite of VPA, was also included in the experiments concerning (E)-2,4-diene-VPA, as it formed relatively large amounts of (E)-2,4-diene-VPA. Stephanie Chang (UBC Professor): natural disasters, risk, resilience, climate change adaptation, infrastructure systems, earthquakes, coastal hazards 1998. Shawn Chang, 3rd year Science student (Combined Honours in Biochemistry and Forensic Science) You can learn what you really love “I think the biggest difference between uni and high school is that in university, you have the autonomy to choose topics that you actually want to learn about. Immunohistochemical analysis of tissue sections prepared from frozen testis indicated that CYP1B1, CYP2A1 and CYP17A1 were localized in interstitial cells, but not in seminiferous tubules, whereas mEH and POR were localized in both interstitial cells and in seminiferous tubules. In order to examine precipitation of poorly water soluble drugs dosed in LbDDS invivo the gastric and intestinal content of rats was examined for precipitated crystalline drug using XRPD and PLM. Evening classes at UBC and the January 15th preview of The Changeling have been cancelled due to current and expected extreme weather conditions in Vancouver.Please visit ubc.ca for further updates. 2007-2012. Clinical use of VPA is associated with a rare, but possibly fatal, idiosyncratic hepatotoxicity. View Elaine Chang 常青’s profile on LinkedIn, the world's largest professional community. Overall, the results of the present study add value to the existing knowledge on the role of reactive metabolites of VPA in VPA hepatotoxicity. Convey the specific ways the program/lab/faculty member is a good fit for the research you are interested in/already conducting. Dr. Chang also completed the faculty certificate program on Teaching and Learning in Higher Education at UBC. Cane Kong has uploaded 2266 photos to Flickr. Liquidity Constrained Exporters (Thomas Chaney) November 2016, 72: 141-54 | | Journal of Economic Dynamics and Control ©2016 by Elsevier. Our findings in SCRH indicated that (E)-2,4-diene-VPA was the only exogenously administered metabolite tested that was consistently more toxic than VPA. The study revealed that precipitation onlywas evident in the stomach, thus precipitation in the intestinal in vitro modelmay be an artifact and may require the addition of an in vitro gastric digestion step to be predictive in vivo.View record, Valproic acid (VPA) is a widely prescribed broad-spectrum antiepileptic drug. The mechanism of VPA hepatotoxicity is not known, but it may involve reactive metabolites of VPA. UBC courses are eligible for credit towards a UBC degree program on either campus. Reporter gene assays revealed a functional hsa-miR-18a-5p microRNA recognition element in the 3′-untranslated region of PXR. Based on the modulatory experiments with phenobarbital and 1-aminobenzotriazole, in situ generated (E)-2,4-diene-VPA did not appear to contribute to VPA toxicity in sandwich-cultured rat hepatocytes. steroid hormones, vitamins, bile acids). To rebook or refund preview tickets, please contact box.office@ubc… Constitutive expression of these rat testicular enzymes was suppressed by exogenous administration of 17β-estradiol and BPA.View record, Member of G+PSView explanation of statuses. Professor and Associate Dean, Graduate and Postdoctoral Studies, Office of the Associate Dean, Graduate and Postdoctoral Studies, Bachelor of Pharmaceutical Sciences Degree, Continuing Pharmacy Professional Development, Data Analytics, Statistics and Informatics, Nuclear Receptor Regulation of Hepatic Cytochrome P450 Enzymes, The xenobiotic sensing pregnane X receptor regulates tissue damage and inflammation triggered by C difficile toxins, Pregnane X Receptor Activation Triggers Rapid ATP Release in Primed Macrophages That Mediates NLRP3 Inflammasome Activation, Negative Regulation of Human Pregnane X Receptor by MicroRNA-18a-5p: Evidence for Suppression of MicroRNA-18a-5p Expression by Rifampin and Rilpivirine, Cell-based and in silico evidence against quercetin and structurally-related flavonols as activators of vitamin D receptor. Story submitted by. 74, pp. Google Scholar; BibTex EB and BPA did not produce a general down-regulation of testicular protein expression because neither of these chemicals decreased calnexin protein (endoplasmic reticulum marker) levels. Thomas SchneiderProfessor of Egyptology and Near Eastern Studiesthomas.schneider@ubc.cawork phone: 604-827-4316 "Research Career Award". GSH may serve a protective role against VPA-induced oxidative stress in SCRH. The contribution of the CYP- and UGT-mediated biotransformation of VPA in VPA-induced toxicity was also examined. He pursued his postdoctoral studies in the Division of Cancer Pharmacology at the Dana-Farber Cancer Institute and the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. Join Facebook to connect with Thomas Chang and others you may know. MicroRNAs are small non-coding RNAs that are post-transcriptional regulators causing mRNA degradation or translational repression by binding to complementary regions in target mRNA. Elaine has 6 jobs listed on their profile. According to the findings with β-naphthoflavone and borneol, in situ generated VPA-G did not appear to be toxic to sandwich-cultured rat hepatocytes and was unlikely to contribute to the hepatocyte toxicity of VPA. Thomas Hu. As shown in Study 1, immunoblot analysis of testicular microsomes prepared from untreated rats revealed the presence of CYP1B1, CYP2A1, CYP17A1, NADPH-cytochrome P450 reductase (POR) and mEH, and absence of CYP1A1, CYP1A2, CYP2B1, CYP2E1, CYP2D1, CYP2D2, CYP2C6, CYP2C7, CYP2C11, CYP2C12, CYP2C13, CYP3A1, CYP3A2, CYP4A1, CYP4A2 and CYP4A3. In cell-based assays, over-expression of hsa-miR-18a-5p by transfecting LS180 human colon adenocarcinoma cells with a mimic of hsa-miR-18a-5p decreased PXR mRNA and protein expression. Be sure to visit the, Check whether the program requires you to seek commitment from a supervisor prior to submitting an application. "Research Scholar Award". For some programs this is an essential step while others match successful applicants with faculty members within the first year of study. The Southern Medical Program (SMP) at UBC Okanagan campus is educating the next generation of doctors, fostering new discoveries, and building new pathways to improve health for communities across the Interior Health region. Experience. staff. The Changeling by Thomas Middleton and William Rowley Directed by MFA Director Luciana Silvestre Fernandes. This means credits from a different campus will not be converted to transfer credit but may have a course equivalency. "Killam Faculty Research Fellowship". Credits that have an established equivalent between campuses can be used to satisfy course-specific degree requirements. Address the faculty members by name. She held a Canada Research Chair (Tier 2) in Disaster Management and Urban Sustainability from 2004 to 2013. People & Change: Thomas Veal October 24, 2019. Familiarize yourself with their work, read their recent publications and past theses/dissertations that they supervised. WEATHER ADVISORY! In contrast, over-expression of hsa-miR-18a-5p decreased PXR mRNA expression and CYP3A4 inducibility by rilpivirine and rifampin. British Columbia Health Research Foundation. The traditional interpretation of data from the lipolysis model is that the solubilized fraction of drug is available for absorption, whereas the precipitated fraction needs to be re-dissolved in order to be absorbed which is believed to lower the bioavailability. Do not send non-specific, mass emails to everyone in the department hoping for a match. CORONAVIRUS (COVID-19): please review UBC’s general information and FAQs and G+PS's graduate student-specific information. Using a sandwich-cultured rat hepatocyte model, the present work investigated the toxicity of two specific VPA metabolites, (E)-2,4-diene-VPA and valproyl-1-O-β acyl glucuronide (VPA-G), and their role in the hepatocyte toxicity of VPA. Currently, Dr. Chang is Professor and Associate Dean, Graduate and Postdoctoral Studies and a UBC Distinguished University Scholar. Pharmaceutical Sciences: Dr. Thomas Chang; Sauder School of Business: Dr. John Ries; Science: Dr. Mark MacLachlan; Faculty PDF Coordinators or Postdoctoral Fellows at UBC Vancouver may refer an issue to the Postdoctoral Fellows Office. Current Student - Faculty of Arts These nuclear receptors include constitutive androstane receptor (CAR) and pregnane X receptor (PXR). There are many splice variants of the human constitutive androstane receptor, several of which are expressed predominantly in the liver. The advantage of using LbDDS, such as SNEDDS, for poorly water soluble drugs is that typically the oral bioavailability is increased compared to traditional solid dosage forms. "New Investigator Award". Thus, it is important to identify chemical modulators of these receptors. Michael Smith Foundation for Health Research. 312-321, 2013. Lipid-based drug delivery systems (LbDDS) are a versatile group of formulations including self-nanoemulsifying drug delivery systems (SNEDDS). Studies are underway that focus on natural products and synthetic drugs. 1997-2001. This is either indicated in the. NNRTI therapy is associated with pharmacokinetic drug interactions, the underlying mechanisms of which are poorly understood. (Raphael Auer; Thomas Chaney; and Philip Saure) January 2018, 110: 87-102 | | | Journal of International Economics ©2018 by Elsevier. Selected Publications Wang, Shuo, Henry An, Wei-Yew Chang, Chris Gaston, and Barb Thomas (2020). Compose an error-free and grammatically correct email addressed to your specifically targeted faculty member, and remember to use their correct titles. We have collaborated with Prof. Brian R. James on the catalytic hydrogenation of lignin chromophores and bleaching of mechanical wood pulps. Of particular interest to Dr. Chang’s laboratory are nuclear receptors that govern the actions of genes (e.g. Professor Stephanie E. Chang joined UBC in January 2004 and has a joint appointment in the School of Community and Regional Planning (SCARP) and the Institute for Resources, Environment, and Sustainability (IRES). Thomas Chan. If this is your researcher profile you can log in to the Faculty & Staff portal to update your details and provide recruitment preferences. Current postdoctoral researchers Chang Lu (Aug 2018 – May 2021) Ph.D. in Strategic Management and Organization at the Alberta School of Business, University of Alberta Theoretically, he focuses on the processes by which actors instigate change in highly institutionalized contexts. Time-dependent effects of VPA on GSH depletion were characterized in relation to the effects of VPA on the WST-1, LDH, and DCF markers. ResearchGate. Email: ... Our group has extensive collaborations with researchers at UBC Chemistry. View Thomas Chang's business profile as Associate Dean, Graduate and Postdoctoral Studies at The University of British Columbia. However, the results from (E)-2-ene-VPA experiments indicated the toxic potential of in situ generated (E)-2,4-diene-VPA in sandwich-cultured rat hepatocytes, when generated at high concentrations. For halofantrine no significant increase was seen in the bioavailability for the super-SNEDDS however, for fenofibrate the AUC of the super-SNEDDS was significantly larger than for the SNEDDS.The dynamic in vitro lipolysis model is typically used in the evaluation of digestibility and solubilization capacity of SNEDDS and other LbDDS. From the reaction phenotyping experiments, CYP2C9 was the major catalyst for the formation of 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA in human liver microsomes, whereas CYP2A6 contributed partially to 3-OH-VPA formation. In order to examine the effect of lipid digestion on absorption of poorly water soluble drugs from SNEDDS the lipase inhibitor orlistat (tetrahydrolipstatin) was used. He pursued his postdoctoral studies in the Division of Cancer Pharmacology at the Dana-Farber Cancer Institute and the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. Office of the Associate Dean, Graduate and Postdoctoral Studies . Iscriviti a Facebook per connetterti con Thomas Chang e altre persone che potresti conoscere. The overall experimental strategy was to modulate the in situ formation of these two metabolites and determine the consequences on VPA toxicity in sandwich-cultured rat hepatocytes. In human subjects, the VPA-glucuronide or N-acetylcysteine metabolites were extremely weak but statistically significant predictors of lipid peroxidation in the urine of children receiving VPA. He strives to understand how social-ecological systems can be transformed to be both better and wilder. 2002. However, for super-SNEDDS precipitation seems to beinversely correlated with oral absorption when comparing the in vitro data with the in vivo data. The present thesis compared the effects of VPA, synthesized VPA metabolites, and alpha-F-VPA on markers of mitochondrial dysfunction (WST-1), cytotoxicity (LDH), oxidative stress (DCF), and glutathione (GSH) depletion in a novel model of sandwich-cultured rat hepatocytes (SCRH). hCAR-SV23, hCAR-SV24). A. G. Sanjuan and Froese, T., “ The Application of Project Management Standards and Success Factors to the Development of a Project Management Assessment Tool ”, Procedia - Social and Behavioural Sciences Journal, vol. By comparison, rilpivirine, etravirine, and efavirenz, but not nevirapine or delavirdine, were indirect activators of the wild-type isoform of CAR and inducers of cytochrome P450 2B6, a target gene of CAR. Alice Chang Project Coordinator (BeeHIVE Research Cluster) Project Manager (PCIGR) EOS South 359 (604) 822-3458. Halofantrine and fenofibrate were chosen as model drugs and for neither halofantrine nor fenofibrate digestion appeared to have an effect on the oral bioavailability in rats.The administration of halofantrine and fenofibrate in super-SNEDDS led to increasedbioavailability compared to SNEDDS when evaluated in a rat model in vivo. Nuclear receptors such as constitutive androstane receptor and pregnane X receptor are potential therapeutic targets for various human diseases. Highlight your achievements and why you are a top student. Thomas Chang è su Facebook. These data suggest that hsa-miR-18a-5p regulates PXR and contributes to drug activation of PXR. Alternatively, you may have mistakenly bookmarked the web login form instead of the actual web site you wanted to bookmark or used a link created by somebody else who made the same mistake. Urine samples from children on VPA therapy were assayed to correlate levels of VPA metabolites with the lipid peroxidation marker, 15-F2t-isoprostane. Vancouver, Canada. Networks in International Trade (Thomas Chaney) And most specially, I want to give my deep gratitude to the long-serving co-managing directors, Joyce Hinton and Cameron McGill, and several other staff members as well, who have been here since the beginning. Rilpivirine and rifampin did not affect PXR expression, but it decreased endogenous expression of hsa-miR-18a-5p in LS180 cells.

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