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. 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. He strives to understand how social-ecological systems can be transformed to be both better and wilder. Position Title: Adjunct Professor. The relationships between the various pathophysiological findings of VPA-induced hepatotoxicity and the role of VPA biotransformation in the induction of hepatotoxicity have not been systematically investigated. Credits that have an established equivalent between campuses can be used to satisfy course-specific degree requirements. Among the NNRTIs investigated, only efavirenz activated the SV23 and SV24 splice variants of CAR, indicating that NNRTIs activated CAR in a drug-specific and isoform-selective manner. Reporter gene assays revealed a functional hsa-miR-18a-5p microRNA recognition element in the 3′-untranslated region of PXR. 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. Canadian Institute of Health Research and Rx&D Health Research Foundation. 2007-2012. Urine samples from children on VPA therapy were assayed to correlate levels of VPA metabolites with the lipid peroxidation marker, 15-F2t-isoprostane. To further understand PXR regulation by rilpivirine, the role of microRNA in rilpivirine activation of PXR was investigated. Alice coordinates research activities, events and meetings for BeeHIVE, a UBC-based research excellence cluster. Cane Kong has uploaded 2266 photos to Flickr. G+PS regularly provides virtual sessions that focus on admission requirements and procedures and tips how to improve your application. 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. "New Investigator Award". Address the faculty members by name. We have collaborated with Prof. Brian R. James on the catalytic hydrogenation of lignin chromophores and bleaching of mechanical wood pulps. 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. 2006. Rilpivirine, etravirine, and efavirenz, but not nevirapine or delavirdine, were identified as agonists of PXR and inducers of cytochrome P450 3A4 (CYP3A4), a target gene of PXR. Convey the specific ways the program/lab/faculty member is a good fit for the research you are interested in/already conducting. Liquidity Constrained Exporters (Thomas Chaney) November 2016, 72: 141-54 | | Journal of Economic Dynamics and Control ©2016 by Elsevier. In summary, CYP1B1, CYP2A1, CYP17A1, mEH and POR were detected in rat testis and their expression was confined to interstitial cells (CYP1B1, CYP2A1, CYP17A1, mEH and POR) and seminiferous tubules (mEH and POR). Thomas Hu. Thomas Chang è su Facebook. 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. The contribution of the CYP- and UGT-mediated biotransformation of VPA in VPA-induced toxicity was also examined. hCAR-SV23, hCAR-SV24). Iscriviti a Facebook per connetterti con Thomas Chang e altre persone che potresti conoscere. Of particular interest to Dr. Chang’s laboratory are nuclear receptors that govern the actions of genes (e.g. steroid hormones, vitamins, bile acids). Overall, the results of the present study add value to the existing knowledge on the role of reactive metabolites of VPA in VPA hepatotoxicity. The effects of glutathione supplementation on the attenuation of the markers for VPA-induced toxicities were investigated. transporters such as P-glycoprotein and drug-metabolizing enzymes such as cytochromes P450), and regulate the transport, bioactivation and detoxification of xenobiotics (e.g. Suppression or induction of these enzymes in testis may alter the magnitude of tissue exposure to xenobiotics and endobiotics levels. For some programs this is an essential step while others match successful applicants with faculty members within the first year of study. 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. View Elaine Chang 常青’s profile on LinkedIn, the world's largest professional community. Find contact's direct phone number, email address, work history, and more. K. J. Elwood, “ Performance of Concrete Buildings in the 22 February 2011 Christchurch Earthquake and Implications for Canadian Codes ”, Canadian Journal of Civil Engineering, 2013.. Google Scholar; BibTex The Changeling by Thomas Middleton and William Rowley Directed by MFA Director Luciana Silvestre Fernandes. Chang TKH. 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. These nuclear receptors include constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Clinical use of VPA is associated with a rare, but possibly fatal, idiosyncratic hepatotoxicity. 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. Chang TKH. 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. The mechanism of VPA hepatotoxicity is not known, but it may involve reactive metabolites of VPA. The University of British Columbia. 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. Include a brief outline of your academic background, why you are interested in working with the faculty member, and what experience you could bring to the department. Chang TKH. 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. 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. 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. The experimental approaches included cell-based luciferase reporter gene assays, in vitro competitive ligand binding assay, nuclear translocation analysis by confocal imaging, coactivator recruitment assays, and target gene expression determination in primary human hepatocytes. 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. "Senior Scholar Award". "Distinguished University Scholar Award". This means credits from a different campus will not be converted to transfer credit but may have a course equivalency. Nuclear receptors are evolutionarily-related DNA-binding transcription factors that regulate the expression of a broad array of genes involved in various biological processes. 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. 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. staff. Studies are underway that focus on natural products and synthetic drugs. Stephanie E. Chang is a UBC professor with a joint appointment in the School of Community and Regional Planning and the Institute for Resources, Environment, and Sustainability. Thomas Chan. 1997-2002. BeeHIVE PCIGR. drugs, environmental chemicals) and endogenous substances (e.g. Dr. Thomas K. H. Chang completed a bachelor of science and a doctor of philosophy in pharmaceutical sciences at 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. Chang TKH. Ensure to craft compelling answers to these questions. In the present study, constitutive expression of various xenobiotic-metabolizing enzymes (Study 1) and their regulation by 17β-estradiol benzoate (EB) (Study 2) and an endocrine disrupting chemical, bisphenol A (BPA) (Study 3), were investigated in adult rat testis. Burroughs Wellcome Fund (U.S.A.). In Study 2, subcutaneous (sc) treatment of EB at 0.004, 0.04, 0.4 or 4 μmol/kg once daily for 14 days suppressed testicular expression of CYP1B1, CYP2A1 and CYP17A1 at each of the dosages tested. People & Change: Thomas Veal October 24, 2019. 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. If this is your researcher profile you can log in to the Faculty & Staff portal to update your details and provide recruitment preferences. Thomas Ming Swi Chang, OC (born 8 April 1933) is a Canadian physician, medical scientist, and inventor.. Thomas SchneiderProfessor of Egyptology and Near Eastern Studiesthomas.schneider@ubc.cawork phone: 604-827-4316 Vancouver, Canada. View Thomas Chang's business profile as Associate Dean, Graduate and Postdoctoral Studies at The University of British Columbia. Networks in International Trade (Thomas Chaney) Thomas Chang (UBC Professor): Pharmacology, Nuclear Receptor, Drug-Metabolizing Enzymes, Cytochrome P450, Gene Expression, Gene regulation ResearchGate. Story submitted by. Elaine has 6 jobs listed on their profile. CORONAVIRUS (COVID-19): please review UBC’s general information and FAQs and G+PS's graduate student-specific information. There are 48 known members in the superfamily of nuclear receptors in the human genome. thomas.chang@ubc.ca. However, for super-SNEDDS precipitation seems to beinversely correlated with oral absorption when comparing the in vitro data with the in vivo data. 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. 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. Various studies are ongoing to investigate the functionality of naturally occurring splice variants of the human constitutive androstane receptor (e.g. (Raphael Auer; Thomas Chaney; and Philip Saure) January 2018, 110: 87-102 | | | Journal of International Economics ©2018 by Elsevier. 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. Chang TKH. 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. Chang TKH. 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. I am a software engineer at Google Brain, based in Toronto, Canada. 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. Compose an error-free and grammatically correct email addressed to your specifically targeted faculty member, and remember to use their correct titles. Currently, Dr. Chang is Professor and Associate Dean, Graduate and Postdoctoral Studies and a UBC Distinguished University Scholar. 1998. 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. In Study 3, administration of BPA at 400, 800 or 1600 μmol/kg sc once daily for 14 days decreased testicular CYP1B1, CYP2A1, CYP17A1, mEH and POR protein expression at each of the dosages tested. She held a Canada Research Chair (Tier 2) in Disaster Management and Urban Sustainability from 2004 to 2013. Rilpivirine and rifampin did not affect PXR expression, but it decreased endogenous expression of hsa-miR-18a-5p in LS180 cells. 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. Prior to that, I was a machine learning researcher at Borealis AI. I finished my Ph.D. in statistics at the University of British Columbia. Stephanie Chang (UBC Professor): natural disasters, risk, resilience, climate change adaptation, infrastructure systems, earthquakes, coastal hazards This is either indicated in the. Email: ... Our group has extensive collaborations with researchers at UBC Chemistry. "Killam Faculty Research Fellowship". Functional Analysis of Splice Variants of Nuclear Receptors. Office of the Associate Dean, Graduate and Postdoctoral Studies . Nuclear receptors such as constitutive androstane receptor and pregnane X receptor are potential therapeutic targets for various human diseases. As part of this study, a sensitive and rapid ultra-high performance liquid chromatography – tandem mass spectrometry method for the quantification of VPA-G in hepatocyte culture medium was developed, validated, and applied successfully to quantify in situ concentrations of VPA-G. From a comprehensive screening of several known inducers of uridine 5'-diphospho-glucuronosyltransferase enzymes, this study identified β-naphthoflavone, L-sulforaphane, and phenobarbital to be effective in increasing the in situ formation of VPA-G from VPA in sandwich-cultured rat hepatocytes. Do not send non-specific, mass emails to everyone in the department hoping for a match. Lastly, the contributions of hepatic CYP-enzymes in the oxidative metabolism of VPA were characterized in human liver microsomes. She held a Canada Research Chair (Tier 2) in Disaster Management and Urban Sustainability from 2004 to 2013. Explore Cane Kong's photos on Flickr. 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. View the profiles of people named Thomas Chang. The present study investigated the effects of NNRTIs on the activity of pregnane X receptor (PXR) and constitutive androstane receptor (CAR), key transcriptional factors regulating the expression of various drug-metabolizing enzymes and transporters. 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. 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). Current Student - Faculty of Arts This will pave the way for future drug development efforts to find selective, potent and effective modulators. Be certain that their research is indeed what you are hoping to study. Join Facebook to connect with Thomas Chang and others you may know. Bioinformatic analysis (www.microRNA.org) predicted sequence complementarity between hsa-miR-18a-5p and PXR. To rebook or refund preview tickets, please contact box.office@ubc… Lipid-based drug delivery systems (LbDDS) are a versatile group of formulations including self-nanoemulsifying drug delivery systems (SNEDDS). Dr. Chang also completed the faculty certificate program on Teaching and Learning in Higher Education at UBC. 2002. Identify specific faculty members who are conducting research in your specific area of interest. 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. Chemical inhibition experiments indicated that the CYP- and UGT-mediated metabolism of VPA or the in situ generated VPA metabolites were unlikely involved in the observed VPA-induced toxicities in SCRH. (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. Experience. Office Phone Number: 604-225-5836. 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. Kai is an interdisciplinary, problem-oriented sustainability scientist, trained in ecology, policy, and ethics from Princeton and Stanford Universities. 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). "Research Career Award". Michael Smith Foundation for Health Research. The splice variants may have different regulation, function and tissue distribution when compared with the wild-type isoform. Thomas Chang & Co is a law firm located in Chinatown, Sydney with attorneys, conveyancers and Chinese solicitors acting as migration agent dealing with … (604) 822-7795 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. Highlight your achievements and why you are a top student. 312-321, 2013. Alice Chang Project Coordinator (BeeHIVE Research Cluster) Project Manager (PCIGR) EOS South 359 (604) 822-3458. 74, pp. GSH may serve a protective role against VPA-induced oxidative stress in SCRH. Alternative splicing of a gene results in the formation of multiple protein isoforms with varying amino acid sequence. Currently an Assistant Professor at the UBC Institute for the Oceans and Fisheries, Tom works on quantitative solutions to critical fishery management problems. WEATHER ADVISORY! Future studies should investigate the role of VPA-CoA thioester formation on VPA toxicity in sandwich-cultured rat hepatocytes.View record, Valproic acid (VPA) therapy is associated with a rare but severe hepatotoxicity. 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. Consistent with this finding, alpha-F-VPA, which is resistant to bioactivation by several biotransformation pathways, was nontoxic. British Columbia Health Research Foundation. Your contact should be genuine rather than generic. 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. "Research Scholar Award". Dr. Thomas K. H. Chang completed a bachelor of science and a doctor of philosophy in pharmaceutical sciences at UBC. Google Scholar; BibTex Familiarize yourself with their work, read their recent publications and past theses/dissertations that they supervised. 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. The overall goal of Dr. Chang’s research program is to enhance our understanding of the molecular and cellular determinants that regulate the transport, bioactivation and detoxification of drugs, and how they affect inter-individual differences in drug action. The University of British Columbia is a global centre for research and teaching, consistently ranked among the top 20 public universities in the world. EB also suppressed mEH and POR protein expression at dosages > 0.04 μmol/kg. In contrast, over-expression of hsa-miR-18a-5p decreased PXR mRNA expression and CYP3A4 inducibility by rilpivirine and rifampin. NNRTI therapy is associated with pharmacokinetic drug interactions, the underlying mechanisms of which are poorly understood. UBC courses are eligible for credit towards a UBC degree program on either campus. Chemical Biology and Pharmacology of Nuclear Receptors. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are important anti-retroviral drugs indicated in combination therapy of human immunodeficiency virus-1 (HIV-1) infection. Demonstrate that you are familiar with their research: Convey the specific ways you are a good fit for the program. The supervision enquiry form guides you with targeted questions. These data suggest that hsa-miR-18a-5p regulates PXR and contributes to drug activation of PXR. The role of the allowable cut effect on the benefits of adopting genomic technology in the Alberta forest sector Canadian Journal of Agricultural Economics/Revue canadienne d'agroeconomie W-Y Chang, C Gaston, J Cool, and B Thomas (2019). 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