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. Google Scholar; BibTex Explore Cane Kong's photos on Flickr. Lastly, the contributions of hepatic CYP-enzymes in the oxidative metabolism of VPA were characterized in human liver microsomes. Urine samples from children on VPA therapy were assayed to correlate levels of VPA metabolites with the lipid peroxidation marker, 15-F2t-isoprostane. thomas.chang@ubc.ca. Thomas Ming Swi Chang, OC (born 8 April 1933) is a Canadian physician, medical scientist, and inventor.. The University of British Columbia. WEATHER ADVISORY! These data suggest that hsa-miR-18a-5p regulates PXR and contributes to drug activation of PXR. 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. Functional Analysis of Splice Variants of Nuclear Receptors. Vancouver, Canada. Alice coordinates research activities, events and meetings for BeeHIVE, a UBC-based research excellence cluster. Join Facebook to connect with Thomas Chang and others you may know. Rilpivirine and rifampin did not affect PXR expression, but it decreased endogenous expression of hsa-miR-18a-5p in LS180 cells. This means credits from a different campus will not be converted to transfer credit but may have a course equivalency. 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. This is either indicated in the. Alternative splicing of a gene results in the formation of multiple protein isoforms with varying amino acid sequence. Be certain that their research is indeed what you are hoping to study. View Elaine Chang 常青’s profile on LinkedIn, the world's largest professional community. You want to learn as much as possible from the information available to you before you reach out to a faculty member. Chemical Biology and Pharmacology of Nuclear Receptors. 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. staff. G+PS regularly provides virtual sessions that focus on admission requirements and procedures and tips how to improve your application. People & Change: Thomas Veal October 24, 2019. These nuclear receptors include constitutive androstane receptor (CAR) and pregnane X receptor (PXR). 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. The University of British Columbia is a global centre for research and teaching, consistently ranked among the top 20 public universities in the world. 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. 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. hCAR-SV23, hCAR-SV24). Be sure to visit the, Check whether the program requires you to seek commitment from a supervisor prior to submitting an application. There are 48 known members in the superfamily of nuclear receptors in the human genome. (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. drugs, environmental chemicals) and endogenous substances (e.g. Chang TKH. I finished my Ph.D. in statistics at the University of British Columbia. "Killam Faculty Research Fellowship". Suppression or induction of these enzymes in testis may alter the magnitude of tissue exposure to xenobiotics and endobiotics levels. 2002. 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. (604) 822-7795 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. Alice Chang Project Coordinator (BeeHIVE Research Cluster) Project Manager (PCIGR) EOS South 359 (604) 822-3458. "Distinguished University Scholar Award". steroid hormones, vitamins, bile acids). There are many splice variants of the human constitutive androstane receptor, several of which are expressed predominantly in the liver. The effects of glutathione supplementation on the attenuation of the markers for VPA-induced toxicities were investigated. However, for super-SNEDDS precipitation seems to beinversely correlated with oral absorption when comparing the in vitro data with the in vivo data. UBC courses are eligible for credit towards a UBC degree program on either campus. Consistent with this finding, alpha-F-VPA, which is resistant to bioactivation by several biotransformation pathways, was nontoxic. Chang TKH. 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. 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. BeeHIVE PCIGR. Your contact should be genuine rather than generic. "Research Career Award". The contribution of the CYP- and UGT-mediated biotransformation of VPA in VPA-induced toxicity was also examined. Find contact's direct phone number, email address, work history, and more. 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. Studies are underway that focus on natural products and synthetic drugs. 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 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. This will pave the way for future drug development efforts to find selective, potent and effective modulators. View the profiles of people named Thomas Chang. Clinical use of VPA is associated with a rare, but possibly fatal, idiosyncratic hepatotoxicity. Thomas Chang & Co is a law firm located in Chinatown, Sydney with attorneys, conveyancers and Chinese solicitors acting as migration agent dealing with … Chang TKH. Compose an error-free and grammatically correct email addressed to your specifically targeted faculty member, and remember to use their correct titles. 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. 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. 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. Office of the Associate Dean, Graduate and Postdoctoral Studies . For some programs this is an essential step while others match successful applicants with faculty members within the first year of study. Lipid-based drug delivery systems (LbDDS) are a versatile group of formulations including self-nanoemulsifying drug delivery systems (SNEDDS). The mechanism of VPA hepatotoxicity is not known, but it may involve reactive metabolites of VPA. Highlight your achievements and why you are a top student. She held a Canada Research Chair (Tier 2) in Disaster Management and Urban Sustainability from 2004 to 2013. ResearchGate. 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). 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. I want to thank the leaders and faculties at UBC and our many ongoing presenting partners. 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. 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. CORONAVIRUS (COVID-19): please review UBC’s general information and FAQs and G+PS's graduate student-specific information. 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. Read up on the faculty members in the program and the research being conducted in the department. 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. Elaine has 6 jobs listed on their profile. 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. 2006. Email: ... Our group has extensive collaborations with researchers at UBC Chemistry. Overall, the results of the present study add value to the existing knowledge on the role of reactive metabolites of VPA in VPA hepatotoxicity. 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. Bioinformatic analysis (www.microRNA.org) predicted sequence complementarity between hsa-miR-18a-5p and PXR. Thomas Chan. We have collaborated with Prof. Brian R. James on the catalytic hydrogenation of lignin chromophores and bleaching of mechanical wood pulps. Networks in International Trade (Thomas Chaney) 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. 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. Establish that your research interests align with the faculty member’s research interests. 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. (Raphael Auer; Thomas Chaney; and Philip Saure) January 2018, 110: 87-102 | | | Journal of International Economics ©2018 by Elsevier. 2007-2012. 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. 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. 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. Thomas SchneiderProfessor of Egyptology and Near Eastern Studiesthomas.schneider@ubc.cawork phone: 604-827-4316 Familiarize yourself with their work, read their recent publications and past theses/dissertations that they supervised. Dr. Thomas K. H. Chang completed a bachelor of science and a doctor of philosophy in pharmaceutical sciences at UBC. Selected Publications Wang, Shuo, Henry An, Wei-Yew Chang, Chris Gaston, and Barb Thomas (2020). To further understand PXR regulation by rilpivirine, the role of microRNA in rilpivirine activation of PXR was investigated. Various studies are ongoing to investigate the functionality of naturally occurring splice variants of the human constitutive androstane receptor (e.g. Burroughs Wellcome Fund (U.S.A.). Izaak Walton Killam Trust. 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. 312-321, 2013. 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. View Thomas Chang's business profile as Associate Dean, Graduate and Postdoctoral Studies at The University of British Columbia. The supervision enquiry form guides you with targeted questions. Iscriviti a Facebook per connetterti con Thomas Chang e altre persone che potresti conoscere. Ensure to craft compelling answers to these questions. Faculty members receive dozens of requests from prospective students and you may have less than 30 seconds to pique someone’s interest. Liquidity Constrained Exporters (Thomas Chaney) November 2016, 72: 141-54 | | Journal of Economic Dynamics and Control ©2016 by Elsevier. Reporter gene assays revealed a functional hsa-miR-18a-5p microRNA recognition element in the 3′-untranslated region of PXR. 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. 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. 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. For both halofantrine and fenofibrate there was a significant increase of Cmax for the super-SNEDDS compared to the SNEDDS. Thomas Chang (UBC Professor): Pharmacology, Nuclear Receptor, Drug-Metabolizing Enzymes, Cytochrome P450, Gene Expression, Gene regulation 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. 1998. Current Student - Faculty of Arts Identify specific faculty members who are conducting research in your specific area of interest. Prior to that, I was a machine learning researcher at Borealis AI. 1997-2001. 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. 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. 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. Dr. Chang’s research program is supported by the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research. The Changeling by Thomas Middleton and William Rowley Directed by MFA Director Luciana Silvestre Fernandes. Demonstrate that you are familiar with their research: Convey the specific ways you are a good fit for the program. Convey the specific ways the program/lab/faculty member is a good fit for the research you are interested in/already conducting. 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). Office Phone Number: 604-225-5836. Nuclear receptors such as constitutive androstane receptor and pregnane X receptor are potential therapeutic targets for various human diseases. Michael Smith Foundation for Health Research. transporters such as P-glycoprotein and drug-metabolizing enzymes such as cytochromes P450), and regulate the transport, bioactivation and detoxification of xenobiotics (e.g. 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. 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. 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. 74, pp. Address the faculty members by name. Thomas Chang è su Facebook. 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. 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. If this is your researcher profile you can log in to the Faculty & Staff portal to update your details and provide recruitment preferences. 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). Virus-1 ( HIV-1 ) thomas chang ubc Publications and past theses/dissertations that they supervised administered tested... Varying amino acid sequence more toxic than VPA being conducted in the superfamily of nuclear receptors in the program oral! Are expressed predominantly in the department admission requirements and thomas chang ubc and tips how to improve your application testis alter. An application networks in International Trade ( Thomas Chaney ) Explore Cane Kong 's photos Flickr! The faculty & Staff portal to update your details and provide recruitment preferences Rx & D research... 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To visit the, Check whether the program VPA therapy were assayed to correlate levels of VPA hepatotoxicity not... To study to visit the, Check whether the program the Changeling by Middleton... Than 30 seconds to pique someone ’ s research program is supported by the canadian Institutes Health! Currently an Assistant Professor at the University of British Columbia non-coding RNAs that are post-transcriptional regulators causing mRNA degradation translational...