- Overview
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In all organisms, DNA is the matter of inheritance. As such, DNA provides the blueprint to build and operate each individual organism. Decoding the information contained in the DNA is thus a key process, termed ‘transcription’. Transcription needs to happen at the right time and in the right place, and deregulated transcription causes diseases such as cancers, diabetes, and developmental abnormalities. But how does a creature transcribe the specific DNA programs to develop a normal, functioning organ, or to adapt its life-style to a specific external influence?
My lab studies the so-called ‘Mediator’, a molecular machine that is required for transcription: without it, the information contained in DNA cannot be properly decoded. Intriguingly, several Mediator subunits are mutated in human diseases, including certain cancers and neurodevelopmental disorders, but how and why the Mediator mutations cause disease remains poorly understood.
Our mission is to define why and how Mediator function assures normal development, prevents sickness, and promotes healthy aging. We use the worm Caenorhabditis elegans and the house mouse as experimental animal models, because they share certain aspects of human biology, and because we can control their genetics. With this approach we dissect how individual Mediator subunits regulate lipid metabolism and fat storage, detoxification programs, organ development and differentiation pathways, and aging. By providing new insights into how DNA is transcribed, our investigations may lead to new diagnostics and/or therapeutics that can help cure human diseases.
- Publications
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The unfolded protein response of the endoplasmic reticulum protects Caenorhabditis elegans against DNA damage caused by stalled replication forks
G3: Genes, Genomes, Genetics
Jiaming Xu and Brendil Sabatino and Junran Yan and Glafira Ermakova and Kelsie R S Doering and Stefan Taubert
DOI: 10.1093/g3journal/jkae017
04/2024Mediator subunit MDT-15 promotes expression of propionic acid breakdown genes to prevent embryonic lethality in Caenorhabditis elegans
G3: Genes, Genomes, Genetics
Grace Ying Shyen Goh and Arshia Beigi and Junran Yan and Kelsie R S Doering and Stefan Taubert
DOI: 10.1093/g3journal/jkad087
06/2023Methods to extract and study the biological effects of murine gut microbiota using Caenorhabditis elegans as a screening host
PLOS ONE
Claudia Miriam Alonzo-De la Rosa and Stéphanie Miard and Stefan Taubert and Frédéric Picard
DOI: 10.1371/journal.pone.0281887
02/2023The unfolded protein response of the endoplasmic reticulum protectsCaenorhabditis elegansagainst DNA damage caused by stalled replication forks
Jiaming Xu and Brendil Sabatino and Stefan Taubert
DOI: 10.1101/2023.02.23.529758
02/2023Nuclear hormone receptor NHR-49 is an essential regulator of stress resilience and healthy aging in Caenorhabditis elegans
Frontiers in Physiology
DOI: 10.3389/fphys.2023.1241591
2023Mediator subunit MDT-15 promotes expression of propionic acid breakdown genes to prevent embryonic lethality inCaenorhabditis elegans
Grace Ying Shyen Goh and Arshia Beigi and Junran Yan and Kelsie R. S. Doering and Stefan Taubert
DOI: 10.1101/2022.12.16.520805
12/2022cSurvival: a web resource for biomarker interactions in cancer outcomes and in cell lines
Briefings in Bioinformatics
Xuanjin Cheng and Yongxing Liu and Jiahe Wang and Yujie Chen and Andrew Gordon Robertson and Xuekui Zhang and Steven J M Jones and Stefan Taubert
DOI: 10.1093/bib/bbac090
05/2022Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans
eLife
Kelsie RS Doering and Xuanjin Cheng and Luke Milburn and Ramesh Ratnappan and Arjumand Ghazi and Dana L Miller and Stefan Taubert
DOI: 10.7554/eLife.67911
03/2022cSurvival: a web resource for biomarker interactions in cancer outcomes
Xuanjin Cheng and Yongxing Liu and Jiahe Wang and Yujie Chen and A. Gordon Robertson and Xuekui Zhang and Steven J. M. Jones and Stefan Taubert
DOI: 10.1101/2021.11.15.468756
11/2021eVITTA: a web-based visualization and inference toolbox for transcriptome analysis
Nucleic Acids Research
Xuanjin Cheng and Junran Yan and Yongxing Liu and Jiahe Wang and Stefan Taubert
DOI: 10.1093/nar/gkab366
07/2021NHR-49/PPAR-a and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase
eLife
Khursheed A Wani and Debanjan Goswamy and Stefan Taubert and Ramesh Ratnappan and Arjumand Ghazi and Javier E Irazoqui
DOI: 10.7554/eLife.62775
05/2021Nuclear Hormone Receptor NHR-49 controls a HIF-1-independent hypoxia adaptation pathway in Caenorhabditis elegans
Kelsie R. S. Doering and Xuanjin Cheng and Luke Milburn and Ramesh Ratnappan and Arjumand Ghazi and Dana L. Miller and Stefan Taubert
DOI: 10.1101/2021.02.24.432575
02/2021Beyond Proteostasis: Lipid Metabolism as a New Player in ER Homeostasis
Metabolites
Jiaming Xu and Stefan Taubert
DOI: 10.3390/metabo11010052
01/2021Xenobiotic metabolism and transport in Caenorhabditis elegans
Journal of Toxicology and Environmental Health - Part B: Critical Reviews
Hartman, J.H. and Widmayer, S.J. and Bergemann, C.M. and King, D.E. and Morton, K.S. and Romersi, R.F. and Jameson, L.E. and Leung, M.C.K. and Andersen, E.C. and Taubert, S. and Meyer, J.N.
DOI: 10.1080/10937404.2021.1884921
2021NHR-49/PPAR-a and HLH-30/TFEB promote C. elegans host defense via a flavin-containing monooxygenase
Khursheed A. Wani and Debanjan Goswamy and Stefan Taubert and Ramesh Ratnappan and Arjumand Ghazi and Javier E. Irazoqui
DOI: 10.1101/2020.09.03.282087
09/2020Stress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stress
Journal of Cell Biology
Nurulain Ho and Wei Sheng Yap and Jiaming Xu and Haoxi Wu and Jhee Hong Koh and Wilson Wen Bin Goh and Bhawana George and Shu Chen Chong and Stefan Taubert and Guillaume Thibault
DOI: 10.1083/jcb.201909165
07/2020Stress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stress
Journal of Cell Biology
Ho, N. and Yap, W.S. and Xu, J. and Wu, H. and Koh, J.H. and Goh, W.W.B. and George, B. and Chong, S.C. and Taubert, S. and Thibault, G.
DOI: 10.1083/JCB.201909165
2020ER stress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stress
Nurulain Ho and Haoxi Wu and Jiaming Xu and Jhee Hong Koh and Wei Sheng Yap and Wilson Wen Bin Goh and Shu Chen Chong and Stefan Taubert and Guillaume Thibault
DOI: 10.1101/774133
09/2019Epigenetic regulator G9a provides glucose as a sweet key to stress resistance
PLOS Biology
Kelsie R. S. Doering and Stefan Taubert
DOI: 10.1371/journal.pbio.3000236
04/2019Mediator subunit MDT-15/MED15 and Nuclear Receptor HIZR-1/HNF4 cooperate to regulate toxic metal stress responses in Caenorhabditis elegans
Shomer N and Kadhim AZ and Grants JM and Cheng X and Poon AF and Lee MYY and Bhanshali F and Muhuri A and Park JI and Lee D and Lee SV and Lynn FC and Taubert S
DOI: 10.1101/565739
03/2019Mediator subunit MDT-15/MED15 and Nuclear Receptor HIZR-1/HNF4 cooperate to regulate toxic metal stress responses in Caenorhabditis elegans
PLoS Genetics
Shomer, N. and Zacharie Kadhim, A. and Margaret Grants, J. and Cheng, X. and Alhusari, D. and Bhanshali, F. and Poon, A.F.-Y. and Ya Lee, M.Y. and Muhuri, A. and In Park, J. and Shih, J. and Lee, D. and Lee, S.-J.V. and Lynn, F.C. and Taubert, S.
DOI: 10.1371/journal.pgen.1008508
2019MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis
PLoS Biology
Lee, D. and An, S.W.A. and Jung, Y. and Yamaoka, Y. and Ryu, Y. and Goh, G.Y.S. and Beigi, A. and Yang, J.-S. and Jung, G.Y. and Ma, D.K. and Ha, C.M. and Taubert, S. and Lee, Y. and Lee, S.-J.V.
DOI: 10.1371/journal.pbio.3000415
2019Activity of translation regulator eukaryotic elongation factor-2 kinase is increased in Parkinson disease brain and its inhibition reduces alpha synuclein toxicity
Acta Neuropathologica Communications
DOI: 10.1186/s40478-018-0554-9
PubMed: 29961428
07/2018C. elegans Mediator 15 permits low temperature-induced longevity via regulation of lipid and protein homeostasis
Lee D and An SWA and Jung Y and Yamaoka Y and Ryu Y and Goh GYS and Beigi A and Ma D and Ha CM and Taubert S and Lee Y and Lee SV
DOI: 10.1101/366153
07/2018NHR-49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting
Aging Cell
Grace Y. S. Goh and Johnathan J. Winter and Forum Bhanshali and Kelsie R. S. Doering and Regina Lai and Kayoung Lee and Elizabeth A. Veal and Stefan Taubert
DOI: 10.1111/acel.12743
06/2018The R148.3 Gene Modulates Caenorhabditis elegans Lifespan and Fat Metabolism
G3: Genes|Genomes|Genetics
Catherine Roy-Bellavance and Jennifer M. Grants and Stéphanie Miard and Kayoung Lee and Évelyne Rondeau and Chantal Guillemette and Martin J. Simard and Stefan Taubert and Frédéric Picard
DOI: 10.1534/g3.117.041681
06/2017Genomic and Cytogenetic Characterization of a Balanced Translocation Disrupting NUP98
Cytogenetic and Genome Research
My Linh Thibodeau and Michelle Steinraths and Lindsay Brown and Zheyuan Zong and Naomi Shomer and Stefan Taubert and Karen L. Mungall and Yussanne P. Ma and Rosemary Mueller and Inanc Birol and Anna Lehman
DOI: 10.1159/000479463
2017eEF2K inhibition blocks Aß42 neurotoxicity by promoting an NRF2 antioxidant response
Acta Neuropathologica
Jan, A. and Jansonius, B. and Delaidelli, A. and Somasekharan, S.P. and Bhanshali, F. and Vandal, M. and Negri, G.L. and Moerman, D. and MacKenzie, I. and Calon, F. and Hayden, M.R. and Taubert, S. and Sorensen, P.H.
DOI: 10.1007/s00401-016-1634-1
2017Gain-of-Function Alleles in Caenorhabditis elegans Nuclear Hormone Receptor nhr-49 Are Functionally Distinct
PLOS ONE
Kayoung Lee and Grace Ying Shyen Goh and Marcus Andrew Wong and Tara Leah Klassen and Stefan Taubert
DOI: 10.1371/journal.pone.0162708
09/2016Caenorhabditis elegans Gets Metabolic Network Models
Cell Systems
Stefan Taubert
DOI: 10.1016/j.cels.2016.05.003
05/2016Bacterial diet affects vulval organogenesis in Caenorhabditis elegans Mediator kinase module mutants
Matters
DOI: 10.19185/matters.201605000012
05/2016The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans
Genetics
Jennifer M. Grants and Lisa T. L. Ying and Akinori Yoda and Charlotte C. You and Hideyuki Okano and Hitoshi Sawa and Stefan Taubert
DOI: 10.1534/genetics.115.180265
02/2016s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways
Cell Metabolism
Wei Ding and Lorissa J. Smulan and Nicole S. Hou and Stefan Taubert and Jennifer L. Watts and Amy K. Walker
DOI: 10.1016/j.cmet.2015.07.013
10/2015The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator
Nucleic Acids Research
Jennifer M. Grants and Grace Y. S. Goh and Stefan Taubert
DOI: 10.1093/nar/gkv037
02/2015Membrane lipids and the endoplasmic reticulum unfolded protein response: An interesting relationship
Worm
Nicole S Hou and Stefan Taubert
DOI: 10.4161/21624046.2014.962405
09/2014Activation of the endoplasmic reticulum unfolded protein response by lipid disequilibrium without disturbed proteostasis in vivo
Proceedings of the National Academy of Sciences
N. S. Hou and A. Gutschmidt and D. Y. Choi and K. Pather and X. Shi and J. L. Watts and T. Hoppe and S. Taubert
DOI: 10.1073/pnas.1318262111
05/2014The conserved Mediator subunit MDT-15 is required for oxidative stress responses in Caenorhabditis elegans
Aging Cell
Goh, G.Y.S. and Martelli, K.L. and Parhar, K.S. and Kwong, A.W.L. and Wong, M.A. and Mah, A. and Hou, N.S. and Taubert, S.
DOI: 10.1111/acel.12154
2014The C. elegans CDK8 Mediator module regulates axon guidance decisions in the ventral nerve cord and during dorsal axon navigation
Developmental Biology
Andreas Steimel and Jinkyo Suh and Angela Hussainkhel and Samineh Deheshi and Jennifer M. Grants and Richard Zapf and Donald G. Moerman and Stefan Taubert and Harald Hutter
DOI: 10.1016/j.ydbio.2013.02.009
05/2013Coordinate Regulation of Lipid Metabolism by Novel Nuclear Receptor Partnerships
PLoS Genetics
Pranali P. Pathare and Alex Lin and Karin E. Bornfeldt and Stefan Taubert and Marc R. Van Gilst
DOI: 10.1371/journal.pgen.1002645
04/2012Repression of a Potassium Channel by Nuclear Hormone Receptor and TGF-ß Signaling Modulates Insulin Signaling in Caenorhabditis elegans
PLoS Genetics
Donha Park and Karen L. Jones and Hyojin Lee and Terrance P. Snutch and Stefan Taubert and Donald L. Riddle
DOI: 10.1371/journal.pgen.1002519
02/2012Function and Regulation of Lipid Biology in Caenorhabditis elegans Aging
Frontiers in Physiology
Nicole Shangming Hou and Stefan Taubert
DOI: 10.3389/fphys.2012.00143
2012Somatic differentiation and MR imaging of magnetically labeled human embryonic stem cells.
Cell transplantation
Nejadnik, H. and Henning, T.D. and Castaneda, R.T. and Boddington, S. and Taubert, S. and Jha, P. and Tavri, S. and Golovko, D. and Ackerman, L. and Meier, R. and Daldrup-Link, H.E.
DOI: 10.3727/096368912X653156
2012Somatic Differentiation and MR Imaging of Magnetically Labeled Human Embryonic Stem Cells
Cell Transplantation
Hossein Nejadnik and Tobias D. Henning and Rosalinda T. Castaneda and Sophie Boddington and Stefan Taubert and Priyanka Jha and Sidhartha Tavri and Daniel Golovko and Larry Ackerman and Reinhard Meier and Heike E. Daldrup-Link
DOI: 10.3727/096368912x653156
2012Nuclear hormone receptors in nematodes: Evolution and function
Molecular and Cellular Endocrinology
Stefan Taubert and Jordan D. Ward and Keith R. Yamamoto
DOI: 10.1016/j.mce.2010.04.021
03/2011SET(BP1)-ing the stage for a better understanding of Schinzel-Giedion syndrome
Clinical Genetics
S Taubert
DOI: 10.1111/j.1399-0004.2010.01505.x
09/2010Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network
Molecular Systems Biology
H Efsun Arda and Stefan Taubert and Lesley T MacNeil and Colin C Conine and Ben Tsuda and Marc Van Gilst and Reynaldo Sequerra and Lynn Doucette-Stamm and Keith R Yamamoto and Albertha J M Walhout
DOI: 10.1038/msb.2010.23
05/2010The Mediator Subunit MDT-15 Confers Metabolic Adaptation to Ingested Material
PLoS Genetics
Stefan Taubert and Malene Hansen and Marc R. Van Gilst and Samantha B. Cooper and Keith R. Yamamoto
DOI: 10.1371/journal.pgen.1000021
02/2008Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans
Aging Cell
Malene Hansen and Stefan Taubert and Douglas Crawford and Nataliya Libina and Seung-Jae Lee and Cynthia Kenyon
DOI: 10.1111/j.1474-9726.2006.00267.x
02/2007A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans
Genes & Development
S. Taubert
DOI: 10.1101/gad.1395406
05/2006E2F-Dependent Histone Acetylation and Recruitment of the Tip60 Acetyltransferase Complex to Chromatin in Late G1
Molecular and Cellular Biology
S. Taubert and C. Gorrini and S. R. Frank and T. Parisi and M. Fuchs and H.-M. Chan and D. M. Livingston and B. Amati
DOI: 10.1128/mcb.24.10.4546-4556.2004
04/2004E2F-dependent histone acetylation and recruitment of the Tip60 acetyltransferase complex to chromatin in late G
1
Molecular and Cellular Biology
Taubert, S. and Gorrini, C. and Frank, S.R. and Parisi, T. and Fuchs, M. and Chan, H.-M. and Livingston, D.M. and Amati, B.
DOI: 10.1128/MCB.24.10.4546-4556.2004
2004MYC recruits the TIP60 histone acetyltransferase complex to chromatin
EMBO reports
Scott R Frank and Tiziana Parisi and Stefan Taubert and Paula Fernandez and Miriam Fuchs and Ho-Man Chan and David M Livingston and Bruno Amati
DOI: 10.1038/sj.embor.embor861
06/2003Binding of c-Myc to chromatin mediates mitogen-induced acetylation of histone H4 and gene activation
Genes & Development
S. R. Frank
DOI: 10.1101/gad.906601
08/2001Function of the c-Myc oncoprotein in chromatin remodeling and transcription
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Bruno Amati and Scott R. Frank and Dubravka Donjerkovic and Stefan Taubert
DOI: 10.1016/s0304-419x(01)00020-8
03/2001Function of the c-Myc oncoprotein in chromatin remodeling and transcription
Biochimica et Biophysica Acta - Reviews on Cancer
Amati, B. and Frank, S.R. and Donjerkovic, D. and Taubert, S.
DOI: 10.1016/S0304-419X(01)00020-8
2001Pleiotropic effects of cAMP on germination, antibiotic biosynthesis and morphological development inStreptomyces coelicolor
Molecular Microbiology
Urs Süsstrunk and Josette Pidoux and Stefan Taubert and Agnes Ullmann and Charles J. Thompson
DOI: 10.1046/j.1365-2958.1998.01033.x
10/1998 - Research
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Current Projects
Conservation of MED15 function in mammals: Given the metabolic regulatory role of MDT-15 in C. elegans, we are testing whether MED15, its mammalian homologue, performs similar functions. Using candidate and unbiased genomic approaches we aim to identify MED15's transcriptional targets and biological functions in cultured cells. Additionally, we have generated tissue-specific MED15 loss-of-function and we are now investigating their metabolic and developmental phenotypes.Current Projects
MDT-15 interacting factors and molecular determinants: MDT-15 is the centre of a regulatory network that includes many Nuclear Hormone Receptors (NHRs). However, which, if any, part of MDT-15’s function these NHRs perform is unclear; moreover, we do not yet understand the molecular details of these interactions. Using advanced genetic, genomic, and biochemical methods, we are defining the individual roles of this network’s components.Current Projects
MDT-15 driven metabolic homeostasis: MDT-15 is required to maintain metabolic homeostasis in C. elegans, but how altered lipid balance affects organelle, cellular, and organismal function remains poorly understood. Our experiments aim to delineate the consequence of lipid imbalances in worms lacking mdt-15, and how lipid metabolism and oxidative stress responses impinge on organismal health and aging.Honours & AwardsCIHR Catalyst Grant (2010-2011)
NSERC Discovery Grant (2013-2018)
Canada Research Chair Tier 2 - renewal (2014-2019)
Research Group MembersSara Cristiano, Graduate Student
Meixia Dan, Research technician, Research technician
Gahan Diwan, Work Learn Student
Kelsie Doering, PhD Student
Glafira Ermakova, PhD Student
Dora Pak, Research Manager
Chiaki Shuzenji
Rachel Spencer, PhD Candidate
James Wu, Work Learn Student
Judith Yan, Doctoral Student
Congratulations CIHR Fall 2022 Project Grant recipients
Congratulations to the BC Children’s Hospital Research Institute (BCCHR) and Women’s Health Research Institute (WHRI) investigators and their teams who were awarded $8 million in funding through the Canadian Institutes of Health Research (CIHR) Fall 2022 Project Grant competition.
