- 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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Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans
bioRxiv
DOI: 10.1101/2024.03.20.585993
2024The unfolded protein response of the endoplasmic reticulum protects Caenorhabditis elegans against DNA damage caused by stalled replication forks
G3: Genes, Genomes, Genetics
DOI: 10.1093/G3JOURNAL/JKAE017
2024Methods to extract and study the biological effects of murine gut microbiota using Caenorhabditis elegans as a screening host
PLoS ONE
DOI: 10.1371/journal.pone.0281887
2023Mediator subunit MDT-15 promotes expression of propionic acid breakdown genes to prevent embryonic lethality in Caenorhabditis elegans
G3: Genes, Genomes, Genetics
DOI: 10.1093/g3journal/jkad087
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
Cheng, X. and Liu, Y. and Wang, J. and Chen, Y. and Robertson, A.G. and Zhang, X. and Jones, S.J.M. and Taubert, S.
DOI: 10.1093/bib/bbac090
2022Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans
eLife
Doering, K.R.S. and Cheng, X. and Milburn, L. and Ratnappan, R. and Ghazi, A. and Miller, D.L. and Taubert, S.
DOI: 10.7554/eLife.67911
2022eVITTA: 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 inCaenorhabditis 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
2021cSurvival: A web resource for biomarker interactions in cancer outcomes
bioRxiv
Cheng, X. and Liu, Y. and Wang, J. and Chen, Y. and Robertson, A.G. and Zhang, X. and Jones, S.J.M. and Taubert, S.
DOI: 10.1101/2021.11.15.468756
2021NHR-49/PPAR-a and HLH-30/TFEB promoteC. eleganshost 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
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
Doering, K.R.S. and Taubert, S.
DOI: 10.1371/journal.pbio.3000236
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
2019C. 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
07/2018Activity of translation regulator eukaryotic elongation factor-2 kinase is increased in Parkinson disease brain and its inhibition reduces alpha synuclein toxicity
Acta neuropathologica communications
Jan, A. and Jansonius, B. and Delaidelli, A. and Bhanshali, F. and An, Y.A. and Ferreira, N. and Smits, L.M. and Negri, G.L. and Schwamborn, J.C. and Jensen, P.H. and Mackenzie, I.R. and Taubert, S. and Sorensen, P.H.
DOI: 10.1186/s40478-018-0554-9
2018NHR-49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting
Aging Cell
Goh, G.Y.S. and Winter, J.J. and Bhanshali, F. and Doering, K.R.S. and Lai, R. and Lee, K. and Veal, E.A. and Taubert, S.
DOI: 10.1111/acel.12743
2018eEF2K 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
2017The R148.3 gene modulates Caenorhabditis elegans lifespan and fat metabolism
G3: Genes, Genomes, Genetics
Roy-Bellavance, C. and Grants, J.M. and Miard, S. and Lee, K. and Rondeau, ?. and Guillemette, C. and Simard, M.J. and Taubert, S. and Picard, F.
DOI: 10.1534/g3.117.041681
2017Genomic and cytogenetic characterization of a balanced translocation disrupting NUP98
Cytogenetic and Genome Research
Thibodeau, M.L. and Steinraths, M. and Brown, L. and Zong, Z. and Shomer, N. and Taubert, S. and Mungall, K.L. and Ma, Y.P. and Mueller, R. and Birol, I. and Lehman, A.
DOI: 10.1159/000479463
2017Bacterial diet affects vulval organogenesis in Caenorhabditis elegans Mediator kinase module mutants
Matters
DOI: 10.19185/matters.201605000012
05/2016Caenorhabditis elegans Gets Metabolic Network Models
Cell Systems
Taubert, S.
DOI: 10.1016/j.cels.2016.05.003
2016The mediator kinase module restrains epidermal growth factor receptor signaling and represses vulval cell fate specification in Caenorhabditis elegans
Genetics
Grants, J.M. and Ying, L.T.L. and Yoda, A. and You, C.C. and Okano, H. and Sawa, H. and Taubert, S.
DOI: 10.1534/genetics.115.180265
2016Gain-of-function alleles in caenorhabditis elegans nuclear hormone receptor nhr-49 are functionally distinct
PLoS ONE
Lee, K. and Goh, G.Y.S. and Wong, M.A. and Klassen, T.L. and Taubert, S.
DOI: 10.1371/journal.pone.0162708
2016The Mediator complex of Caenorhabditis elegans: Insights into the developmental and physiological roles of a conserved transcriptional coregulator
Nucleic Acids Research
Grants, J.M. and Goh, G.Y.S. and Taubert, S.
DOI: 10.1093/nar/gkv037
2015S-adenosylmethionine levels govern innate immunity through distinct methylation-dependent pathways
Cell Metabolism
Ding, W. and Smulan, L.J. and Hou, N.S. and Taubert, S. and Watts, J.L. and Walker, A.K.
DOI: 10.1016/j.cmet.2015.07.013
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
09/2014The 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
2014Activation of the endoplasmic reticulum unfolded protein response by lipid disequilibrium without disturbed proteostasis in vivo
Proceedings of the National Academy of Sciences of the United States of America
Hou, N.S. and Gutschmidt, A. and Choi, D.Y. and Pather, K. and Shi, X. and Watts, J.L. and Hoppe, T. and Taubert, S.
DOI: 10.1073/pnas.1318262111
2014The C. elegans CDK8 Mediator module regulates axon guidance decisions in the ventral nerve cord and during dorsal axon navigation
Developmental Biology
Steimel, A. and Suh, J. and Hussainkhel, A. and Deheshi, S. and Grants, J.M. and Zapf, R. and Moerman, D.G. and Taubert, S. and Hutter, H.
DOI: 10.1016/j.ydbio.2013.02.009
2013Function and regulation of lipid biology in Caenorhabditis elegans aging
Frontiers in Physiology
Hou, N.S. and Taubert, S.
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
2012Repression of a potassium channel by nuclear hormone receptor and TGF-ß signaling modulates insulin signaling in Caenorhabditis elegans
PLoS Genetics
Park, D. and Jones, K.L. and Lee, H. and Snutch, T.P. and Taubert, S. and Riddle, D.L.
DOI: 10.1371/journal.pgen.1002519
2012Coordinate regulation of lipid metabolism by novel nuclear receptor partnerships
PLoS Genetics
Pathare, P.P. and Lin, A. and Bornfeldt, K.E. and Taubert, S. and van Gilst, M.R.
DOI: 10.1371/journal.pgen.1002645
2012Nuclear hormone receptors in nematodes: Evolution and function
Molecular and Cellular Endocrinology
Taubert, S. and Ward, J.D. and Yamamoto, K.R.
DOI: 10.1016/j.mce.2010.04.021
2011Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network
Molecular Systems Biology
Arda, H.E. and Taubert, S. and MacNeil, L.T. and Conine, C.C. and Tsuda, B. and Van Gilst, M. and Sequerra, R. and Doucette-Stamm, L. and Yamamoto, K.R. and Walhout, A.J.M.
DOI: 10.1038/msb.2010.23
2010SET(BP1)-ing the stage for a better understanding of Schinzel - Giedion syndrome
Clinical Genetics
Taubert, S.
DOI: 10.1111/j.1399-0004.2010.01505.x
2010The mediator subunit MDT-15 confers metabolic adaptation to ingested material
PLoS Genetics
Taubert, S. and Hansen, M. and Van Gilst, M.R. and Cooper, S.B. and Yamamoto, K.R.
DOI: 10.1371/journal.pgen.1000021
2008Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans
Aging Cell
Hansen, M. and Taubert, S. and Crawford, D. and Libina, N. and Lee, S.-J. and Kenyon, C.
DOI: 10.1111/j.1474-9726.2006.00267.x
2007A mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans
Genes and Development
Taubert, S. and Van Gilst, M.R. and Hansen, M. and Yamamoto, K.R.
DOI: 10.1101/gad.1395406
2006E2F-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
Frank, S.R. and Parisi, T. and Taubert, S. and Fernandez, P. and Fuchs, M. and Chan, H.-M. and Livingston, D.M. and Amati, B.
DOI: 10.1038/sj.embor.embor861
2003Binding of c-Myc to chromatin mediates mitogen-induced acetylation of histone H4 and gene activation
Genes and Development
Frank, S.R. and Schroeder, M. and Fernandez, P. and Taubert, S. and Amati, B.
DOI: 10.1101/gad.906601
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 in Streptomyces coelicolor
Molecular Microbiology
Süsstrunk, U. and Pidoux, J. and Taubert, S. and Ullmann, A. and Thompson, C.J.
DOI: 10.1046/j.1365-2958.1998.01033.x
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
Kelsie Doering, Visiting Faculty
Glafira Ermakova, PhD Student
Judy Kim, Undergraduate Volunteer
Dora Pak, Research Manager
Chiaki Shuzenji
Rachel Spencer, PhD Candidate
Shane Taylor, Postdoctoral Fellow
James Wu, Work Learn Student
Judith Yan, Doctoral Student
Janice Zhan, NSERC USRA Summer Student
Estelle Zhang, Graduate Research Assistant
New study makes key findings in potential advancement of diabetes cure
New research published in Nature Communications, identifies a key molecule that might be critical for the development of stem cell-based therapies for treating type 1 diabetes.
