Overview

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

Activity of translation regulator eukaryotic elongation factor-2 kinase is increased in Parkinson disease brain and its inhibition reduces alpha synuclein toxicity
Acta Neuropathologica Communications
PubMed: 29961428
07/2018

NHR-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
06/2018

The 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
06/2017

Genomic 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
2017

eEF2K inhibition blocks Aß42 neurotoxicity by promoting an NRF2 antioxidant response
Acta Neuropathologica
Asad Jan and Brandon Jansonius and Alberto Delaidelli and Syam Prakash Somasekharan and Forum Bhanshali and Milène Vandal and Gian Luca Negri and Don Moerman and Ian MacKenzie and Frédéric Calon and Michael R. Hayden and Stefan Taubert and Poul H. Sorensen
DOI: 10.1007/s00401-016-1634-1
10/2016

Gain-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
09/2016

Caenorhabditis elegans Gets Metabolic Network Models
Cell Systems
Stefan Taubert
DOI: 10.1016/j.cels.2016.05.003
05/2016

Bacterial diet affects vulval organogenesis in Caenorhabditis elegans Mediator kinase module mutants
Matters
Jennifer Grants and Stefan Taubert
DOI: 10.19185/matters.201605000012
05/2016

s-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
10/2015

The 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
02/2015

The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans
Genetics
J. M. Grants and L. T. L. Ying and A. Yoda and C. C. You and H. Okano and H. Sawa and S. Taubert
DOI: 10.1534/genetics.115.180265
2015

Membrane lipids and the endoplasmic reticulum unfolded protein response: An interesting relationship
Worm
Nicole S Hou and Stefan Taubert
DOI: 10.4161/21624046.2014.962405
09/2014

Activation 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
05/2014

The conserved Mediator subunit MDT-15 is required for oxidative stress responses inCaenorhabditis elegans
Aging Cell
Grace Y. S. Goh and Katherine L. Martelli and Kulveer S. Parhar and Ada W. L. Kwong and Marcus A. Wong and Allan Mah and Nicole S. Hou and Stefan Taubert
DOI: 10.1111/acel.12154
09/2013

The 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
05/2013

Coordinate 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
04/2012

Repression 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
02/2012

Function and Regulation of Lipid Biology in Caenorhabditis elegans Aging
Frontiers in Physiology
Nicole Shangming Hou and Stefan Taubert
DOI: 10.3389/fphys.2012.00143
2012

Somatic 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
2012

Nuclear 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
03/2011

SET(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
09/2010

Functional 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
05/2010

The 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
02/2008

Lifespan 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
02/2007

A 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
05/2006

E2F-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
04/2004

MYC 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
06/2003

Binding 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
08/2001

Function 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
03/2001

Pleiotropic 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

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 & Awards

CIHR Catalyst Grant (2010-2011)

NSERC Discovery Grant (2013-2018)

Canada Research Chair Tier 2 - renewal (2014-2019)

Research Group Members

Zeena Aburegeba, Research Assistant
Deema Alhusari, Graduate student
Xuanjin Cheng, Postdoctoral Fellow
Kelsie Doering, Graduate student
Alice Huang, Research Assistant
Alexandre Kadhim, Graduate student
Luxcia Kugathasan, Undergraduate Student
Caitlyn Xu