Publications de Evan Graehl Williams

The mouse metallomic landscape of aging and metabolism

Johan Auwerx, Richardus Houtkooper, Evan Graehl Williams, Pooja Jha, Jean-David Horacio Morel, Ludger Jan Elzuë Goeminne

The metallome is crucial for normal cell functioning but remains largely overlooked in mammals. Here the authors analyze the metallome and copper and zinc isotope compositions in aging mice and show networks of interactions that are organ-specific, age-dep ...

Nature Research2022

A platform for experimental precision medicine: The extended BXD mouse family

Johan Auwerx, Evan Graehl Williams

The challenge of precision medicine is to model complex interactions among DNA variants, phenotypes, development, environments, and treatments. We address this challenge by expanding the BXD family of mice to 140 fully isogenic strains, creating a uniquely ...

CELL PRESS2021

Gene-by-environment modulation of lifespan and weight gain in the murine BXD family

Johan Auwerx, Evan Graehl Williams, Maroun Bou Sleiman, Pooja Jha

How lifespan and body weight vary as a function of diet and genetic differences is not well understood. Here we quantify the impact of differences in diet on lifespan in a genetically diverse family of female mice, split into matched isogenic cohorts fed a ...

NATURE PORTFOLIO2021

Mild inborn errors of metabolism in commonly used inbred mouse strains

Johan Auwerx, Evan Graehl Williams, Wei Zhang

Inbred mouse strains are a cornerstone of translational research but paradoxically many strains carry mild inborn errors of metabolism. For example, alpha-aminoadipic acidemia and branched-chain ketoacid dehydrogenase deficiency are known in C57BL/6J mice. ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2019

Diet modulates cecum bacterial diversity and physiological phenotypes across the BXD mouse genetic reference population

Johan Auwerx, Evan Graehl Williams

The BXD family has become one of the preeminent genetic reference populations to understand the genetic and environmental control of phenotypic variation. Here we evaluate the responses to different levels of fat in the diet using both chow diet (CD, 13-18 ...

2019

A new class of protein biomarkers based on subcellular distribution: application to a mouse liver cancer model

Ruedi Aebersold, Kristina Schoonjans, Evan Graehl Williams, Pan Xu, Amir Banaei Esfahani, Vera Monica Lemos Da Silva, Chen Li

To-date, most proteomic studies aimed at discovering tissue-based cancer biomarkers have compared the quantity of selected proteins between case and control groups. However, proteins generally function in association with other proteins to form modules loc ...

Nature Research2019

Genetic cartography of longevity in humans and mice: Current landscape and horizons

Sylvain Roy, Johan Auwerx, Evan Graehl Williams, Maroun Bou Sleiman

2018

Genetic Regulation of Plasma Lipid Species and Their Association with Metabolic Phenotypes

Johan Auwerx, Evan Graehl Williams, Maroun Bou Sleiman, Karim Laurent Gariani, Pooja Jha, Pedro Moral Quiros

2018

Systems Analyses Reveal Physiological Roles and Genetic Regulators of Liver Lipid Species

Johan Auwerx, Evan Graehl Williams, Léo Aurélio Diserens, Maroun Bou Sleiman, Karim Laurent Gariani, Pooja Jha, Pedro Moral Quiros

2018

Quantifying and Localizing the Mitochondrial Proteome Across Five Tissues in A Mouse Population

Ruedi Aebersold, Johan Auwerx, Evan Graehl Williams, Dongryeol Ryu, Pooja Jha, Jiayi Lan, Jun Yong Kim, Moaraj Hasan

We have used SWATH mass spectrometry to quantify 3648 proteins across 76 proteomes collected from genetically diverse BXD mouse strains in two fractions (mitochondria and total cell) from five tissues: liver, quadriceps, heart, brain, and brown adipose (BA ...

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC2018

Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents

Patrick Aebischer, Maria del Carmen Sandi Perez, Elena Katsyuba, Johan Auwerx, Damien Sébastien Huzard, Norman Lionel Moullan, Pénélope Andreux, Evan Graehl Williams, Dongryeol Ryu, Laurent Mouchiroud, Giuseppe Lo Sasso, Pooja Jha

The biological effects of urolithins remain poorly characterized, despite wide-spread human exposure via the dietary consumption of their metabolic precursors, the ellagitannins, which are found in the pomegranate fruit, as well as in nuts and berries. We ...

2016

Two Conserved Histone Demethylases Regulate Mitochondrial Stress-Induced Longevity

Johan Auwerx, Evan Graehl Williams, Laurent Mouchiroud, Virginija Jovaisaite

Across eukaryotic species, mild mitochondrial stress can have beneficial effects on the lifespan of organisms. Mitochondrial dysfunction activates an unfolded protein response (UPR(mt)), a stress signaling mechanism designed to ensure mitochondrial homeost ...

Cell Press2016

Systems proteomics of liver mitochondria function

Sébastien Dubuis, Ruedi Aebersold, Johan Auwerx, Evan Graehl Williams, Tiffany Amariuta, Pooja Jha

Recent improvements in quantitative proteomics approaches, including Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS), permit reproducible large-scale protein measurements across diverse cohorts. Together with genomics, transcriptom ...

American Association for the Advancement of Science2016

Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research

Michael Vincent Frochaux, Bart Deplancke, Johan Auwerx, Richardus Houtkooper, Norman Lionel Moullan, Evan Graehl Williams, Dongryeol Ryu, Adrienne Joëlle Laurence Mottis, Laurent Mouchiroud, Virginija Jovaisaite, Xu Wang

In recent years, tetracyclines, such as doxycycline, have become broadly used to control gene expression by virtue of the Tet-on/Tet-off systems. However, the wide range of direct effects of tetracycline use has not been fully appreciated. We show here tha ...

Elsevier2015

The Convergence of Systems and Reductionist Approaches in Complex Trait Analysis

Johan Auwerx, Evan Graehl Williams

Research into the genetic and environmental factors behind complex trait variation has traditionally been segregated into distinct scientific camps. The reductionist approach aims to decrypt phenotypic variability bit by bit, founded on the underlying hypo ...

2015

An evolutionarily conserved role for the aryl hydrocarbon receptor in the regulation of movement

Michael Vincent Frochaux, Bart Deplancke, Johan Auwerx, Pénélope Andreux, Evan Graehl Williams, Laurent Mouchiroud

The BXD genetic reference population is a recombinant inbred panel descended from crosses between the C57BL/6 (B6) and DBA/2 (D2) strains of mice, which segregate for about 5 million sequence variants. Recently, some of these variants have been established ...

Public Library of Science2014

Pharmacological Inhibition of Poly(ADP-Ribose) Polymerases Improves Fitness and Mitochondrial Function in Skeletal Muscle

Kristina Schoonjans, Johan Auwerx, Carlos Canto Alvarez, Norman Lionel Moullan, Evan Graehl Williams, Eija Riitta Pirinen, Laurent Mouchiroud, Hongbo Zhang, Keir Joe Menzies, Laia Morato Fornaguera, Wei Li

We previously demonstrated that the deletion of the poly(ADP-ribose) polymerase (Parp)-1 gene in mice enhances oxidative metabolism, thereby protecting against diet-induced obesity. However, the therapeutic use of PARP inhibitors to enhance mitochondrial f ...

Cell Press2014

Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population

Sébastien Dubuis, Ruedi Aebersold, Johan Auwerx, Evan Graehl Williams, Adrienne Joëlle Laurence Mottis, Virginija Jovaisaite

The manner by which genotype and environment affect complex phenotypes is one of the fundamental questions in biology. In this study, we quantified the transcriptome--a subset of the metabolome--and, using targeted proteomics, quantified a subset of the li ...

Cell Press2014

A Systems Approach to Identify Genetic and Environmental Regulators of Metabolism

Evan Graehl Williams

For more than a century, it has been recognized that our genetic inheritance and our environment interact to shape who we are and how we act (nature vs. nurture ), and the study of genetics has allowed us to explain why traits can vary dramatically betwee ...

EPFL2014

NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function

Kristina Schoonjans, Johan Auwerx, Carlos Canto Alvarez, Hiroyasu Yamamoto, Evan Graehl Williams, Laurent Mouchiroud

Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enha ...

2011