MRC London Institute of Medical Sciences (LMS)
The MRC London Institute of Medical Sciences (LMS) is a vibrant research environment where scientists, clinicians and patients collaborate to advance the understanding of biology and its application to medicine. The LMS pursues world-leading discovery science with a particular emphasis on interdisciplinary approaches involving engineering and the physical sciences. Our research aims to address major health challenges (such as obesity, diabetes, heart disease and cancer), investigate the interplay between genes and environment, and understand the molecular basis of disease, development and ageing.
Aryl Hydrocarbon Receptor (AHR)
The main focus of our group is the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that belongs to the basic helix-loop-helix/PAS family of transcriptional regulators. AHR pathway activation by natural ligands is tightly controlled and ligand binding to AHR leads to induction of cytochrome P4501 (CYP1) enzymes, which rapidly metabolize AHR ligands leading to signal termination. This potent negative feedback system ensures transient activation of AHR-dependent gene programs and means the AHR pathway is uniquely sensitive to alterations in ligand exposure. As such, AHR acts as a molecular decoder of dynamic environmental cues ranging from dietary nutrient composition and metabolic state to microbial metabolites. However, much remains to be learned about the physiological role of AHR ligands, and the mechanisms by which AHR activation results in functional changes on the cellular and organismal level.
Our research group utilizes in vitro and in vivo models in order to unravel the complexities of AHR pathway regulation in health and disease. Our aim is to comprehensively answer the following questions:
What are the cellular targets of AHR in health and disease?
What are the molecular pathways downstream of AHR activation?
What is the role of natural AHR ligands in health and disease?
We believe that a better understanding of AHR biology may facilitate the discovery of novel therapeutics for the treatment of chronic inflammatory diseases and metabolic syndrome.
We are always interested in applications from enthusiastic students and postdocs, especially if you are keen to apply for independent funding!
Group Leader, Penny-Pincher
I completed my MSci in Immunology at the University of Glasgow in 2008. I then took up a PhD studentship in Fiona Powrie’s lab at the University of Oxford. During my time in Fiona’s lab, I investigated cytokine networks that contribute to chronic intestinal inflammation with a particular focus on Treg and Th17 cells.
I moved to London in 2013 to conduct my postdoctoral studies in the lab of Gitta Stockinger at the Francis Crick Institute. While in Gitta’s lab, I became fascinated by the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor capable of recognizing dietary components and microbiota metabolites.
We are now continuing to study this versatile receptor in the context of immunity and metabolic disease in my newly established research group at the London Institute of Medical Sciences (LMS).
PhD Student, Queen of Westerns
I completed my Master Degree in microbiology at the University of Leeds in 2017. My project mainly focused on isolating in vitro inhibitors for RhoA. Shortly after, I joined the Brodsky Lab at UCL as a research technician working on the role of different isoforms of the clathrin heavy chain in GLUT4 trafficking.
I started my PhD project in Chris’ lab in October 2018. My main project aim is to understand the role of AHR in metabolic disease. This includes understanding on a cellular and molecular level the activation and regulation of AHR in specific tissues and cell types and how this may contribute to metabolic disease.
Julia Vlachaki Walker
PhD Student, Supersonicator
Following a BSc in Neuroscience in the University of Dundee, I took up a 6-month voluntary position in Dr Will Fuller’s lab studying the human phospholemman protein. I then accepted a 5-year research technician position under the supervision of Dr Craig Beall starting in the University of Dundee, with a relocation to the University of Exeter. There I investigated the response of astrocytes to hypoglycaemia, and their potential role in the defective counter-regulatory response to hypoglycaemia in diabetes. I simultaneously completed a part-time MPhil on the same subject. For my work I utilised both in vivo and in vitro approaches, with a strong focus on AMPK, purinergic and inflammatory signaling and metabolism.
Post-Doc, FACS Professional
I completed my PhD at the University of Birmingham in 2018 under the tutelage of Dr Zania Stamataki where I worked on CD4+T cells in the human liver. Investigating the consequences of both migration of these cells into the liver, and of long-term interactions with the liver microenvironment gave me a broad range of experience in cellular immunology. I followed this up at the end of 2018 with a short project in Prof. Mala Maini’s lab working on T cell responses in hepatitis B viral infection of the liver.
Now a postdoc in Chris’ lab, I aim to combine my passion for immunology with the lab’s expertise on metabolism research. My projects focus on understanding the immune compartment in metabolic tissues, and determining how AHR regulates the biology of these populations.
Metidji A, Omenetti S, Crotta S, Li Y, Nye E, RossE, Li V, Maradana MR, Schiering C*, and Stockinger B*. 2018. The environmental sensor AHR protects from inflammatory damage by maintaining intestinal stem cell homeostasis and barrier integrity. Immunity 49: 353-362 *joint corresponding authors
Schiering C, Vonk A, Das S, Stockinger B, Wincent E. 2018. Cytochrome P4501-inhibiting chemicals amplify aryl hydrocarbon receptor activation and IL-22 production in T helper 17 cells. Biochem Pharmacol 151: 47-58
Schiering C, Wincent E, Metidji A, Iseppon A, Li Y, Potocnik AJ, Omenetti S, Henderson CJ, Wolf CR, Nebert DW, Stockinger B. 2017. Feedback control of AHR signalling regulates intestinal immunity. Nature 542: 242-5
Krausgruber T*, Schiering C*, Adelmann K, Harrison OJ, Chomka A, Pearson C, Ahern PP, Shale M, Oukka M, Powrie F. 2016. T-bet is a key modulator of IL-23-driven pathogenic CD4(+) T cell responses in the intestine. Nat Commun 7: 11627
*joint first author
Schiering C, Krausgruber T, Chomka A, Frohlich A, Adelmann K, Wohlfert EA, Pott J, Griseri T, Bollrath J, Hegazy AN, Harrison OJ, Owens BM, Lohning M, Belkaid Y, Fallon PG, Powrie F. 2014. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 513: 564-8