Gene Regulatory Control in Disease (GeneControl)
The regulation of gene expression is key to understanding cell behavior. It is precisely controlled to ensure that specific genes are expressed at the appropriate times and levels in response to various genetic and environmental signals, which determines the biological processes at work in the cell. Its disruption therefore often leads to disease.
Using both experimental and computational approaches, our laboratory aims to deconstruct the mechanistic basis for control of gene expression in developmental and pathological contexts at the level of single genes to entire genomes. We are interested in multiple aspects of gene expression control, including transcriptional, translational and post-translational control mechanisms with a particular focus on nerve disorders, liver disease and cancer.
Research Lines
- Nerve Disorders: The work in the laboratory addresses a set of interlocking issues in Schwann cell biology, ranging from axonal myelination to the response of Schwann cells to pathological conditions, including nerve injury, genetic disorders, immune cell attack and microbial infections.
- Liver Disease: We are investigating the molecular mechanisms underlying the hepatic cellular responses to chronic liver diseases of various etiologies, including non-alcoholic fatty liver disease (NAFLD), drugs, and cholestatic disease, as well as the hepatic regenerative response after liver resection.
- Cancer: We are focused on the identification of therapeutical targets for neurofibromatosis type 1 and malignant peripheral nerve sheath tumours (MPNST) Our research employs a variety of model organisms (mice models and patient samples) and is built on a multidisciplinary approach involving an array of modern techniques in biochemistry and molecular, cellular, and structural biology, as well as bioinformatic analyses, high-throughput sequencing and -OMICS technologies.
Members
Selected publications
Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals
HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis.
Methionine and SAMe levels are critical regulators of PP2A activity modulating lipophagy during steatosis.
The RNA-binding protein human antigen R controls global changes in gene expression during Schwann cell development.
Human antigen R contributes to hepatic stellate cell activation and liver fibrosis.
Hepatology.
A central role for the ERK-signaling pathway in controlling Schwann cell plasticity and peripheral nerve regeneration in vivo.
c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration.
Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity.