mTORC1 signalling in disease
GTPase, Metabolism, MTOR
Research aim
Research aim
Disturbed cellular signaling lies at the heart of numerous hereditary and acquired diseases. Our research aims to resolve basic principles of signal transduction processes with as ultimate goal to contribute to therapeutic intervention.
About us
About us
Our research focus is the mTORC1 signaling pathway. mTORC1 is well known for its role in coordinating metabolism and its dysregulation is seen for example in cancer and metabolic syndrome. Mutations in mTOR or its regulators lead to disorders (mTORopathies) like Tuberous Sclerosis (TSC) and Birt-Hogg-Dubé (BHD) disease. TSC and BDH patients present with partially overlapping clinical manifestations that include skin fibromas, kidney tumors and epilepsy. In our studies we apply various model systems, mostly by generated via genome editing but also patient-derived cell cultures to address the following topics.
Regulation of mTORC1 signaling by growth factors and nutrients. Althouh the Rheb and Rag GTPases have been identified as intermediates in the sensing of growth factors and nutrients, our understanding of their regulation remains incomplete. We aim to further delineate the molecular mechanisms that control these GTPases to achieve proper mTORC1 activity.
Amino acid homeostasis under the control of mTORC1. mTORC1 activity is an important determinant of intra-cellular amino acid concentrations. This also holds true for neurons, where several amino acids function as neurotransmitter. We are studying how altered mTORC1 activity affects amino acid consumption and transport.
We collaborate with various research groups in the Netherlands that are also interested in mTORopathies and have complementary expertises.