TRPC and memory
TRPC channels are largely expressed in the brain, in particular in the hippocampus. We investigate the gating mechanisms of these channels and their role in neuronal excitability, synaptic plasticity, in memory formation and extinction. We also study how the amyloid-β precursor protein (APP) modulates synaptic activity by modifying the expression or the activity of neuronal ion transporters like the K+-Cl- cotransporter 2 (KCC2), and how this might interfere with memory processes.
Mechanosensitivity of TRP channels
Systemic osmoregulation is a vital process in which brain and kidney act in concert to regulate the water concentration in the organism. We study the signaling pathways involved in the process as well as the TRP channels sensing osmotic/ mechanical stimuli. The attached figure shows the activation of TRPV4 by a hypotonic solution (HTS) and its inhibition by HC067047.
Store-operated Ca2+ entry (SOCE) and cancer
SOCE, the main pathway allowing Ca2+ influx into non-excitable cells, is involved in tumorogenesis, cancer progression and chemoresistance. We showed that depletion of stromal interaction molecule 1 (STIM1), an ER Ca2+ sensor, and TRPC1 channel, reduced the SOCE and consequently the cisplatin-induced cytotoxicity in cancer cells. We now study the role of SOCE-induced entry of Ca2+ into the mitochondria, which is a major source of reactive oxygen species (ROS) within the cell that would be responsible for DNA damage response (DDR) and in turn, to apoptosis triggered by cisplatin.