Mounia Chami

Institut de Pharmacologie Moléculaire et Cellulaire France

My research project is concentrated on the study of the role of calcium signaling at the subcellular level in physiological and pathological conditions. I am specialized in: 1) the measurements of calcium signalling dynamics in different intracellular compartments and microdomains (Endoplasmic Reticulum “ER”, mitochondria, cytoplasm) using recombinant targeted aequorin probes, fluorescent probes, and ratiometric/FRET calcium-based probes (Pericam and cameleon) ; and 2) in 3D morphological high resolution imaging of ER and mitochondrial structure using targeted recombinant fluorescent proteins (GFP-based). Using these tools and molecular biology approaches, I studied the molecular mechanisms associated to human liver carcinogenesis and the impact of calcium signaling in the control of cell proliferation and apoptosis. I demonstrated in different models the role of subcellular calcium signalling and ER-mitochondria structural communication in the accomplishment of apoptotic cell death. I cloned and characterized, a new spliced isoform of SERCA1 (Sarco-endoplsmic reticulum Calcium ATPase) encoding a C- terminal truncated SERCA1 protein (S1T) and demonstrated that S1T is an ER stress protein linking ER stress to mitochondrial apoptosis through selective calcium transfer from the ER to the mitochondria. My studies demonstrated also a primordial role for calcium in mitochondrial bioenergetics control in OXPHOS disease related to respiratory chain complex II defect. Taking advantage from this knowledge in calcium signaling field and experience in mitochondrial and ER organelle function, I oriented my studies on the molecular mechanisms underlying neurodegeneration in Alzheimer’s disease (AD). Indeed, AD is a multi-factorial pathology where calcium deregulation, mitochondrial dysfunction and ER stress may play a crucial role.

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