Nicolas Demaurex's lab focuses on the mechanisms controlling the ionic homeostasis of innate immune cells, in particular the mechanisms regulating calcium channels activated by a decrease in calcium concentration in the endoplasmic reticulum. These so-called store-operated channels generate signals controlling gene expression, cell proliferation and the secretion of inflammatory mediators by immune cells.
His laboratory has helped establish the molecular basis of membrane contact sites in the activation of store-operated calcium channels and the physiological significance of these channels in the regulation of neutrophil and dendritic cell functions. Work in progress in the laboratory is focused on understanding the role of the proteins STIM, ORAI, and Hv1 in leukocyte trafficking and in regulating the bactericidal activity of neutrophils.
His core expertise is in the cell physiology of ion transport, with the use ion imaging and electrophysiological approaches to record the activity of ion channels and transporters in cellular membranes, and 3D electron tomography to study the architecture of membrane contact sites.
He has a deep expertise in quantitative measurements of ionic activities inside intracellular compartments, using dyes or genetic probes to record calcium and pH changes within organelles such as the endoplasmic reticulum, mitochondria, and endo-lysosomes.
Nunes-Hasler P, Maschalidi S, Lippens C, Castelbou C, Bouvet S, Guido D, Bermont F, Bassoy EY, Page N, Merkler D, Hugues S, Martinvalet D, Manoury B, & Demaurex N. STIM1 promotes migration, phagosomal maturation and antigen cross-presentation in dendritic cells. Nat Commun 8:1852 (2017)
Sauc S, Bulla M, Nunes P, Orci L, Marchetti A, Antigny F, Bernheim L, Cosson P, Frieden, & Demaurex N. STIM1L traps and gates Orai1 channels without remodeling the cortical ER. J. Cell Sci 128:1568-79 (2015)
Nunes P, Cornut D, Bochet V, Hasler U, Oh-Hora M, Waldburger J-M, & Demaurex N. STIM1 Juxtaposes ER to Phagosomes, Generating Ca2+ Hotspots that Boost Phagocytosis. Current Biology 22:1990-7 (2012)
El Chemaly A, Okochi Y, Sasaki M, Arnaudeau S, Okamura Y & Demaurex N. VSOP/Hv1 proton channels sustain calcium entry, neutrophil migration, and superoxide production by limiting cell depolarization and acidification, J. Exp. Med 207:129-39 (2010)
Bánfi B, Maturana A, Jaconi S, Arnaudeau S, Laforge T, Sinha B, Ligeti E, Demaurex N & Krause KH. A mammalian H+ channel, generated through alternative splicing of the NADPH oxidase homologue NOH-1. Science 287: 138-42 (2000)March 24, 2022
Immune cell trafficking and maturation