Research

1) Translational and clinical studies.

Translational projects will rely on pre-existing and prospective collections of both solid tumors and leukemias, declared to the French Ministry of Research and included in the labeled biobank of Tours CHU.
Collections will be used for proteomic, transcriptomic and metabolic characterization, as well as to determine their lipid composition (lipidomics), in relation to tumor aggressiveness.
Data obtained from the collections of human samples will lead to hypotheses to be mechanistically tested. Conversely, bioresources from human tumors will allow to validate mechanistic findings and genomic signatures.

2) Calcium signaling.

WP1. Identification of the lipidome from paired adipose tissues and tumors associated with onco-complexes expression (calciome) and link to tumor aggressiveness.
WP2. Characterization of calcium controlling lipid-sensitive ion channel complexes.
WP3. Biological effects of lipid candidates and functional characterization of their mechanism of action.

3) Energy metabolism.

WP1. Mechanisms of action of lipids on metabolism as modulators of cancer complications.
WP2 Original strategies for optimizing metabolic analyses and identification of metabolic reprogramming parameters as potential clinical biomarkers of cancer progression.
WP3. Nutritional and pharmacological approaches for the modulation of metabolic changes.

Amélie Bura : "Mitochondrial calcium signaling in cancer cells as a modulator of anti-tumor immune response". Thesis under the supervision of Maxime Guéguinou.

Camille Caussette : "Targeting of mitochondrial calcium signaling in colorectal cancer". Thesis under the joint supervision of William Raoul (50%) et Maxime Guéguinou (50%)

Petra Cutuk : "Regulation of SKCa channels by the cAMP/PKA pathway in cancer cells: development of novel near-infrared optical imaging tools". Thesis under the joint supervision of Christophe Vandier (50%) et Stéphane Petoud (50%, CBM CNRS, University of Orléans)

Aude Lemettre : " Development of antibodies inhibiting SKCa channel activity as a new therapeutic strategy in cancer". Thesis under the supervision of Marie Potier-Cartereau

Anaïs Pascal : "Mechanisms involved in chemotherapy-induced myosteatosis: What roles for mitochondrial metabolism?". Thesis under the supervision of Stéphane Servais (75%). Co-supervision of Vera Mazurak (25%, University of Alberta, Canada)

Lipid chemistry - analysis and synthesis: extraction of lipids from biological tissues (cell lines, adipose tissue, liver, muscle, tumors…), purification of lipids (phospholipids, triglycerides, ether-lipids, sterols…), qualitative and quantitative analyses of lipids

Mitochondrial bioenergetics: studies on isolated mitochondria, permeabilized and whole cells, permeabilized skeletal muscle fibers, mitochondrial bioenergetics analyses (oxygen consumption, ATP synthesis, efficiency of ATP synthesis, membrane potential, ROS, Permeability Transition Pore…).
 
Single-cell electrophysiology: patch-clamp studies (« current-clamp » and « voltage-clamp » modes, « whole-cell» and « inside out » configurations), studies of ion channels (NaV, BKCa, IKCa, SK3, SK2 and SK1, P2X, Orai, TRPC, TRAAK…)

Cell biology: tests for 2D and 3D cancer cell invasiveness, single-cell or collective migration, proliferation and cell viability, fractionation and functional analyses of invadopodia, proteases activity in cell extracts, supernatants, in living and fixed cells, cell line and primary cultures…
 
Fluorescence imaging and spectrofluorimetry: calcium, sodium, protons, membrane potential, ROS.
 
Molecular biology: nucleic acids (RT-qPCR, plasmid amplification, site-directed mutagenesis, gene reporter assays) and proteins (western blotting, immunoprecipitation, membrane fractionation on sucrose gradients).
 
Animal models: xenogenic and syngenic orthotopic or ectopic graft models of breast cancer cells in immunodepressed or immunocompetent mice, NMU model of mammary carcinogenesis in rats, rat models of cancer cachexia, spontaneous models of mammary tumors (PyMT) in mice, transgenic, knock-out and tissue-specific knock-out animal models (PyMTTg, TRAMP, Caveolin-1, Caveolin-2, Caveolin-3).
 
Anatomopathology and Immunohistochemistry: anatomopathology and immunohistochemical analyses on different cancers (breast, prostate, colon…) of murine models or clinical samples from patients.