Research topics

Our team is interested in the comprehension of intracellular and extracellular stress pathways following an “inside-outside” communication that must be deciphered in its molecular details. Organellar stress pathways (that operate inside cells) give rise to cellular manifestations (apoptosis, autophagy, senescence, necroptosis etc.) that in fine cause alterations in the extracellular milieu (outside cells) via the active or passive release of metabolites and macromolecules that act on receptors on neighboring cells and cause homeostatic or pathogenic reactions via inflammatory/immune or neuroendocrine pathways. By deciphering the rules that determine the “inside-outside” communication of stress, we attempt to understand the pathophysiology of aging and aging-related morbidities, placing special emphasis on cancer and its treatment with chemotherapy or immunotherapy. We attempt to achieve these goals by using metabolomics and cell biological high-throughput technology within a continuum between fundamental, pharmacological translational and clinical research.

The major aims of our team are:

• To decipher the major disease-relevant pathways of intracellular stress management (apoptosis, autophagy, senescence, necroptosis etc.) in the context of cell death or its avoidance.
• To understand the relationship between intracellular stress pathways and extracellular signaling with regard to metabolism, inflammatory/immune regulation and organismal homeostasis.
• To apply our knowledge on the fundamental cell biology/pathophysiology of cellular stress management to major age-related diseases, as well as the most frequent monogenetic human diseases, namely, cystic fibrosis and Wilson disease.
• To develop evidence-based strategies how changes in nutrition (reduction in caloric uptake, caloric restriction mimetics, interventions on the microbiome) can reduce obesity with its co-morbidities, as well as age-associated pathologies including cancer.
• To apply our fundamental research discoveries to the comprehension, prevention or treatment of oncogenesis and cancer progression following a continuum to translational and clinical research.
• To explore the mode of action of effective anticancer drugs with the scope to improve and broaden their utilization, laying emphasis on the idea that successful antineoplastics induce antitumor immune responses that are modulated by host genetic factors as well as by life style factors.

Technologies: The lab has built an internal cell biology platform. The team has generated numerous lentiviral constructs that express fluorescent biosensors for the detection of known immunogenic signals (e.g. CRT exposure, ATP secretion, HMGB1 release) or processes (e.g. autophagy, ER stress) and that can be combined with other sensors (that emit fluorescence at another wave length) to detect different parameters of apoptosis (mitochondrial outer membrane permeabilization, caspase activation, chromatin condensation), and necrosis (plasma membrane permeabilization). These biosensors have been used to generate stable cell lines in which different signals linked to cell death and/or immunogenicity are monitored at a per-cell level, thus facilitating the experimental design. In addition, the laboratory is fully equipped with four cytofluorometers, three conventional fluorescence microscopes, several automated fluorescence and luminometric plate readers, as well as all standard equipment for cell biology, molecular biology, and biochemical analyses. A metabolomics platform comprises liquid and gas chromatography coupled to GCQQQ 7000C and LCQQQ 6410 mass spectroscopy detectors (for targeted metabolomic analyses) or LCQTOF 6520 and Orbitrap Q Exactive detectors (for metabolomic profiling). This platform has been designed in a way that the large majority of metabolites (with a M.W. <1000 Da) can be simultaneously detected in clinical or experimental samples. The group has permanent access to a specific pathogen-free animal house with a small-animal imaging facility (which minimizes invasive diagnostics and reduces the number of animals required for experimentation), an immunohistochemical and histopathology service, an electron microscopy facility, an image analyzing platform, as well as permanent access to "omics" systems biology platforms that performs analyses of the transcriptome, micro-RNAome, CGH array, lipidome and proteome that is established at the Gustave Roussy Cancer Center. There is sufficient space (700 m2) to allow some 55 collaborators (9 staff scientists, 5 technicians, 12 post-docs, 15 graduate students, 3 master students etc.) to work comfortably and to accommodate additional personsonal to be recruited on several projects.

Institutions and research networks to which our laboratory is affiliated: Ligue contre le Cancer: The French Ligue against Cancer, the largest private organization for cancer research of the country, provides a special long-term grant (“équipe labellisée”) to Guido Kroemer’s laboratory. INSERM: The French Medical Research Council (INSERM) is a nationwide organization that covers all aspects of biomedical sciences. INSERM provides basic support to the Research Team « Apoptosis, Cancer & Immunity » (UMR1138) directed by Guido Kroemer and covers the salaries of staff scientists. INSERM also manages the salaries of several graduate students and post-docs who receive fellowships from the Ministry of Science or different charities. Gustave Roussy: Gustave Roussy Cancer Center (GR) takes care of the basic technical infrastructure of the research campus, including a specific pathogen-free animal facility, a small animal imaging platform and microarray as well as proteomics facilities. GR has collected more than 50 000 human cancer samples and is one of the world’s leading hospitals in clinical and translational cancer research, while conducting simultaneously several dozens of clinical assays. University Paris Descartes: Guido Kroemer has been nominated as a Full Professor at this prestigious university in 2010 and also has a position as a hospital practitioner at the Hôpital Européen George Pompidou (Hôpitaux de Paris, Assistance Publique). Worldwide innovative network (WIN): The laboratory is affiliated to this network, and Guido Kroemer is member of the scientific advisory board of WIN, an initiative that includes the world’s largest cancer-specific hospitals and that facilitates the exchange of patient data and samples and grants large cohort analyses. Institut National du Cancer (INCa) and Cancéropôle Ile-de-France. Several collaborative research project deals with the clinical exploration of anti-cancer immune responses. Agence Nationale pour la Recherche (ANR): Several projects are dealing with aspect of cell biology and one is organized under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases. LabEx “Immuno-Oncology”. Our laboratory coordinates the “Excellence laboratory” (LabEx) “Immuno-Oncology”, an initiative of the “Investissements d’avenir”. Paris Alliance of Cancer Research Institutes. Our laboratory participates to the “Paris Alliance of Cancer Research Institutes” (PACRI), a consortium of the major cancer research hospitals of the Paris region. LeDucq Foundation: We participate in a project dealing with the role of autophagy in cardiovascular diseases. RHU Torino Lumière: This network explores the possibility to stimulate anticancer immunosurveillance by manipulating the microbiome.