From investigations into the molecular and functional heterogeneity of brain macrophages to translation into novel therapeutic approaches for the treatment of cancer and neurodegenerative diseases.
The Brain and Systems Immunology team led by Kiavash Movahedi investigates neuro-immune crosstalk in the brain. We have a particular interest in brain macrophages and seek to understand their ontogeny, diversity and role in shaping brain homeostasis and disease. To study the brain immune landscape and neuroinflammation, we employ cutting-edge technologies. This includes single-cell multi-omic analysis (e.g CITE-seq via 10x genomics, high parametric spatial analysis using Akoya Phenocycler-Fusion), genome engineering and induced-pluripotent stem cell technology. Importantly, we aim for translational research that can provide new treatment options for brain disease, including for neurodegenerative disorders (Alzheimer's disease, frontotemporal dementia) and primary brain tumors (glioblastoma). Our lab also has a strong interest for pioneering innovative cell therapy approaches that are based on macrophage engineering and replacement
PUBLICATIONS
Today's challenge for precision medicine involves the integration of the impact of molecular clocks on drug pharmacokinetics, toxicity, and efficacy toward personalized chronotherapy. Meaningful improvements of tolerability and/or efficacy of medications through proper administration timing have been confirmed over the past decade for immunotherapy and chemotherapy against cancer, as well as for commonly used pharmacological agents in cardiovascular, metabolic, inflammatory, and neurological...
Agonistic αCD40 therapy has been shown to inhibit cancer progression in only a fraction of patients. Understanding the cancer cell-intrinsic and microenvironmental determinants of αCD40 therapy response is therefore crucial to identify responsive patient populations and to design efficient combinatorial treatments. Here, we show that the therapeutic efficacy of αCD40 in subcutaneous melanoma relies on preexisting, type 1 classical dendritic cell (cDC1)-primed CD8+ T cells. However, after...
Macrophages are diverse immune cells populating all tissues and adopting a unique tissue-specific identity. Breast macrophages play an essential role in the development and function of the mammary gland over one's lifetime. In the recent years, with the development of fate-mapping, imaging and scRNA-seq technologies we grew a better understanding of the origin, heterogeneity and function of mammary macrophages in homeostasis but also during breast cancer development. Here, we aim to provide a...
The circadian clock coordinates biological and physiological functions to day/night cycles. The perturbation of the circadian clock increases cancer risk and affects cancer progression. Here, we studied how BMAL1 knockdown (BMAL1-KD) by shRNA affects the epithelial-mesenchymal transition (EMT), a critical early event in the invasion and metastasis of colorectal carcinoma (CRC). In corresponding to a gene set enrichment analysis, which showed a significant enrichment of EMT and invasive...
The circadian rhythm is a major environmental regulator of plants and animal physiology. The alternation of days and nights is translated at the cell and tissue level thanks to a molecular machinery, called the circadian clock. This clock controls in particular numerous endocrine functions, and its imbalances can have serious consequences on homeostasis. This is particularly true for the development of endocrine-related cancers, like breast, ovarian and prostate cancer. Circadian rhythm disorder...
Epithelial-Mesenchymal Transition (EMT) and its reciprocal Mesenchymal-Epithelial Transition (MET) occur naturally as a cycling process during embryonic and foetal development. The capacity of such iterative cycles to drive cell fate and cellular and molecular behaviour in physiology or pathology remains unclear. We describe here a protocol to induce successive cycles of EMT/MET in an untransformed human mammary epithelial cell line (MCF10A) as well as the necessary controls for cycle...
CONCLUSIONS: Atherosclerosis-associated macrophage polarisation dramatically affects lipid handling capacity underpinned by major transcriptomic changes and altered protein levels in lipid-handling gene expression. This leads to phenotype-specific differences in LDL uptake, cellular cholesterol levels and cholesterol efflux, informing how the plaque environment influences atherosclerosis progression by influencing macrophage phenotypes.
Breast cancer is the most common type of cancer worldwide and one of the major causes of cancer death in women. Epidemiological studies have established a link between night-shift work and increased cancer risk, suggesting that circadian disruption may play a role in carcinogenesis. Here, we aim to shed light on the effect of chronic jetlag (JL) on mammary tumour development. To do this, we use a mouse model of spontaneous mammary tumourigenesis and subject it to chronic circadian disruption. We...
The circadian clock controls most of the physiological processes in the body throughout days and nights' alternation. Its dysregulation has a negative impact on many aspects of human health, such as obesity, lipid disorders, diabetes, skin regeneration, hematopoiesis and cancer. To date, poor is known on the molecular mechanisms that links mammary gland homeostasis to the circadian clock but recent reports highlight the importance of loss of circadian genes for mammary gland development and...