Vizgen, MEng, MBA, Regional Account Manager
contact : Laurent Le Cam (Inserm)
Biological systems are composed of numerous cell types, intricately organized to form functional tissues and organs. While recent advancements in genomics technologies have made it possible to characterize cell types through careful analysis of the transcriptome, they are unable to resolve how gene expression and cell types are spatially arranged. In this presentation, we introduce you to Vizgen’s all-in-one in situ genomics platform MERSCOPE, which enables the direct profiling of the spatial organization of intact tissue with genomic scale
throughput. The instrument, the MERFISH chemistry and use cases will be presented as well.
Institut Gustave Roussy (IGR)-Paris
contact Julie Constanzo (ICM)
Florent Ginhoux is graduated in Biochemistry from the University Pierre et Marie CURIE (UPMC), Paris VI, obtained a Masters degree in Immunology from the Pasteur Institute in 2000 and his PhD in 2004 from UPMC, Paris VI. As a postdoctoral fellow, he joined the Laboratory of Miriam Merad in the Mount Sinai School of Medicine (MSSM), New York, where he studied the ontogeny and the homeostasis of cutaneous dendritic cell populations, with a strong focus on Langerhans cells and Microglia. In 2008, he became an Assistant Professor in the Department of Gene and Cell Medicine, MSSM and member of the Immunology Institute of MSSM. He joined the Singapore Immunology Network (SIgN), A*STAR in May 2009 as a Junior Principal Investigator and became Senior Principal Investigator in 2014. He joined the EMBO Young Investigator (YIP) program in 2013 and is a Web of Science Highly Cited Researcher since 2016. He is also an Adjunct Visiting Associate Professor in the Shanghai Immunology Institute, Jiao Tong University, in Shanghai, China since 2015 and Adjunct Associate Professor in the Translational Immunology Institute, SingHealth and Duke NUS, Singapore since 2016. He is now a Laboratory Director in Gustave Roussy focusing on pediatric cancers and the role of myeloid cells in tumor progression and became an EMBO member in 2022.
Associate Professor in Genetics @Biotech, AUA & Head of Dark DNA group
Medical School of Athens University, Greece
contact : Andrei TURTOI (Inserm)
Why is so hard to design or discover a new drug nowadays? Is it because all the “easy” ones have been discovered? Is it because new regulations for taking a new candidate drug through clinical trials are too strict? It is because it is so time consuming and very expensive business indeed? Or is it just that the tools that have been used in this field are outdated and need to be refreshed? In this direction, novel Artificial Intelligence and Machine Learning pipelines are being designed by the merging of a repertoire of different scientific disciplines. Medicinal chemistry meets informatics, mathematics, biology, translational medicine, genetics and big data science and the result is simply amazing and very promising! There is new hope for drugs for cancer, autoimmune diseases, neurodegenerative diseases, inflammation and even rare diseases under the prism of precision medicine. Those new techniques and recent major scientific breakthroughs pave the way towards the development and establishment of the novel holistic drug design stratagems of tomorrow. However, even though it is clear that teaching an old dog new tricks is possible, it looks like it may not happen overnight.
Centre de Recherche des Cordeliers, INSERM UMRS1138, Paris
contact : Florence Cammas (Inserm/CNRS)
Genetic and Epigenetic control of normal and malignant hematopoiesis
Institut de Recherche Saint Louis / INSERM U944 / CNRS UMR7212
contact : Antonio Maraver (IRCM-Inserm)
Acute myeloid leukemia (AML) is a type of cancer that affects the blood and bone marrow. It is characterized by the overproduction of immature white blood cells, called myeloblasts, which can crowd out healthy blood cells and lead to a variety of symptoms, including fatigue, infection, and bleeding. AML is the most common acute leukemia diagnosed in adult and has a high relapse rate with a dismal overall 5-year survival of 24%. AML is a complex disease that is driven by a variety of genetic and epigenetic changes but its exact causes are still not fully understood.
Enhancers are non-coding regions of DNA that play a crucial role in regulating gene expression. They act as binding sites for transcription factors to promote gene transcription. Super-enhancers are clusters of enhancers that are characterized by a high density of transcription factor binding sites. They have been characterized as a particular class of enhancers controlling cell type specific gene expression programs and tend to be enriched around and control oncogenes. In leukemia, enhancers have been shown to be key players in the development and progression of the disease. Identification of the direct functional and physical relationship between Super-Enhancers and their target oncogenes could help decipher complex coordinated gene expression programs that lead to leukemogenesis. Study of the dynamic interplay between enhancers, and gene expression program could unravel novel collaborative oncogenic mechanisms and help design more effective combinatorial therapies.
In a recent study we hypothesized that important regulatory regions such as Super-Enhancers could control simultaneously expression of genes cooperating in functional modules to promote leukemia development. To identify key Super-Enhancers that are involved in AML cell growth and survival, we used a screening methodology called CRISPRi, which relies on the use of a deactivated Cas9 protein fused to a KRAB domain to target and inactivate Super-Enhancers. We deployed this strategy in the ETO2-GLIS2 fusion driven model of acute megakaryoblastic leukemia (AMKL), an aggressive pediatric myeloid leukemia with poor prognosis, which mainly relies on the ETO2-GLIS2 as the transforming lesion. Among the top hits of our screen, we identified a novel Super-Enhancer, located 5’ to the KIT gene on chromosome 4. We found that it directly interacts and regulates the expression of KIT and PDGFRA genes, which are both required for leukemia progression in vitro and in vivo. These results suggest that Super-Enhancers could control simultaneously the expression of genes cooperating in functional modules to promote leukemia development.
Our findings provide new insights into the molecular mechanisms underlying AML pathogenesis and highlight the importance of understanding the role of enhancers and Super-Enhancers in the development and progression of leukemias. We believe that systematic screening of essential Super-Enhancers can reveal coordinated regulation of genes involved in cancer cell transformation and cancer progression and could help to uncover novel therapeutic approaches.
Director of Research Inserm - Laboratoire CRIBL ( Contrôle de la Réponse Immune B et Lymphoproliférations) - UMR CNRS 7276 - Inserm U1262 à l'Université de Limoges
Abstract : "FasL belongs to the TNF family and interacts with the “so-called” death receptor Fas to trigger apoptosis. FasL is a transmembrane ligand, which can be cleaved by metalloproteases to release a soluble factor. While the membrane-bound FasL is a potent inducer of apoptosis, its soluble counterpart fails to induce cell death but trigger pro-inflammatory signals promoting the migration of triple negative breast cancer cells. More recently, we found that the loss of Fas in TNBC cells engenders a potent pro-inflammatory NF-kB signaling pathway, which promotes the elimination of the cancer cells via the activation/recruitment of anti-tumor NK cells. Because Fas expression is maintained in breast cancer cells isolated from TNBC patients and is associated with a good prognosis, we now aim at identifying in a comprehensive manner the Fas-dependent molecular mechanism controlling NF-kB in these TNBC cells."
Contact : Nathalie Bonnefoy