Accueil
L'unité en quelques chiffres clés :
 Créé en 2022 |
 82 membres |
 5 équipes de recherche |
 227 publications (2015-2023) |
 42 soutenances de thèse (2015-2023) |
Les équipes :
Publications récentes :
Pu, Yi; Li, Lu; Peng, Haoning; Liu, Lunxu; Heymann, Dominique; Robert, Caroline; Vallette, François; Shen, Shensi
Drug-tolerant persister cells in cancer: the cutting edges and future directions Article de journal
Dans: Nature Reviews Clinical Oncology, 2023, ISSN: 1759-4782.
@article{pu_drug-tolerant_2023,
title = {Drug-tolerant persister cells in cancer: the cutting edges and future directions},
author = {Yi Pu and Lu Li and Haoning Peng and Lunxu Liu and Dominique Heymann and Caroline Robert and François Vallette and Shensi Shen},
url = {https://doi.org/10.1038/s41571-023-00815-5},
doi = {10.1038/s41571-023-00815-5},
issn = {1759-4782},
year = {2023},
date = {2023-09-01},
urldate = {2023-09-01},
journal = {Nature Reviews Clinical Oncology},
abstract = {Drug-tolerant persister (DTP) cell populations were originally discovered in antibiotic-resistant bacterial biofilms. Similar populations with comparable features have since been identified among cancer cells and have been linked with treatment resistance that lacks an underlying genomic alteration. Research over the past decade has improved our understanding of the biological roles of DTP cells in cancer, although clinical knowledge of the role of these cells in treatment resistance remains limited. Nonetheless, targeting this population is anticipated to provide new treatment opportunities. In this Perspective, we aim to provide a clear definition of the DTP phenotype, discuss the underlying characteristics of these cells, their biomarkers and vulnerabilities, and encourage further research on DTP cells that might improve our understanding and enable the development of more effective anticancer therapies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Drug-tolerant persister (DTP) cell populations were originally discovered in antibiotic-resistant bacterial biofilms. Similar populations with comparable features have since been identified among cancer cells and have been linked with treatment resistance that lacks an underlying genomic alteration. Research over the past decade has improved our understanding of the biological roles of DTP cells in cancer, although clinical knowledge of the role of these cells in treatment resistance remains limited. Nonetheless, targeting this population is anticipated to provide new treatment opportunities. In this Perspective, we aim to provide a clear definition of the DTP phenotype, discuss the underlying characteristics of these cells, their biomarkers and vulnerabilities, and encourage further research on DTP cells that might improve our understanding and enable the development of more effective anticancer therapies.
Lailheugue, Vincent; Merlin, Isabelle; Boutet, Stéphanie; Perreau, François; Pouvreau, Jean-Bernard; Delgrange, Sabine; Ducrot, Paul-Henri; Cottyn-Boitte, Betty; Mouille, Gregory; Lauvergeat, Virginie
Vitislactone, a non-canonical strigolactone exudated by grapevine rootstocks in response to nitrogen starvation Article de journal
Dans: Phytochemistry, vol. 215, p. 113837, 2023, ISSN: 1873-3700.
@article{pmid37640279,
title = {Vitislactone, a non-canonical strigolactone exudated by grapevine rootstocks in response to nitrogen starvation},
author = {Vincent Lailheugue and Isabelle Merlin and Stéphanie Boutet and François Perreau and Jean-Bernard Pouvreau and Sabine Delgrange and Paul-Henri Ducrot and Betty Cottyn-Boitte and Gregory Mouille and Virginie Lauvergeat},
doi = {10.1016/j.phytochem.2023.113837},
issn = {1873-3700},
year = {2023},
date = {2023-08-01},
urldate = {2023-08-01},
journal = {Phytochemistry},
volume = {215},
pages = {113837},
abstract = {Strigolactones are compounds produced by plant roots in response to nutrient deficiency, acting both as local and systemic signals to control development and nutrition. Strigolactones are exuded in the rhizosphere to positively influence interactions with beneficial microbes. LC-MS/MS analysis shows that two genetically distinct grapevine rootstocks exudate one or two non-canonical strigolactones when subjected to low nitrogen conditions. Gene expression profiles and orobanche seed germination assays confirm that the biosynthesis and exudation of non-canonical compounds is the preferred pathway. The first compound, corresponding to heliolactone or 6-epi-heliolactone, is only exuded by the rootstock showing lower shoot branching and a higher level of mycorrhization with arbuscular mycorrhizal fungi. The structure of the second compound exuded by both rootstocks was identified by NMR and LC-MS/MS analysis. It is a non-canonical strigolactone, which has never been identified in another species. This first identification of a natural compound with the potential to stimulate beneficial root-microbe interactions in grapevines opens new perspectives in viticulture.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Strigolactones are compounds produced by plant roots in response to nutrient deficiency, acting both as local and systemic signals to control development and nutrition. Strigolactones are exuded in the rhizosphere to positively influence interactions with beneficial microbes. LC-MS/MS analysis shows that two genetically distinct grapevine rootstocks exudate one or two non-canonical strigolactones when subjected to low nitrogen conditions. Gene expression profiles and orobanche seed germination assays confirm that the biosynthesis and exudation of non-canonical compounds is the preferred pathway. The first compound, corresponding to heliolactone or 6-epi-heliolactone, is only exuded by the rootstock showing lower shoot branching and a higher level of mycorrhization with arbuscular mycorrhizal fungi. The structure of the second compound exuded by both rootstocks was identified by NMR and LC-MS/MS analysis. It is a non-canonical strigolactone, which has never been identified in another species. This first identification of a natural compound with the potential to stimulate beneficial root-microbe interactions in grapevines opens new perspectives in viticulture.
Panez-Toro, Isidora; Muñoz-García, Javier; Vargas-Franco, Jorge W.; Renodon-Cornière, Axelle; Heymann, Marie-Françoise; Lézot, Frédéric; Heymann, Dominique
Advances in Osteosarcoma Article de journal
Dans: Current Osteoporosis Reports, 2023, ISSN: 1544-1873, 1544-2241.
@article{panez-toro_advances_2023,
title = {Advances in Osteosarcoma},
author = {Isidora Panez-Toro and Javier Muñoz-García and Jorge W. Vargas-Franco and Axelle Renodon-Cornière and Marie-Françoise Heymann and Frédéric Lézot and Dominique Heymann},
url = {https://link.springer.com/10.1007/s11914-023-00803-9},
doi = {10.1007/s11914-023-00803-9},
issn = {1544-1873, 1544-2241},
year = {2023},
date = {2023-06-01},
urldate = {2023-06-01},
journal = {Current Osteoporosis Reports},
abstract = {Purpose of Review
This article gives a brief overview of the most recent developments in osteosarcoma treatment, including targeting of signaling pathways, immune checkpoint inhibitors, drug delivery strategies as single or combined approaches, and the identification of new therapeutic targets to face this highly heterogeneous disease.
Recent Findings
Osteosarcoma is one of the most common primary malignant bone tumors in children and young adults, with a high risk of bone and lung metastases and a 5-year survival rate around 70% in the absence of metastases and 30% if metastases are detected at the time of diagnosis. Despite the novel advances in neoadjuvant chemotherapy, the effective treatment for osteosarcoma has not improved in the last 4 decades. The emergence of immunotherapy has transformed the paradigm of treatment, focusing therapeutic strategies on the potential of immune checkpoint inhibitors. However, the most recent clinical trials show a slight improvement over the conventional polychemotherapy scheme.
Summary
The tumor microenvironment plays a crucial role in the pathogenesis of osteosarcoma by controlling the tumor growth, the metastatic process and the drug resistance and paved the way of new therapeutic options that must be validated by accurate pre-clinical studies and clinical trials.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Purpose of Review
This article gives a brief overview of the most recent developments in osteosarcoma treatment, including targeting of signaling pathways, immune checkpoint inhibitors, drug delivery strategies as single or combined approaches, and the identification of new therapeutic targets to face this highly heterogeneous disease.
Recent Findings
Osteosarcoma is one of the most common primary malignant bone tumors in children and young adults, with a high risk of bone and lung metastases and a 5-year survival rate around 70% in the absence of metastases and 30% if metastases are detected at the time of diagnosis. Despite the novel advances in neoadjuvant chemotherapy, the effective treatment for osteosarcoma has not improved in the last 4 decades. The emergence of immunotherapy has transformed the paradigm of treatment, focusing therapeutic strategies on the potential of immune checkpoint inhibitors. However, the most recent clinical trials show a slight improvement over the conventional polychemotherapy scheme.
Summary
The tumor microenvironment plays a crucial role in the pathogenesis of osteosarcoma by controlling the tumor growth, the metastatic process and the drug resistance and paved the way of new therapeutic options that must be validated by accurate pre-clinical studies and clinical trials.
This article gives a brief overview of the most recent developments in osteosarcoma treatment, including targeting of signaling pathways, immune checkpoint inhibitors, drug delivery strategies as single or combined approaches, and the identification of new therapeutic targets to face this highly heterogeneous disease.
Recent Findings
Osteosarcoma is one of the most common primary malignant bone tumors in children and young adults, with a high risk of bone and lung metastases and a 5-year survival rate around 70% in the absence of metastases and 30% if metastases are detected at the time of diagnosis. Despite the novel advances in neoadjuvant chemotherapy, the effective treatment for osteosarcoma has not improved in the last 4 decades. The emergence of immunotherapy has transformed the paradigm of treatment, focusing therapeutic strategies on the potential of immune checkpoint inhibitors. However, the most recent clinical trials show a slight improvement over the conventional polychemotherapy scheme.
Summary
The tumor microenvironment plays a crucial role in the pathogenesis of osteosarcoma by controlling the tumor growth, the metastatic process and the drug resistance and paved the way of new therapeutic options that must be validated by accurate pre-clinical studies and clinical trials.
Loussouarn, Delphine; Oliver, Lisa; Salaud, Celine; Samarut, Edouard; Bourgade, Raphaël; Béroud, Christophe; Morenton, Emilie; Heymann, Dominique; Vallette, Francois M.
Spatial Distribution of Immune Cells in Primary and Recurrent Glioblastoma: A Small Case Study Article de journal
Dans: Cancers, vol. 15, no. 12, p. 3256, 2023, ISSN: 2072-6694.
@article{loussouarn_spatial_2023,
title = {Spatial Distribution of Immune Cells in Primary and Recurrent Glioblastoma: A Small Case Study},
author = {Delphine Loussouarn and Lisa Oliver and Celine Salaud and Edouard Samarut and Raphaël Bourgade and Christophe Béroud and Emilie Morenton and Dominique Heymann and Francois M. Vallette},
url = {https://www.mdpi.com/2072-6694/15/12/3256},
doi = {10.3390/cancers15123256},
issn = {2072-6694},
year = {2023},
date = {2023-06-01},
urldate = {2023-06-01},
journal = {Cancers},
volume = {15},
number = {12},
pages = {3256},
abstract = {Only a minority of patients with glioblastoma (GBM) respond to immunotherapy, and always only partially. There is a lack of knowledge on immune distribution in GBM and in its tumor microenvironment (TME). To address the question, we used paired primary and recurrent tumors from GBM patients to study the composition and the evolution of the immune landscape upon treatment. We studied the expression of a handful of immune markers (CD3, CD8, CD68, PD-L1 and PD-1) in GBM tissues in 15 paired primary and recurrent GBM. In five selected patients, we used Nanostring Digital Spatial Profiling (DSP) to obtain simultaneous assessments of multiple biomarkers both within the tumor and the microenvironment in paired primary and recurrent GBM. Our results suggest that the evolution of the immune landscape between paired primary and recurrent GBM tumors is highly heterogeneous. However, our study identifies B3-H7 and HLA-DR as potential targets in primary and recurrent GBM. Spatial profiling of immune markers from matched primary and recurrent GBM shows a nonlinear complex evolution during the progression of cancer. Nonetheless, our study demonstrated a global increase in macrophages, and revealed differential localization of some markers, such as B7-H3 and HLA-DR, between GBM and its TME.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Only a minority of patients with glioblastoma (GBM) respond to immunotherapy, and always only partially. There is a lack of knowledge on immune distribution in GBM and in its tumor microenvironment (TME). To address the question, we used paired primary and recurrent tumors from GBM patients to study the composition and the evolution of the immune landscape upon treatment. We studied the expression of a handful of immune markers (CD3, CD8, CD68, PD-L1 and PD-1) in GBM tissues in 15 paired primary and recurrent GBM. In five selected patients, we used Nanostring Digital Spatial Profiling (DSP) to obtain simultaneous assessments of multiple biomarkers both within the tumor and the microenvironment in paired primary and recurrent GBM. Our results suggest that the evolution of the immune landscape between paired primary and recurrent GBM tumors is highly heterogeneous. However, our study identifies B3-H7 and HLA-DR as potential targets in primary and recurrent GBM. Spatial profiling of immune markers from matched primary and recurrent GBM shows a nonlinear complex evolution during the progression of cancer. Nonetheless, our study demonstrated a global increase in macrophages, and revealed differential localization of some markers, such as B7-H3 and HLA-DR, between GBM and its TME.
Mauro, E; Lapaillerie, D; Tumiotto, C; Charlier, C; Martins, F; Sousa, S F; Métifiot, M; Weigel, P; Yamatsugu, K; Kanai, M; Munier-Lehmann, H; Richetta, C; Maisch, M; Dutrieux, J; Batisse, J; Ruff, M; Delelis, O; Lesbats, P; Parissi, V
Modulation of the functional interfaces between retroviral intasomes and the human nucleosome Article de journal
Dans: mBio, p. e0108323, 2023, ISSN: 2150-7511.
@article{pmid37382440,
title = {Modulation of the functional interfaces between retroviral intasomes and the human nucleosome},
author = {E Mauro and D Lapaillerie and C Tumiotto and C Charlier and F Martins and S F Sousa and M Métifiot and P Weigel and K Yamatsugu and M Kanai and H Munier-Lehmann and C Richetta and M Maisch and J Dutrieux and J Batisse and M Ruff and O Delelis and P Lesbats and V Parissi},
doi = {10.1128/mbio.01083-23},
issn = {2150-7511},
year = {2023},
date = {2023-06-01},
urldate = {2023-06-01},
journal = {mBio},
pages = {e0108323},
abstract = {Infection by retroviruses as HIV-1 requires the stable integration of their genome into the host cells. This process needs the formation of integrase (IN)-viral DNA complexes, called intasomes, and their interaction with the target DNA wrapped around nucleosomes within cell chromatin. To provide new tools to analyze this association and select drugs, we applied the AlphaLISA technology to the complex formed between the prototype foamy virus (PFV) intasome and nucleosome reconstituted on 601 Widom sequence. This system allowed us to monitor the association between both partners and select small molecules that could modulate the intasome/nucleosome association. Using this approach, drugs acting either on the DNA topology within the nucleosome or on the IN/histone tail interactions have been selected. Within these compounds, doxorubicin and histone binders calixarenes were characterized using biochemical, molecular simulations and cellular approaches. These drugs were shown to inhibit both PFV and HIV-1 integration . Treatment of HIV-1-infected PBMCs with the selected molecules induces a decrease in viral infectivity and blocks the integration process. Thus, in addition to providing new information about intasome-nucleosome interaction determinants, our work also paves the way for further unedited antiviral strategies that target the final step of intasome/chromatin anchoring. IMPORTANCE In this work, we report the first monitoring of retroviral intasome/nucleosome interaction by AlphaLISA. This is the first description of the AlphaLISA application for large nucleoprotein complexes (>200 kDa) proving that this technology is suitable for molecular characterization and bimolecular inhibitor screening assays using such large complexes. Using this system, we have identified new drugs disrupting or preventing the intasome/nucleosome complex and inhibiting HIV-1 integration both and in infected cells. This first monitoring of the retroviral/intasome complex should allow the development of multiple applications including the analyses of the influence of cellular partners, the study of additional retroviral intasomes, and the determination of specific interfaces. Our work also provides the technical bases for the screening of larger libraries of drugs targeting specifically these functional nucleoprotein complexes, or additional nucleosome-partner complexes, as well as for their characterization.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Infection by retroviruses as HIV-1 requires the stable integration of their genome into the host cells. This process needs the formation of integrase (IN)-viral DNA complexes, called intasomes, and their interaction with the target DNA wrapped around nucleosomes within cell chromatin. To provide new tools to analyze this association and select drugs, we applied the AlphaLISA technology to the complex formed between the prototype foamy virus (PFV) intasome and nucleosome reconstituted on 601 Widom sequence. This system allowed us to monitor the association between both partners and select small molecules that could modulate the intasome/nucleosome association. Using this approach, drugs acting either on the DNA topology within the nucleosome or on the IN/histone tail interactions have been selected. Within these compounds, doxorubicin and histone binders calixarenes were characterized using biochemical, molecular simulations and cellular approaches. These drugs were shown to inhibit both PFV and HIV-1 integration . Treatment of HIV-1-infected PBMCs with the selected molecules induces a decrease in viral infectivity and blocks the integration process. Thus, in addition to providing new information about intasome-nucleosome interaction determinants, our work also paves the way for further unedited antiviral strategies that target the final step of intasome/chromatin anchoring. IMPORTANCE In this work, we report the first monitoring of retroviral intasome/nucleosome interaction by AlphaLISA. This is the first description of the AlphaLISA application for large nucleoprotein complexes (>200 kDa) proving that this technology is suitable for molecular characterization and bimolecular inhibitor screening assays using such large complexes. Using this system, we have identified new drugs disrupting or preventing the intasome/nucleosome complex and inhibiting HIV-1 integration both and in infected cells. This first monitoring of the retroviral/intasome complex should allow the development of multiple applications including the analyses of the influence of cellular partners, the study of additional retroviral intasomes, and the determination of specific interfaces. Our work also provides the technical bases for the screening of larger libraries of drugs targeting specifically these functional nucleoprotein complexes, or additional nucleosome-partner complexes, as well as for their characterization.