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2. Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome

Author

Barry, Alexandra, McNulty, Michelle T., Jia, Xiaoyuan, Gupta, Yask, Debiec, Hanna, Luo, Yang, Nagano, China, Horinouchi, Tomoko, Jung, Seulgi, Colucci, Manuela, Ahram, Dina F., Mitrotti, Adele, Sinha, Aditi, Teeninga, Nynke, Jin, Gina, Shril, Shirlee, Caridi, Gianluca, Bodria, Monica, Lim, Tze Y., Westland, Rik, Zanoni, Francesca, Marasa, Maddalena, Turudic, Daniel, Giordano, Mario, Gesualdo, Loreto, Magistroni, Riccardo, Pisani, Isabella, Fiaccadori, Enrico, Reiterova, Jana, Maringhini, Silvio, Morello, William, Montini, Giovanni, Weng, Patricia L., Scolari, Francesco, Saraga, Marijan, Tasic, Velibor, Santoro, Domenica, van Wijk, Joanna A. E., Milošević, Danko, Kawai, Yosuke, Kiryluk, Krzysztof, Pollak, Martin R., Gharavi, Ali, Lin, Fangmin, Simœs e Silva, Ana Cristina, Loos, Ruth J. F., Kenny, Eimear E., Schreuder, Michiel F., Zurowska, Aleksandra, Dossier, Claire, Ariceta, Gema, Drozynska-Duklas, Magdalena, Hogan, Julien, Jankauskiene, Augustina, Hildebrandt, Friedhelm, Prikhodina, Larisa, Song, Kyuyoung, Bagga, Arvind, Cheong, II, Hae, Ghiggeri, Gian Marco, Vachvanichsanong, Prayong, Nozu, Kandai, Lee, Dongwon, Vivarelli, Marina, Raychaudhuri, Soumya, Tokunaga, Katsushi, Sanna-Cherchi, Simone, Ronco, Pierre, Iijima, Kazumoto, and Sampson, Matthew G.

Published
2023
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4. PTEN inhibits AMPK to control collective migration

Author

Florent Peglion, Lavinia Capuana, Isabelle Perfettini, Laurent Boucontet, Ben Braithwaite, Emma Colucci-Guyon, Emie Quissac, Karin Forsberg-Nilsson, Flora Llense, and Sandrine Etienne-Manneville

Subjects
Science
Abstract

Pten is a tumour suppressor gene that is associated with highly invasive cancers such as glioblastoma. Here the authors show that PTEN loss results in increased migratory behaviour, which can be countered by targeting AMPK activity.

Published
2022
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7. Distinctive phenotypes and functions of innate lymphoid cells in human decidua during early pregnancy

Author

Oisín Huhn, Martin A. Ivarsson, Lucy Gardner, Mike Hollinshead, Jane C Stinchcombe, Puran Chen, Norman Shreeve, Olympe Chazara, Lydia E. Farrell, Jakob Theorell, Hormas Ghadially, Peter Parham, Gillian Griffiths, Amir Horowitz, Ashley Moffett, Andrew M. Sharkey, and Francesco Colucci

Subjects
Science
Abstract

As an interface between maternal and fetal tissues, decidua hosts immune cells specialized in fostering a successful pregnancy. Here the authors carry out high-dimensional characterization of function, morphology and surface markers of human decidual innate lymphoid cells (ILCs), identifying subsets with features distinct from blood ILC.

Published
2020
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8. Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells

Author

Claudia Burrello, Federica Garavaglia, Fulvia Milena Cribiù, Giulia Ercoli, Gianluca Lopez, Jacopo Troisi, Angelo Colucci, Silvia Guglietta, Sara Carloni, Simone Guglielmetti, Valentina Taverniti, Giulia Nizzoli, Silvano Bosari, Flavio Caprioli, Maria Rescigno, and Federica Facciotti

Subjects
Science
Abstract

Faecal microbiota transplantation (FMT) is becoming a therapeutic option in several gastrointestinal disorders. Here, Burrello et al. study the immunological mechanisms by which FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis in a mouse model of colitis.

Published
2018
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9. Molecular definition of group 1 innate lymphoid cells in the mouse uterus

Author

Iva Filipovic, Laura Chiossone, Paola Vacca, Russell S. Hamilton, Tiziano Ingegnere, Jean-Marc Doisne, Delia A. Hawkes, Maria Cristina Mingari, Andrew M. Sharkey, Lorenzo Moretta, and Francesco Colucci

Subjects
Science
Abstract

Studying the uterine lymphocyte pool is difficult due to its dynamic nature induced by various pregnancy-related factors. Here the authors provide, using transcriptome data from sorted mouse group 1 innate lymphoid cells (ILC), a molecular atlas of these cells, which implicates tissue-resident natural killer cells as a hub for uterine immune crosstalk.

Published
2018
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10. Cysteine-mediated decyanation of vitamin B12 by the predicted membrane transporter BtuM

Author

S. Rempel, E. Colucci, J. W. de Gier, A. Guskov, and D. J. Slotboom

Subjects
Science
Abstract

Uptake of vitamin B12 is essential for many prokaryotes, but in most cases the membrane proteins involved are yet to be identified. Here, the authors use X-ray crystallography and spectroscopy to characterize BtuM, a predicted bacterial substrate-modifying vitamin B12 transporter.

Published
2018
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12. Decidualisation and placentation defects are a major cause of age-related reproductive decline

Author

Laura Woods, Vicente Perez-Garcia, Jens Kieckbusch, Xiaoqiu Wang, Francesco DeMayo, Francesco Colucci, and Myriam Hemberger

Subjects
Science
Abstract

Advanced maternal age has been associated with lower reproductive success and higher risk of pregnancy complications. Here the authors show that maternal ageing-related embryonic abnormalities in mouse are caused by decidualisation and placentation defects that can be rescued by transferring the embryo from an old to a young uterus.

Published
2017
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16. Correction: Corrigendum: MHC-dependent inhibition of uterine NK cells impedes fetal growth and decidual vascular remodeling

Author

Jens Kieckbusch, Louise M. Gaynor, Ashley Moffett, and Francesco Colucci

Subjects
Science
Abstract

Nature Communications 5: Article number: 3359 (2014); Published: 28 February 2014; Updated: 20 April 2017 This Article was originally published under a CC BY-NC-ND 3.0 license, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.

Published
2017
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17. Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome

Author

Alexandra Barry, Michelle T. McNulty, Xiaoyuan Jia, Yask Gupta, Hanna Debiec, Yang Luo, China Nagano, Tomoko Horinouchi, Seulgi Jung, Manuela Colucci, Dina F. Ahram, Adele Mitrotti, Aditi Sinha, Nynke Teeninga, Gina Jin, Shirlee Shril, Gianluca Caridi, Monica Bodria, Tze Y. Lim, Rik Westland, Francesca Zanoni, Maddalena Marasa, Daniel Turudic, Mario Giordano, Loreto Gesualdo, Riccardo Magistroni, Isabella Pisani, Enrico Fiaccadori, Jana Reiterova, Silvio Maringhini, William Morello, Giovanni Montini, Patricia L. Weng, Francesco Scolari, Marijan Saraga, Velibor Tasic, Domenica Santoro, Joanna A. E. van Wijk, Danko Milošević, Yosuke Kawai, Krzysztof Kiryluk, Martin R. Pollak, Ali Gharavi, Fangmin Lin, Ana Cristina Simœs e Silva, Ruth J. F. Loos, Eimear E. Kenny, Michiel F. Schreuder, Aleksandra Zurowska, Claire Dossier, Gema Ariceta, Magdalena Drozynska-Duklas, Julien Hogan, Augustina Jankauskiene, Friedhelm Hildebrandt, Larisa Prikhodina, Kyuyoung Song, Arvind Bagga, Hae Cheong, Gian Marco Ghiggeri, Prayong Vachvanichsanong, Kandai Nozu, Dongwon Lee, Marina Vivarelli, Soumya Raychaudhuri, Katsushi Tokunaga, Simone Sanna-Cherchi, Pierre Ronco, Kazumoto Iijima, and Matthew G. Sampson

Subjects
Science
Abstract

Abstract Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations—eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.

Published
2023
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18. Mutation in glutamate transporter homologue GltTk provides insights into pathologic mechanism of episodic ataxia 6

Author

Emanuela Colucci, Zaid R. Anshari, Miyer F. Patiño-Ruiz, Mariia Nemchinova, Jacob Whittaker, Dirk J. Slotboom, and Albert Guskov

Subjects
Science
Abstract

Episodic ataxias (EAs) are rare neurological conditions that cause motor impairment. Here the authors investigated the molecular mechanism of such a pathological condition caused by a mutation of a conserved proline into arginine residue.

Published
2023
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19. Single-cell transcriptomics identifies Mcl-1 as a target for senolytic therapy in cancer

Author

Martina Troiani, Manuel Colucci, Mariantonietta D’Ambrosio, Ilaria Guccini, Emiliano Pasquini, Angelica Varesi, Aurora Valdata, Simone Mosole, Ajinkya Revandkar, Giuseppe Attanasio, Andrea Rinaldi, Anna Rinaldi, Marco Bolis, Pietro Cippà, and Andrea Alimonti

Subjects
Science
Abstract

Abstract Cells subjected to treatment with anti-cancer therapies can evade apoptosis through cellular senescence. Persistent senescent tumor cells remain metabolically active, possess a secretory phenotype, and can promote tumor proliferation and metastatic dissemination. Removal of senescent tumor cells (senolytic therapy) has therefore emerged as a promising therapeutic strategy. Here, using single-cell RNA-sequencing, we find that senescent tumor cells rely on the anti-apoptotic gene Mcl-1 for their survival. Mcl-1 is upregulated in senescent tumor cells, including cells expressing low levels of Bcl-2, an established target for senolytic therapy. While treatment with the Bcl-2 inhibitor Navitoclax results in the reduction of metastases in tumor bearing mice, treatment with the Mcl-1 inhibitor S63845 leads to complete elimination of senescent tumor cells and metastases. These findings provide insights on the mechanism by which senescent tumor cells survive and reveal a vulnerability that can be exploited for cancer therapy.

Published
2022
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