Imperial College London

ProfessorLucaMagnani

Faculty of MedicineDepartment of Surgery & Cancer

Chair in Cancer Adaptation and Evolution
 
 
 
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Contact

 

+44 (0)20 7594 2808l.magnani CV

 
 
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Location

 

137ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

86 results found

Magnani L, Lee K, Fodor WL, Machaty Z, Cabot RAet al., 2008, Developmental capacity of porcine nuclear transfer embryos correlate with levels of chromatin-remodeling transcripts in donor cells, MOLECULAR REPRODUCTION AND DEVELOPMENT, Vol: 75, Pages: 766-776, ISSN: 1040-452X

Journal article

Magnani L, Cabot R, 2008, Relative abundance of Oct-4, Nanog, and Sox-2 transcripts in porcine oocytes and cleavage-stage embryos produced via fertilization in vitro or parthenogenesis, REPRODUCTION FERTILITY AND DEVELOPMENT, Vol: 20, Pages: 168-169, ISSN: 1031-3613

Journal article

Magnani L, Johnson CM, Cabot RA, 2008, Expression of eukaryotic elongation initiation factor 1A differentially marks zygotic genome activation in biparental and parthenogenetic porcine embryos and correlates with in vitro developmental potential, REPRODUCTION FERTILITY AND DEVELOPMENT, Vol: 20, Pages: 818-825, ISSN: 1031-3613

Journal article

Park K, Magnani L, Cabot R, 2008, Expression patterns of H3/K27 methylation mediating genes in porcine embryos, 41st Annual Meeting of the Society-for-the-Study-of-Reproduction, Publisher: SOC STUDY REPRODUCTION, Pages: 96-97, ISSN: 0006-3363

Conference paper

Magnani L, Cabot R, 2008, Ectopic expression of Brahma in porcine embryos induces developmental arrest and alters expression of SNF2L, 41st Annual Meeting of the Society-for-the-Study-of-Reproduction, Publisher: SOC STUDY REPRODUCTION, Pages: 72-72, ISSN: 0006-3363

Conference paper

Magnani L, Cabot RA, 2007, Developmental arrest induced in cleavage stage porcine embryos following microinjection of mRNA encoding Brahma (Smarca 2), a chromatin remodeling protein, MOLECULAR REPRODUCTION AND DEVELOPMENT, Vol: 74, Pages: 1262-1267, ISSN: 1040-452X

Journal article

Carli B, Bazzini G, Castelli E, Cecchi-Pestellini C, Del Bianco S, Dinelli BM, Gai M, Magnani L, Ridolfi M, Santurri Let al., 2007, MARC: A code for the retrieval of atmospheric parameters from millimeter-wave limb measurements, JOURNAL OF QUANTITATIVE SPECTROSCOPY & RADIATIVE TRANSFER, Vol: 105, Pages: 476-491, ISSN: 0022-4073

Journal article

Biancardi M, Cabot R, Magnani L, 2007, The histone methyltransferase G9A adopts a nuclear localization in cleaved porcine embryos, but rarely in pronuclear stage embryos., 40th Annual Meeting of the Society-for-the-Study-of-Reproduction, Publisher: SOC STUDY REPRODUCTION, Pages: 89-89, ISSN: 0006-3363

Conference paper

Johnson C, Magnani L, Cabot R, 2007, Histone methyltransferase glp shows reduced amount of transcript from the GV-stage oocyte to the 8-cell stage in porcine parthenogenetic embryos., 40th Annual Meeting of the Society-for-the-Study-of-Reproduction, Publisher: SOC STUDY REPRODUCTION, Pages: 113-113, ISSN: 0006-3363

Conference paper

Dinelli BM, Arnone E, Brizzi G, Carlotti M, Magnani L, Papandrea E, Ridolfi Met al., 2006, The DCFI-ISAC MIPAS database: 2-D routine analysis of MIPAS observations, ISSN: 0379-6566

The measurements of MIPAS/ENVISAT, in its original nominal observation mode, are analyzed with the GMTR retrieval system in order to obtain 2-D fields of pressure, temperature and Volume Mixing Ratio of H2O, O 3, HNO3, CH4, N2O and NO 2. The MIPAS level-1b data are archived in the disks cluster of the MIPAS Bologna Facility. The GMTR analysis system, developed in the frame of an ESA supported study, is distributed as part of the BEAT tools. Samples of the obtained results are presented and compared with the corresponding ESA Level 2 MIPAS products.

Conference paper

Carlotti M, Brizzi G, Papandrea E, Prevedelli M, Ridolfi M, Dinelli BM, Magnani Let al., 2006, GMTR: Two-dimensional geo-fit multitarget retrieval model for Michelson interferometer for passive atmospheric sounding/environmental satellite observations, APPLIED OPTICS, Vol: 45, Pages: 716-727, ISSN: 1559-128X

Journal article

Magnani L, Fodor W, Machaty Z, Cabot Ret al., 2006, Individual porcine cell lines possess unique expressions pattern of discrete chromatin remodeling factors., 39th Annual Meeting of the Society-for-the-Study-of-Reproduction, Publisher: SOC STUDY REPRODUCTION, Pages: 111-111, ISSN: 0006-3363

Conference paper

Ridolfi M, Magnani L, Carlotti M, Dinelli BMet al., 2004, MIPAS-ENVISAT limb-sounding measurements: trade-off study for improvement of horizontal resolution, APPLIED OPTICS, Vol: 43, Pages: 5814-5824, ISSN: 1559-128X

Journal article

Dinelli BM, Alpaslan D, Carlotti M, Magnani L, Ridolfi Met al., 2004, Multi-target retrieval (MTR): the simultaneous retrieval of pressure, temperature and volume mixing ratio profiles from limb-scanning atmospheric measurements, JOURNAL OF QUANTITATIVE SPECTROSCOPY & RADIATIVE TRANSFER, Vol: 84, Pages: 141-157, ISSN: 0022-4073

Journal article

Piva A, Magnani L, Casadei G, Gatta PP, Selig KM, Patterson JAet al., 2004, Influence of diet on microbial community structure and activity in the intestinal tract of weanling pigs, JOURNAL OF DAIRY SCIENCE, Vol: 87, Pages: 28-28, ISSN: 0022-0302

Journal article

Piva A, Magnani L, Casadei G, Gatta PP, Selig KM, Patterson JAet al., 2004, Influence of diet on microbial community structure and activity in the intestinal tract of weanling pigs, POULTRY SCIENCE, Vol: 83, Pages: 28-28, ISSN: 0032-5791

Journal article

Carli B, Alpaslan D, Carlotti M, Castelli E, Ceccherini S, Dinelli BM, Dudhia A, Flaud JM, Hoepfner M, Jay V, Magnani L, Oelhaf H, Payne V, Piccolo C, Prosperi M, Raspollini P, Remedios J, Ridolfi M, Spang Ret al., 2004, First results of MIPAS/ENVISAT with operational Level 2 code, CLIMATE CHANGE PROCESSES IN THE STRATOSPHERE, EARTH-ATMOSPHERE-OCEAN SYSTEMS, AND OCEANOGRAPHIC PROCESSES FROM SATELLITE DATA, Vol: 33, Pages: 1012-1019, ISSN: 0273-1177

Journal article

Piva A, Magnani L, Casadei G, Gatta PP, Selig KM, Patterson JAet al., 2004, Influence of diet on microbial community structure and activity in the intestinal tract of weanling pigs, JOURNAL OF ANIMAL SCIENCE, Vol: 82, Pages: 28-28, ISSN: 0021-8812

Journal article

Raspollini P, Carli B, Carlotti M, Ceccherini S, Dinelli BM, Dudhia A, Flaud JM, Hopfner M, Jay V, Magnani L, Oelhaf H, Piccolo C, Prosperi M, Remedios J, Ridolfi M, Spang Ret al., 2003, Level 2 near real time analysis of MIPAS measurements on ENVISAT, Conference on Remote Sensing of Clouds and the Atmosphere VII, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, Pages: 324-334, ISSN: 0277-786X

Conference paper

Ridolfi M, Carlotti M, Dinelli BM, Magnani L, Raspollini Pet al., 2002, GEO-FIT approach to the analysis of limb-scanning satellite measurements, REMOTE SENSING OF CLOUDS AND THE ATMOSPHERE VI, Vol: 4539, Pages: 369-380, ISSN: 0277-786X

Journal article

Perone Y, Farrugia AJ, Meira AR, Győrffy B, Ion C, Uggetti A, Patten D, Chronopoulos A, Faronato M, Shousha S, Steel JH, Davies C, Patel N, Rio Hernandez AD, Coombes C, Pruneri G, Lim A, Calvo F, Magnani Let al., SREBP1 drives KRT80-dependent cytoskeletal changes and invasive behavior in endocrine resistant ERα breast cancer

<jats:title>Abstract</jats:title><jats:p>Approximately 30% of women diagnosed with ERα breast cancer relapse with metastatic disease following adjuvant treatment with endocrine therapies<jats:sup>1,2</jats:sup>. The connection between acquisition of drug resistance and invasive potential is poorly understood. In this study, we demonstrate that the type II keratin topological associating domain (TAD)<jats:sup>3</jats:sup> undergoes epigenetic reprogramming in cells that develop resistance to aromatase inhibitors (AI), leading to keratin 80 (KRT80) upregulation. In agreement, an increased number of KRT80-positive cells are observed at relapse <jats:italic>in vivo</jats:italic> while KRT80 expression associates with poor outcome using several clinical endpoints. KRT80 expression is driven by <jats:italic>de novo</jats:italic> enhancer activation by sterol regulatory element-binding protein 1<jats:sup>4</jats:sup> (SREBP1). KRT80 upregulation directly promotes cytoskeletal rearrangements at the leading edge, increased focal adhesion maturation and cellular stiffening, which collectively promote cancer cell invasion. Shear-wave elasticity imaging of prospective patients shows that KRT80 levels correlate with stiffer tumors <jats:italic>in vivo</jats:italic>. Collectively, our data uncover an unpredicted and potentially targetable direct link between epigenetic and cytoskeletal reprogramming promoting cell invasion in response to chronic AI treatment.</jats:p>

Journal article

Tsolaki E, Doran W, Magnani L, Olivo A, Herrmann IK, Bertazzo Set al., Invasive breast tumors are characterized by the presence of crystalline nanoparticles

<jats:p>The presence of calcification in tumours has been known for decades<jats:sup>1</jats:sup>. Indeed, calcified breast tissue is a fundamental criterion for early breast cancer diagnosis, indicative of malignancies<jats:sup>2</jats:sup>, and their appearance is used to distinguish between benign and malignant in breast biopsies<jats:sup>3,4</jats:sup>. However, an in-depth characterization of the nature and origin of tumour tissue calcification remains elusive<jats:sup>5–8</jats:sup>. Here, we report the presence of nano and micron-sized spherical particles made of highly crystalline whitlockite that are exclusively found in the arterial wall of malignant invasive tumours. By applying nanoanalytical methods to healthy, benign and malignant tumour breast tissue biopsies from patients, we show that poorly crystalline apatite can be found in all breast tissue samples, whereas spherical crystalline whitlockite particles are present only in invasive cancers, mainly in areas close to the lumen of the arterial wall. Moreover, we demonstrate that the concentration of these spherical crystalline particles increases with the grade of disease, and that their size can be related to tumour type. Therefore, our results not only provide new insight into calcification of tumour tissue, but also enable a precise, yet simple route of breast cancer diagnosis and staging.</jats:p>

Journal article

Patten DK, Corleone G, Győrffy B, Erdős E, Saiakhova A, Goddard K, Vingiani A, Shousha S, Pongor LS, Hadjiminas DJ, Schiavon G, Barry P, Palmieri C, Coombes RC, Scacheri P, Pruneri G, Magnani Let al., Enhancers mapping uncovers phenotypic heterogeneity and evolution in patients with luminal breast cancer

<jats:title>Abstract</jats:title><jats:p>The degree of intrinsic and interpatient phenotypic heterogeneity and its role in tumour evolution is poorly understood. Phenotypic divergence can be achieved via the inheritance of alternative transcriptional programs<jats:sup>1,2</jats:sup>. Cell-type specific transcription is maintained through the activation of epigenetically-defined regulatory regions including promoters and enhancers<jats:sup>1,3,4</jats:sup>. In this work, we annotated the epigenome of 47 primary and metastatic oestrogen-receptor (ERα)-positive breast cancer specimens from clinical samples, and developed strategies to deduce phenotypic heterogeneity from the regulatory landscape, identifying key regulatory elements commonly shared across patients. Highly shared regions contain a unique set of regulatory information including the motif for the transcription factor YY1. <jats:italic>In vitro</jats:italic> work shows that YY1 is essential for ERα transcriptional activity and defines the critical subset of functional ERα binding sites driving tumor growth in most luminal patients. YY1 also control the expression of genes that mediate resistance to endocrine treatment. Finally, we show that H3K27ac levels at active enhancer elements can be used as a surrogate of intra-tumor phenotypic heterogeneity, and to track expansion and contraction of phenotypic subpopulations throughout breast cancer progression. Tracking YY1 and SLC9A3R1 positive clones in primary and metastatic lesions, we show that endocrine therapies drive the expansion of phenotypic clones originally underrepresented at diagnosis. Collectively, our data show that epigenetic mechanisms significantly contribute to phenotypic heterogeneity and evolution in systemically treated breast cancer patients.</jats:p>

Journal article

Acar A, Nichol D, Fernandez-Mateos J, Cresswell GD, Barozzi I, Hong SP, Spiteri I, Stubbs M, Burke R, Stewart A, Vlachogiannis G, Maley CC, Magnani L, Valeri N, Banerji U, Sottoriva Aet al., Exploiting evolutionary herding to control drug resistance in cancer

<jats:title>Abstract</jats:title><jats:p>Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased growth rate or increased sensitivity to another drug due to evolutionary trade-offs. This weakness can be exploited in the clinic using an approach called ‘evolutionary herding’ that aims at controlling the tumour cell population to delay or prevent resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here we present a novel approach for evolutionary herding based on a combination of single-cell barcoding, very large populations of 10<jats:sup>8</jats:sup>–10<jats:sup>9</jats:sup>cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary herding in non-small cell lung cancer, showing that herding allows shifting the clonal composition of a tumour in our favour, leading to collateral drug sensitivity and proliferative fitness costs. Through genomic analysis and single-cell sequencing, we were also able to determine the mechanisms that drive such evolved sensitivity. Our approach allows modelling evolutionary trade-offs experimentally to test patient-specific evolutionary herding strategies that can potentially be translated into the clinic to control treatment resistance.</jats:p>

Journal article

Hong SP, Chan TE, Lombardo Y, Corleone G, Rotmensz N, Pruneri G, McEwen KR, Coombes RC, Barozzi I, Magnani Let al., Single-cell Transcriptomics reveals multi-step adaptations to endocrine therapy

<jats:title>Abstract</jats:title><jats:p>Resistant tumours are thought to arise from the action of Darwinian selection on genetically heterogenous cancer cell populations. However, simple clonal selection is inadequate to describe the late relapses often characterising luminal breast cancers treated with endocrine therapy (ET), suggesting a more complex interplay between genetic and non-genetic factors. Partially, this is due to our limited understanding on the effect of ET at the single cell level. In the present study, we dissect the contributions of clonal genetic diversity and transcriptional plasticity during the early and late phases of ET at single-cell resolution. Using single-cell RNA-sequencing and imaging we disentangle the transcriptional variability of plastic cells and define a rare sub-population of pre-adapted (PA) cells which undergoes further transcriptomic reprogramming and copy number changes to acquire full resistance. PA cells show reduced oestrogen receptor α activity but increased features of quiescence and migration. We find evidence for sub-clonal expression of this PA signature in primary tumours and for dominant expression in clustered circulating tumour cells. We propose a multi-step model for ET resistance development and advocate the use of stage-specific biomarkers.</jats:p>

Journal article

Borgoni S, Sofyalı E, Soleimani M, Wilhelm H, Müller-Decker K, Will R, Noronha A, Verschure PJ, Yarden Y, Magnani L, van Kampen AHC, Moerland PD, Wiemann Set al., Time-resolved profiling reveals ATF3 as a novel mediator of endocrine resistance in breast cancer

<jats:title>Abstract</jats:title><jats:p>Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α (ERα) account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, 40% of these tumors eventually relapse due to resistance development and further treatment of these patients is highly ineffective. In this study we profiled the early phases of the resistance development process to uncover drivers of this phenomenon. Time-resolved analysis revealed that ATF3, a member of the ATF/CREB family of transcription factors, acts as a novel regulator of the response to therapy via rewiring of central signaling processes towards the adaptation to endocrine treatment. ATF3 was found to be essential in controlling crucial processes such as proliferation, cell cycle and apoptosis during the early response to treatment through the regulation of MAPK/AKT signaling pathways. Its essential role was confirmed <jats:italic>in vivo</jats:italic> in a mouse model and elevated expression of ATF3 was verified in patient datasets, adding clinical relevance to our findings. This study proposes ATF3 as a novel mediator of endocrine resistance development in breast cancer and elucidates its role in the regulation of downstream pathways activities.</jats:p>

Journal article

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