Imperial College London

Professor Irene Roberts

Faculty of MedicineDepartment of Immunology and Inflammation

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3313 2163irene.roberts

 
 
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Assistant

 

Miss Karen Linfield +44 (0)20 3313 3238

 
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Location

 

4S10BHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

183 results found

O'Byrne S, Elliott N, Rice S, Buck G, Fordham N, Garnett C, Godfrey L, Crump NT, Wright G, Inglott S, Hua P, Psaila B, Povinelli B, Knapp DJHF, Agraz-Doblas A, Bueno C, Varela I, Bennett P, Koohy H, Watt SM, Karadimitris A, Mead AJ, Ancliff P, Vyas P, Menendez P, Milne TA, Roberts I, Roy Aet al., 2019, Discovery of a CD10 negative B-progenitor in human fetal life identifies unique ontogeny-related developmental programs, Blood, Vol: 134, Pages: 1059-1071, ISSN: 0006-4971

Human lymphopoiesis is a dynamic life-long process that starts in utero 6 weeks post-conception. Fetal B-lymphopoiesis remains poorly defined and yet is key to understanding leukemia initiation in early life. Here, we provide a comprehensive analysis of the human fetal B-cell developmental hierarchy. We report the presence in fetal tissues of two distinct CD19+ B-progenitors, an adult-type CD10+ve ProB-progenitor and a new CD10-ve PreProB-progenitor, and describe their molecular and functional characteristics. PreProB- and ProB-progenitors appear early in the first trimester in embryonic liver, followed by a sustained second wave of B-progenitor development in fetal BM, where together they form >40% of the total HSC/progenitor pool. Almost one-third of fetal B-progenitors are CD10-ve PreProB-progenitors while, by contrast, PreProB-progenitors are almost undetectable (0.53{plus minus}0.24%) in adult BM. Single-cell transcriptomics and functional assays place fetal PreProB- upstream of ProB-progenitors, identifying them as the first B-lymphoid restricted progenitor in human fetal life. Fetal BM PreProB- and ProB-progenitors both give rise solely to B-lineage cells yet they are transcriptionally distinct. Like their fetal counterparts, adult BM PreProB-progenitors give rise only to B-lineage cells in vitro and express the expected B-lineage gene expression program. However, fetal PreProB-progenitors, display a distinct, ontogeny-related gene expression pattern which is not seen in adult PreProB-progenitors; and share transcriptomic signatures with CD10-ve B-progenitor infant acute lymphoblastic leukemia blast cells. These data identify PreProB-progenitors as the earliest B-lymphoid-restricted progenitor in human fetal life, and suggest that this fetal-restricted committed B-progenitor might provide a permissive cellular context for prenatal B-progenitor leukemia initiation.

Journal article

Iskander D, Roberts I, Rees C, Szydlo R, Alikian M, Neale M, Harrington Y, Kelleher P, Karadimitris A, de la Fuente Jet al., 2019, Impaired cellular and humoral immunity is a feature of Diamond-Blackfan anaemia; experience of 107 unselected cases in the United Kingdom., British Journal of Haematology, Vol: 186, Pages: 321-326, ISSN: 1365-2141

Diamond-Blackfan anaemia (DBA) is a rare bone marrow failure syndrome characterised by anaemia, congenital anomalies and cancer predisposition. Although infections are the second leading cause of mortality in non-transplanted patients, immune function is largely unexplored. We identified quantitative deficits in serum immunoglobulins and/or circulating T, natural killer and B lymphocytes in 59 of 107 unselected patients (55·1%) attending our centre over a 7-year period. Immune abnormalities were independent of ribosomal protein genotype and arose in both steroid-treated and steroid-untreated patients. In summary, these data highlight the high prevalence and spectrum of infections and immune defects in DBA.

Journal article

Roberts I, Fordham NJ, Rao A, Bain BJet al., 2018, Neonatal leukaemia, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 182, Pages: 170-184, ISSN: 0007-1048

Journal article

Bain BJ, Roberts I, Fordham N, Rao Aet al., 2018, Neonatal leukaemia, British Journal of haematology, ISSN: 0007-1048

Journal article

O'Byrne S, Elliott N, Buck G, Liu B, Povinelli B, Fordham N, Louka E, Bartolovic K, Karadimitris A, Mead A, Roberts I, Roy Aet al., 2017, RE-ORDERING THE B CELL DEVELOPMENT HIERARCHY IN HUMAN FETAL BONE MARROW: CHARACTERISATION OF A NOVEL HUMAN FETAL B PROGENITOR, 22nd Congress of the European-Hematology-Association, Publisher: FERRATA STORTI FOUNDATION, Pages: 80-80, ISSN: 0390-6078

Conference paper

Roy A, Bystry V, Bohn G, Goudevenou K, Reigl T, Papaioannou M, Krejci A, O'Byrne S, Chaidos A, Grioni A, Darzentas N, Roberts IAG, Karadimitris Aet al., 2017, High resolution IgH repertoire analysis reveals fetal liver as the likely origin of life-long, innate B lymphopoiesis in humans, Clinical Immunology, Vol: 183, Pages: 8-16, ISSN: 1521-6616

The ontogeny of the natural, public IgM repertoire remains incompletely explored. Here, high-resolution immunogenetic analysis of B cells from (unrelated) fetal, child, and adult samples, shows that although fetal liver (FL) and bone marrow (FBM) IgM repertoires are equally diversified, FL is the main source of IgM natural immunity during the 2nd trimester. Strikingly, 0.25% of all prenatal clonotypes, comprising 18.7% of the expressed repertoire, are shared with the postnatal samples, consistent with persisting fetal IgM+ B cells being a source of natural IgM repertoire in adult life. Further, the origins of specific stereotypic IgM+ B cell receptors associated with chronic lymphocytic leukemia, can be traced back to fetal B cell lymphopoiesis, suggesting that persisting fetal B cells can be subject to malignant transformation late in life. Overall, these novel data provide unique insights into the ontogeny of physiological and malignant B lymphopoiesis that spans the human lifetime.

Journal article

Roy A, Bystry V, Bohn G, Goudevenou K, Reigl T, Papaioannou M, Krejci A, O'Byrne S, Chaidos A, Grioni A, Darzentas N, Roberts I, Karadimitris Aet al., 2016, High Resolution Igh Repertoire Analysis Reveals the Human Fetal Liver As the Origin of Life-Long, Innate B Lymphopoiesis, 58th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971

Conference paper

Roberts I, de la Fuente J, 2016, Sickle cell disease: the price of cure, BLOOD, Vol: 128, Pages: 2486-+, ISSN: 0006-4971

Journal article

Roy A, Liu B, Goudevenou K, Bohn G, Filippi S, Elliott N, Cowan G, O'Connor D, Bhatnagar N, Chou S, Weiss M, Vyas P, Karadimitris A, Roberts Iet al., 2016, GENOME WIDE DYSREGULATION OF GENE EXPRESSION BY TRISOMY 21 IN FETAL LIVER HAEMATOPOIETIC STEM AND PROGENITOR CELLS, 21st Congress of the European-Hematology-Association, Publisher: FERRATA STORTI FOUNDATION, Pages: 120-120, ISSN: 0390-6078

Conference paper

Psaila B, Barkas N, Iskander D, Roy A, Anderson S, Ashley N, Caputo VS, Lichtenberg J, Loaiza S, Bodine DM, Karadimitris A, Mead AJ, Roberts Iet al., 2016, Single-cell profiling of human megakaryocyte-erythroid progenitors identifies distinct megakaryocyte and erythroid differentiation pathways, Genome Biology, Vol: 17, Pages: 1-19, ISSN: 1474-760X

BACKGROUND: Recent advances in single-cell techniques have provided the opportunity to finely dissect cellular heterogeneity within populations previously defined by "bulk" assays and to uncover rare cell types. In human hematopoiesis, megakaryocytes and erythroid cells differentiate from a shared precursor, the megakaryocyte-erythroid progenitor (MEP), which remains poorly defined. RESULTS: To clarify the cellular pathway in erythro-megakaryocyte differentiation, we correlate the surface immunophenotype, transcriptional profile, and differentiation potential of individual MEP cells. Highly purified, single MEP cells were analyzed using index fluorescence-activated cell sorting and parallel targeted transcriptional profiling of the same cells was performed using a specifically designed panel of genes. Differentiation potential was tested in novel, single-cell differentiation assays. Our results demonstrate that immunophenotypic MEP comprise three distinct subpopulations: "Pre-MEP," enriched for erythroid/megakaryocyte progenitors but with residual myeloid differentiation capacity; "E-MEP," strongly biased towards erythroid differentiation; and "MK-MEP," a previously undescribed, rare population of cells that are bipotent but primarily generate megakaryocytic progeny. Therefore, conventionally defined MEP are a mixed population, as a minority give rise to mixed-lineage colonies while the majority of cells are transcriptionally primed to generate exclusively single-lineage output. CONCLUSIONS: Our study clarifies the cellular hierarchy in human megakaryocyte/erythroid lineage commitment and highlights the importance of using a combination of single-cell approaches to dissect cellular heterogeneity and identify rare cell types within a population. We present a novel immunophenotyping strategy that enables the prospective identification of specific intermediate progenitor populations in erythro-megakaryopoiesis, allowing for in-de

Journal article

Engert A, Balduini C, Brand A, Coiffier B, Cordonnier C, Döhner H, de Wit TD, Eichinger S, Fibbe W, Green T, de Haas F, Iolascon A, Jaffredo T, Rodeghiero F, Salles G, Schuringa JJ, EHA Roadmap for European Hematology Researchet al., 2016, The European Hematology Association Roadmap for European Hematology Research: a consensus document., Haematologica, Vol: 101, Pages: 115-208, ISSN: 0390-6078

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap.The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders.The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.

Journal article

Ersek A, Xu K, Antonopoulos A, Butters TD, Santo AE, Vattakuzhi Y, Williams LM, Goudevenou K, Danks L, Freidin A, Spanoudakis E, Parry S, Papaioannou M, Hatjiharissi E, Chaidos A, Alonzi DS, Twigg G, Hu M, Dwek RA, Haslam SM, Roberts I, Dell A, Rahemtulla A, Horwood NJ, Karadimitris Aet al., 2015, Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease, Journal of Clinical Investigation, Vol: 125, Pages: 2279-2292, ISSN: 1558-8238

Glycosphingolipids (GSLs) are essential constituents of cell membranes and lipid rafts and can modulate signal transduction events. The contribution of GSLs in osteoclast (OC) activation and osteolytic bone diseases in malignancies such as the plasma cell dyscrasia multiple myeloma (MM) is not known. Here, we tested the hypothesis that pathological activation of OCs in MM requires de novo GSL synthesis and is further enhanced by myeloma cell–derived GSLs. Glucosylceramide synthase (GCS) inhibitors, including the clinically approved agent N-butyl-deoxynojirimycin (NB-DNJ), prevented OC development and activation by disrupting RANKL-induced localization of TRAF6 and c-SRC into lipid rafts and preventing nuclear accumulation of transcriptional activator NFATc1. GM3 was the prevailing GSL produced by patient-derived myeloma cells and MM cell lines, and exogenous addition of GM3 synergistically enhanced the ability of the pro-osteoclastogenic factors RANKL and insulin-like growth factor 1 (IGF-1) to induce osteoclastogenesis in precursors. In WT mice, administration of GM3 increased OC numbers and activity, an effect that was reversed by treatment with NB-DNJ. In a murine MM model, treatment with NB-DNJ markedly improved osteolytic bone disease symptoms. Together, these data demonstrate that both tumor-derived and de novo synthesized GSLs influence osteoclastogenesis and suggest that NB-DNJ may reduce pathological OC activation and bone destruction associated with MM.

Journal article

Iskander D, Psaila B, Gerrard G, Chaidos A, Foong HE, Harrington Y, Karnik LC, Roberts I, de la Fuente J, Karadimitris Aet al., 2015, Elucidation of the EP defect in Diamond-Blackfan anemia by characterization and prospective isolation of human EPs, BLOOD, Vol: 125, Pages: 2553-2557, ISSN: 0006-4971

Journal article

Liu B, Filippi S, Roy A, Roberts Iet al., 2015, Stem and progenitor cell dysfunction in human trisomies, EMBO REPORTS, Vol: 16, Pages: 44-62, ISSN: 1469-221X

Journal article

O'Connor D, Liu B, Cowan G, Roy A, Goudevenou K, Bhatnagar N, Tunstall O, de la Fuente J, Karadimitris A, Roberts Iet al., 2014, Trisomy 21-Associated Abnormalities in IGF Signalling and the Fetal Microenvironment Both Contribute to Disruption of Fetal Hematopoiesis in Down Syndrome, 56th Annual Meeting of the American-Society-of-Hematology, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971

Conference paper

Bhatnagar N, Perkins K, Filippi S, Richmond H, Bonnici J, Alford K, Hall G, Juban G, McGowan S, Roy A, Elliott N, Stumpf M, Norton A, Vyas P, Roberts Iet al., 2014, Clinical and Hematologic Impact of Fetal and Perinatal Variables on Mutant GATA1 Clone Size in Neonates with Down Syndrome, BLOOD, Vol: 124, ISSN: 0006-4971

Journal article

Roy A, Bohn G, Goudevenou K, Cowan G, Bhatnagar N, O'Connor D, Tunstall O, Chan J, Bennett P, Kumar S, Iskander D, Inglott S, Liu B, Ancliff P, Karadimitris A, Roberts Iet al., 2014, Developmental Stage Specific B-Progenitor Expansion in Normal Fetal Bone Marrow Is Absent in Down Syndrome: Implications for Infant ALL, 56th Annual Meeting of the American-Society-of-Hematology, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971

Conference paper

Costa JR, Caputo VS, Makarona K, Layton DM, Roberts IAG, Almeida AM, Karadimitris Aet al., 2014, Cell-type-specific transcriptional regulation of PIGM underpins the divergent hematologic phenotype in inherited GPl deficiency, BLOOD, Vol: 124, Pages: 3151-3154, ISSN: 0006-4971

Journal article

DeBaun MR, Rodeghier M, Cohen R, Kirkham FJ, Rosen CL, Roberts I, Cooper B, Stocks J, Wilkey O, Inusa B, Warner JO, Strunk RCet al., 2014, Factors predicting future ACS episodes in children with sickle cell anemia, AMERICAN JOURNAL OF HEMATOLOGY, Vol: 89, Pages: E212-E217, ISSN: 0361-8609

Journal article

Rosen CL, Debaun MR, Strunk RC, Redline S, Seicean S, Craven DI, Gavlak JCD, Wilkey O, Inusa B, Roberts I, Goodpaster RL, Malow B, Rodeghier M, Kirkham FJet al., 2014, Obstructive Sleep Apnea and Sickle Cell Anemia, PEDIATRICS, Vol: 134, Pages: 273-281, ISSN: 0031-4005

Journal article

Makarona K, Caputo VS, Costa JR, Liu B, O'Connor D, Iskander D, Roper D, Robertson L, Bhatnagar N, Terpos E, Georgiou E, Papaioannou M, Layton DM, Luzzatto L, Roberts I, Karadimitris Aet al., 2014, Transcriptional and epigenetic basis for restoration of G6PD enzymatic activity in human G6PD-deficient cells, BLOOD, Vol: 124, Pages: 134-141, ISSN: 0006-4971

Journal article

Strunk RC, Cohen RT, Cooper BP, Rodeghier M, Kirkham FJ, Warner JO, Stocks J, Kirkby J, Roberts I, Rosen CL, Craven DI, DeBaun MRet al., 2014, Wheezing Symptoms and Parental Asthma Are Associated with a Physician Diagnosis of Asthma in Children with Sickle Cell Anemia, JOURNAL OF PEDIATRICS, Vol: 164, Pages: 821-U201, ISSN: 0022-3476

Journal article

Gluckman E, Ruggeri A, Labopin M, Volt F, Devergie A, Cavazzana M, Cappelli B, Eapen M, Simoes B, Matthes S, Ramanan V, Dalle JH, Roberts I, de la Fuente J, Rocha V, Locatelli F, Peters C, Bernaudin Fet al., 2014, HAEMATOPOIETIC STEM CELL TRANSPLANTATION FOR SICKLE CELL DISEASE: AN INTERNATIONAL SURVEY ON BEHALF OF EUROCORD-MONACORD, EBMT PAEDIATRIC DISEASE WORKING PARTY AND CIBMTR, 40th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation, Publisher: NATURE PUBLISHING GROUP, Pages: S37-S37, ISSN: 0268-3369

Conference paper

Chaidos A, Caputo V, Gouvedenou K, Liu B, Marigo I, Chaudhry MS, Rotolo A, Tough DF, Smithers NN, Bassil AK, Chapman TD, Harker NR, Barbash O, Tummino P, Al-Mahdi N, Haynes AC, Cutler L, Le B, Rahemtulla A, Roberts I, Kleijnen M, Witherington JJ, Parr NJ, Prinjha RK, Karadimitris Aet al., 2014, Potent antimyeloma activity of the novel bromodomain inhibitors I-BET151 and I-BET762, BLOOD, Vol: 123, Pages: 697-705, ISSN: 0006-4971

Journal article

Vannocci T, Kurata H, de la Fuente J, Roberts IA, Porter ACGet al., 2014, Nuclease-stimulated homologous recombination at the human beta-globin gene, JOURNAL OF GENE MEDICINE, Vol: 16, Pages: 1-10, ISSN: 1099-498X

Journal article

Pitcher DS, De Mattos-Shipley K, Wang Z, Tzortzis K, Goudevenou K, Flynn H, Bohn G, Rahemtulla A, Roberts I, Snijders AP, Karadimitris A, Kleijnen MFet al., 2014, Nuclear proteasomes carry a constitutive posttranslational modification which derails SDS-PAGE (but not CTAB-PAGE), Biochimica et Biophysica Acta - Proteins and Proteomics, Vol: 1844, Pages: 2222-2228

We report that subunits of human nuclear proteasomes carry a previously unrecognised, constitutive posttranslational modification. Subunits with this modification are not visualised by SDS-PAGE, which is used in almost all denaturing protein gel electrophoresis. In contrast, CTAB-PAGE readily visualises such modified subunits. Thus, under most experimental conditions, with identical samples, SDS-PAGE yielded gel electrophoresis patterns for subunits of nuclear proteasomes which were misleading and strikingly different from those obtained with CTAB-PAGE. Initial analysis indicates a novel modification of a high negative charge with some similarity to polyADP-ribose, possibly explaining compatibility with (positively-charged) CTAB-PAGE but not (negatively-charged) SDS-PAGE and providing a mechanism for how nuclear proteasomes may interact with chromatin, DNA and other nuclear components.

Journal article

Roberts I, Alford K, Hall G, Juban G, Richmond H, Norton A, Vallance G, Perkins K, Marchi E, McGowan S, Roy A, Cowan G, Anthony M, Gupta A, Ho J, Uthaya S, Curley A, Rasiah SV, Watts T, Nicholl R, Bedford-Russell A, Blumberg R, Thomas A, Gibson B, Halsey C, Lee P-W, Godambe S, Sweeney C, Bhatnagar N, Goriely A, Campbell P, Vyas Pet al., 2013, GATA1-mutant clones are frequent and often unsuspected in babies with Down syndrome: identification of a population at risk of leukemia, BLOOD, Vol: 122, Pages: 3908-3917, ISSN: 0006-4971

Journal article

Roberts I, O'Connor D, Roy A, Cowan G, Vyas Pet al., 2013, The impact of trisomy 21 on foetal haematopoiesis, BLOOD CELLS MOLECULES AND DISEASES, Vol: 51, Pages: 277-281, ISSN: 1079-9796

Journal article

Innes AJ, Beattie R, Sergeant R, Damaj G, Foroni L, Marin D, Kanfer E, Mielke S, Milojkovic D, MacDonald D, Pavlu J, Rahemtulla A, Roberts I, Slade D, Bray E, Goldman J, Apperley J, Szydlo R, Dazzi F, Rezvani Ket al., 2013, Escalating-dose HLA-mismatched DLI is safe for the treatment of leukaemia relapse following alemtuzumab-based myeloablative allo-SCT, BONE MARROW TRANSPLANTATION, Vol: 48, Pages: 1324-1328, ISSN: 0268-3369

Journal article

Maroz A, Reinhardt K, Emmrich S, Dertmann T, Hitzler J, Roberts I, Hennig C, Hansen G, Reinhardt D, Klusmann Jet al., 2013, GATA1S MEDIATES CLONAL EOSINOPHILIA IN PATIENTS WITH DOWN SYNDROME TRANSIENT LEUKEMIA, PEDIATRIC BLOOD & CANCER, Vol: 60, Pages: 6-6, ISSN: 1545-5009

Journal article

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