Imperial College London

DrNikolaosTrasanidis

Faculty of MedicineDepartment of Immunology and Inflammation

Honorary Research Fellow
 
 
 
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Contact

 

nikolaos.trasanidis12

 
 
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Location

 

4N5Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

18 results found

Wang L, Trasanidis N, Wu T, Dong G, Hu M, Bauer DEE, Pinello Let al., 2023, Dictys: dynamic gene regulatory network dissects developmental continuum with single-cell multiomics, NATURE METHODS, Vol: 20, Pages: 1368-+, ISSN: 1548-7091

Journal article

Trasanidis N, Katsarou A, Ponnusamy K, Shen Y-A, Kostopoulos I, Bergonia B, Keren K, Reema P, Xiao X, Szydlo RM, Sabbattini PMR, Roberts IAG, Auner HW, Naresh KN, Chaidos A, Wang T-L, Magnani L, Caputo VS, Karadimitris Aet al., 2022, Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma, BLOOD, Vol: 139, Pages: 1939-1953, ISSN: 0006-4971

Journal article

Ponnusamy K, Tzioni MM, Begum M, Robinson ME, Caputo VS, Katsarou A, Trasanidis N, Xiao X, Kostopoulos I, Iskander D, Roberts I, Trivedi P, Auner HW, Naresh K, Chaidos A, Karadimitris Aet al., 2022, The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma, HAEMATOLOGICA, Vol: 107, Pages: 721-732, ISSN: 0390-6078

Journal article

Trasanidis N, Katsarou A, Ponnusamy K, Shen Y-A, Kostopoulos IV, Bergonia B, Keren K, Reema P, Xiao X, Szydlo RM, Sabbattini PMR, Roberts IAG, Auner HW, Naresh KN, Chaidos A, Wang T-L, Magnani L, Caputo VS, Karadimitris Aet al., 2021, Systems medicine dissection of chromosome 1q amplification reveals oncogenic regulatory circuits and informs targeted therapy in cancer

<jats:title>Abstract</jats:title><jats:p>Understanding the biological and clinical impact of copy number aberrations (CNA) in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring adverse prognosis in several cancers, including the blood cancer, multiple myeloma (MM). Although several chr1q genes portend high-risk MM disease, the underpinning molecular aetiology remains elusive. Here we integrate patient multi-omics datasets with genetic variables to identify 103 adverse prognosis genes in chr1q-amp MM. Amongst these, the transcription factor PBX1 is ectopically expressed by genetic amplification and epigenetic activation of its own preserved 3D regulatory domain. By binding to reprogrammed super-enhancers, PBX1 directly regulates critical oncogenic pathways, whilst in co-operation with FOXM1, activates a proliferative gene signature which predicts adverse prognosis across multiple cancers. Notably, pharmacological disruption of the PBX1-FOXM1 axis, including with a novel PBX1 inhibitor is selectively toxic against chr1q-amp cancer cells. Overall, our systems medicine approach successfully identifies CNA-driven oncogenic circuitries, links them to clinical phenotypes and proposes novel CNA-targeted therapy strategies in cancer.</jats:p><jats:sec><jats:title>Significance</jats:title><jats:p>We provide a comprehensive systems medicine strategy to unveil oncogenic circuitries and inform novel precision therapy decisions against CNA in cancer. This first clinical multi-omic analysis of chr1q-amp in MM identifies a central PBX1-FOXM1 regulatory axis driving high-risk prognosis, as a novel therapeutic target against chr1q-amp in cancer.</jats:p></jats:sec>

Journal article

Karadimitris A, 2021, Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma, Nature Communications, Vol: 12, Pages: 1-16, ISSN: 2041-1723

Multiple myeloma is a genetically heterogeneous cancer of the bone marrow plasma cells (PC). Distinct myeloma transcriptome profiles are primarily driven by myelomainitiating events (MIE) and converge into a mutually exclusive overexpression of the CCND1 and CCND2 oncogenes. Here, with reference to their normal counterparts, we find that myeloma PC enhanced chromatin accessibility combined with paired transcriptome profiling can classify MIE-defined genetic subgroups. Across and within different MM genetic subgroups, we ascribe regulation of genes and pathways critical for myeloma biology to unique or shared, developmentally activated or de novo formed candidate enhancers. Such enhancers co-opt recruitment of existing transcription factors, which although not transcriptionally deregulated per se, organise aberrant gene regulatory networks that help identify myeloma cell dependencies with prognostic impact. Finally, we identify and validate the critical super-enhancer that regulates ectopic expression of CCND2 in a subset of patients with MM and in chronic lymphocytic leukemia.

Journal article

Iskander D, Wang G, Heuston EF, Christodoulidou C, Psaila B, Ponnusamy K, Ren H, Mokhtari Z, Robinson M, Chaidos A, Trivedi P, Trasanidis N, Katsarou A, Szydlo R, Palii CG, Zaidi MH, Al-Oqaily Q, Caputo VS, Roy A, Harrington Y, Karnik L, Naresh K, Mead AJ, Thongjuea S, Brand M, de la Fuente J, Bodine DM, Roberts I, Karadimitris Aet al., 2021, Single-cell profiling of human bone marrow progenitors reveals mechanisms of failing erythropoiesis in Diamond-Blackfan anemia, SCIENCE TRANSLATIONAL MEDICINE, Vol: 13, ISSN: 1946-6234

Journal article

Wang L, Zhang Q, Qin Q, Trasanidis N, Vinyard M, Chen H, Pinello Let al., 2021, Current progress and potential opportunities to infer single-cell developmental trajectory and cell fate, CURRENT OPINION IN SYSTEMS BIOLOGY, Vol: 26, Pages: 1-11, ISSN: 2452-3100

Journal article

Ferdous Z, Fuchs S, Behrends V, Trasanidis N, Vlachou D, Christophides GKet al., 2021, Anopheles coluzziistearoyl-CoA desaturase is essential for adult female survival and reproduction upon blood feeding, PLoS Pathogens, Vol: 17, ISSN: 1553-7366

Vitellogenesis and oocyte maturation require anautogenous female Anopheles mosquitoes to obtain a bloodmeal from a vertebrate host. The bloodmeal is rich in proteins that are readily broken down into amino acids in the midgut lumen and absorbed by the midgut epithelial cells where they are converted into lipids and then transported to other tissues including ovaries. The stearoyl-CoA desaturase (SCD) plays a pivotal role in this process by converting saturated (SFAs) to unsaturated (UFAs) fatty acids; the latter being essential for maintaining cell membrane fluidity amongst other housekeeping functions. Here, we report the functional and phenotypic characterization of SCD1 in the malaria vector mosquito Anopheles coluzzii. We show that RNA interference (RNAi) silencing of SCD1 and administration of sterculic acid (SA), a small molecule inhibitor of SCD1, significantly impact on the survival and reproduction of female mosquitoes following blood feeding. Microscopic observations reveal that the mosquito thorax is quickly filled with blood, a phenomenon likely caused by the collapse of midgut epithelial cell membranes, and that epithelial cells are depleted of lipid droplets and oocytes fail to mature. Transcriptional profiling shows that genes involved in protein, lipid and carbohydrate metabolism and immunity-related genes are the most affected by SCD1 knock down (KD) in blood-fed mosquitoes. Metabolic profiling reveals that these mosquitoes exhibit increased amounts of saturated fatty acids and TCA cycle intermediates, highlighting the biochemical framework by which the SCD1 KD phenotype manifests as a result of a detrimental metabolic syndrome. Accumulation of SFAs is also the likely cause of the potent immune response observed in the absence of infection, which resembles an auto-inflammatory condition. These data provide insights into mosquito bloodmeal metabolism and lipid homeostasis and could inform efforts to develop novel interventions against mosquito-borne

Journal article

Caputo VS, Trasanidis N, Xiao X, Robinson ME, Katsarou A, Ponnusamy K, Prinjha RK, Smithers N, Chaidos A, Auner HW, Karadimitris Aet al., 2021, Brd2/4 and Myc regulate alternative cell lineage programmes during early osteoclast differentiation in vitro, iScience, Vol: 24, Pages: 1-31, ISSN: 2589-0042

Osteoclast development in response to RANKL is critical for bone homeostasis in health and in disease. The early and direct chromatin regulatory changes imparted by the BET chromatin readers Brd2-4 and osteoclast-affiliated transcription factors (TF) during osteoclastogenesis are not known. Here, we demonstrate that in response to RANKL, early osteoclast development entails regulation of two alternative cell fate transcriptional programmes, osteoclast vs macrophage, with repression of the latter following activation of the former. Both programmes are regulated in a non-redundant manner by increased chromatin binding of Brd2 at promoters and of Brd4 at enhancers/super-enhancers. Myc, the top RANKL-induced TF, regulates osteoclast development in co-operation with Brd2/4 and Max and by establishing negative and positive regulatory loops with other lineage-affiliated TF. These insights into the transcriptional regulation of osteoclastogenesis suggest the clinical potential of selective targeting of Brd2/4 to abrogate pathological OC activation.

Journal article

Iskander D, Wang G, Heuston EF, Christodoulidou C, Psaila B, Robinson ME, Chaidos A, Trivedi P, Trasanidis N, Katsarou A, Szydlo R, Al-Oqaily Q, Caputo VS, Ponnusamy K, Roy A, Karnik L, Naresh K, Mead AJ, Thongjuea S, Brand M, De la Fuente J, Bodine DM, Roberts Iet al., 2020, Single-Cell Transcriptional Landscapes of Human Bone Marrow Reveal Distinct Erythroid Phenotypes Underpinned By Genotype in Diamond-Blackfan Anemia, 62nd Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971

Conference paper

Ponnusamy K, Tzioni MM, Begum M, Robinson ME, Caputo VS, Katsarou A, Trasanidis N, Xiao X, Kostopoulos IV, Iskander D, Roberts I, Trivedi P, Auner HW, Naresh K, Chaidos A, Karadimitris Aet al., 2020, The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma

<jats:title>Abstract</jats:title><jats:p>ZBP1 is an inducible, non-constitutively expressed cellular nucleic acid sensor that triggers type I interferon (IFN) responses via phosphorylation and activation of the transcription factor (TF) IRF3 by TBK1. However, the role of the ZBP1-IRF3 axis in cancer is not known. Here we show that ZBP1 is selectively and constitutively expressed in late B cell development and it is required for optimal T cell-dependent humoral immune responses. In the plasma cell (PC) cancer multiple myeloma, interaction of constitutively expressed ZBP1 with TBK1 and IRF3 results in IRF3 phosphorylation. Notably, rather than IFN type I response genes, IRF3 directly activates, in part through co-operation with the PC lineage-defining TF IRF4, cell cycle genes thus promoting myeloma cell proliferation. This generates a novel, potentially therapeutically targetable and relatively selective myeloma cell addiction to the ZBP1-IRF3 axis. These data expand our knowledge of the role of cellular immune sensors in cancer biology.</jats:p>

Journal article

Ferdous Z, Fuchs S, Behrends V, Trasanidis N, Vlachou D, Christophides Get al., 2020, <i>Anopheles coluzzii</i>stearoyl-CoA desaturase is essential for adult female survival and reproduction upon blood feeding

Vitellogenesis and oocyte maturation require anautogenous female Anopheles mosquitoes to obtain a bloodmeal from a vertebrate host. The bloodmeal is rich in proteins that are readily broken down into amino acids in the midgut lumen and absorbed by the midgut epithelial cells where they are converted into lipids and then transported to other tissues including ovaries. The stearoyl-CoA desaturase (SCD) plays a pivotal role in this process by converting saturated (SFAs) to unsaturated (UFAs) fatty acids; the latter being essential for maintaining cell membrane fluidity amongst other housekeeping functions. Here, we report the functional and phenotypic characterization of SCD1 in the malaria vector mosquito Anopheles coluzzii . We show that RNA interference (RNAi) silencing of SCD1 and administration of sterculic acid (SA), a small molecule inhibitor of SCD1, significantly impact on the survival and reproduction of female mosquitoes following blood feeding. Microscopic observations reveal that the mosquito thorax is quickly filled with blood, a phenomenon likely caused by the collapse of midgut epithelial cell membranes, and that epithelial cells are depleted of lipid droplets and oocytes fail to mature. Transcriptional profiling shows that genes involved in protein, lipid and carbohydrate metabolism and immunity-related genes are the most affected by SCD1 knock down (KD) in blood-fed mosquitoes. Metabolic profiling reveals that these mosquitoes exhibit increased amounts of saturated fatty acids and TCA cycle intermediates, highlighting the biochemical framework by which the SCD1 KD phenotype manifests as a result of a detrimental metabolic syndrome. Accumulation of SFAs is also the likely cause of the potent immune response observed in the absence of infection, which resembles an auto-inflammatory condition. These data provide insights into mosquito bloodmeal metabolism and lipid homeostasis and could inform efforts to develop novel interventions against mosquito-borne

Journal article

Ponnusamy K, Tzioni M-M, Begum M, Robinson ME, Caputo VS, Katsarou A, Trasanidis N, Xiao X, Kostopoulos IV, Iskander D, Roberts I, Trivedi P, Auner HW, Naresh K, Chaidos A, Karadimitris Aet al., 2019, Novel ZBP1-IRF3 Dependency in Multiple Myeloma Mediated By IRF3-Driven Regulation of Cell Cycle Genes, BLOOD, Vol: 134, ISSN: 0006-4971

Journal article

Trasanidis N, Alvarez-Benayas J, Katsarou A, Chaidos A, May PC, Ponnusamy K, Xiao X, Bua M, Atta M, Roberts I, Auner HW, Hatjiharissi E, Papaioannou M, Caputo VS, Sudbery I, Karadimitris Aet al., 2019, Distinct Chromatin Accessibility Changes, Aberrant Transcription Factor Networks Combined with Novel Oncogenic Enhancers Characterise Myeloma-Initiating Genetic Events, 61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971

Conference paper

Katsarou A, Trasanidis N, Alvarez-Benayas J, Papaleonidopoulou F, Keren K, Kostopoulos IV, Ponnusamy K, Xiao X, Feldhahn N, Roberts I, Hatjiharissi E, Papaioannou M, Sudbery I, Chaidos A, Caputo VS, Karadimitris Aet al., 2019, Oncogenic MAF in Co-Operation with IRF4 Confers Extensive Chromatin Re-Arrangement in Plasma Cells and Generates 'Neo-Enhancers' That Regulate Genes Critical for Myeloma Biology, 61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971

Conference paper

Caputo VS, Trasanidis N, Xiao X, Robinson ME, Katsarou A, Ponnusamy K, Chaidos A, Auner HW, Roberts I, Karadimitris Aet al., 2019, Myc and Bet Proteins Orchestrate the Early Regulatory Genome Changes Required for Osteoclast Lineage Commitment, 61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971

Conference paper

Trasanidis N, Katsarou A, Bergonia B, Keren K, Kostopoulos IV, Ponnusamy K, Paudel R, Xiao X, Auner HW, Roberts I, Naresh K, Chaidos A, Magnani L, Caputo VS, Karadimitris Aet al., 2019, PBX1 Co-Operates with FOXM1 to Regulate Myeloma Cell Proliferation and to Define an Ultra High-Risk chr1q Gain Myeloma Patient Subgroup, BLOOD, Vol: 134, ISSN: 0006-4971

Journal article

Caputo V, Goudevenou K, Trasanidis N, Petevi K, Xiao X, Ponnusamy K, Iskander D, Pitcher D, Rotolo A, Auner HW, Chaidos A, Karadimitris Aet al., 2017, Myeloma Cell Addiction to the Transcription Factor TCF11, 59th Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971

Conference paper

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