Imperial College London

DrKikkeriNaresh

Faculty of MedicineDepartment of Immunology and Inflammation

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3313 3969k.naresh

 
 
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Location

 

Office 6, Building 541, G-BlockHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

381 results found

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

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., 2021, The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma., Haematologica

Multiple myeloma is a malignancy of plasma cells (PC) initiated and driven by primary and secondary genetic events. Nevertheless, myeloma PC survival and proliferation might be sustained by non-genetic drivers. Z-DNA-binding protein 1 (ZBP1; also known as DAI) is an interferon-inducible, Z-nucleic acid sensor that triggers RIPK3-MLKL-mediated necroptosis in mice. ZBP1 also interacts with TBK1 and the transcription factor IRF3 but the function of this interaction is unclear, and the role of ZBP1-IRF3 axis in cancer is not known. Here we show that ZBP1 is selectively expressed in late B cell development in both human and mouse cells and it is required for optimal T-cell-dependent humoral immune responses. In myeloma PC, interaction of constitutively expressed ZBP1 with TBK1 and IRF3 results in IRF3 phosphorylation. IRF3 directly binds and activates cell cycle genes, in part through co-operation with the PC lineage-defining transcription factor IRF4, and thereby promoting myeloma cell proliferation. This generates a novel, potentially therapeutically targetable and relatively selective myeloma cell addiction to the ZBP1-IRF3 axis. Our data also show a non-canonical function of constitutive ZBP1 in human cells and expand our knowledge of the role of cellular immune sensors in cancer biology.

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, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971

Conference paper

Ziepert M, Lazzi S, Santi R, Vergoni F, Granai M, Mancini V, Staiger AM, Horn H, Loffler M, Poschel V, Held G, Wulf G, Trumper LH, Schmitz N, Rosenwald A, Sabattini E, Naresh KN, Stein H, Ott G, Leoncini Let al., 2020, A 70% cut-off for MYC protein expression in diffuse large B-cell lymphoma identifies a high-risk group of patients, HAEMATOLOGICA, Vol: 105, Pages: 2667-2670, ISSN: 0390-6078

Journal article

Ziepert M, Lazzi S, Santi R, Vergoni F, Granai M, Mancini V, Staiger A, Horn H, Löffler M, Pöschel V, Held G, Wulf G, Trümper LH, Schmitz N, Rosenwald A, Sabattini E, Naresh KN, Stein H, Ott G, Leoncini Let al., 2020, A 70% cut-off for MYC protein expression in diffuse large B cell lymphoma identifies a high-risk group of patients., Haematologica, Vol: 105, Pages: 2667-2670

Journal article

Hanley B, Naresh KN, Roufosse C, Nicholson AG, Weir J, Cooke GS, Thursz M, Manousou P, Corbett R, Goldin R, Al-Sarraj S, Abdolrasouli A, Swann OC, Baillon L, Penn R, Barclay WS, Viola P, Osborn Met al., 2020, Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study, The Lancet Microbe, Vol: 1, Pages: e245-e253, ISSN: 2666-5247

BackgroundSevere COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19.MethodsIn this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients.FindingsThe median age at death of our cohort of ten patients was 73 years (IQR 52–79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight [89%] of nine patients), heart (five [56%]), and kidney (four [44%]). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two [22%] of nine patients), adrenal micro-infarction (three [33%]), pericarditis (two [22%]), disseminated mucormycosis (one [10%] of ten patients), aortic dissection (one [11%] of nine patients), and marantic endocarditis (one [11%]). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of

Journal article

Thomas SJ, Morley N, Lashen H, Naresh KN, Fernando Met al., 2020, Indolent T-Cell Lymphoproliferative Disorder of the Uterine Corpus: A Case Report, INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY, Vol: 39, Pages: 503-506, ISSN: 0277-1691

Journal article

Medani H, Elshiekh M, Naresh KN, 2020, Improving precise counting of mitotic cells in mantle cell lymphoma using phosphohistone H3 (PHH3) antibody., J Clin Pathol

AIMS: Mantle cell lymphoma (MCL) has a highly heterogeneous clinical course ranging from indolent, to aggressive and rapidly progressive disease. Proliferation is a strong predictor for disease outcome. In routine clinical practice, Ki-67 expression is used as a measure of proliferation. However, several studies have documented a high degree of inter-laboratory and inter-observer variation with Ki-67 immunohistochemistry. Phosphorylation of histone H3 occurs specifically during mitosis and hence serves as a specific marker for cells in mitosis. METHODS AND RESULTS: We investigated phosphohistone H3 (PHH3) immunohistochemistry as a proliferation maker in 28 tissue biopsies of MCL and compared the PHH3 results (as evaluated by direct microscopic visualisation and image analysis-aided scoring) with morphological subtyping, mitotic counts and Ki-67 index. We found PHH3-mitotic count was about sixfold higher than H&E-mitotic count (mitoses in 10 high power fields). Furthermore, PHH3-mitotic count in aggressive morphological variants of MCL was significantly higher than in usual MCL. The PHH3-mitotic count showed a strong linear correlation with PHH3-mitotic index (percentage positive cells). CONCLUSIONS: We found PHH3 immunohistochemistry, a reliable mitosis-specific marker, in MCL. Performing precise counts and evaluating precise proliferation indices is easier with PHH3 immunohistochemistry. This contrasts with the conventional estimation of Ki-67 percentages by 'eye-balling'.

Journal article

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

Shah V, Sherborne AL, Johnson DC, Ellis S, Price A, Chowdhury F, Kendall J, Jenner MW, Drayson MT, Owen RG, Gregory WM, Morgan GJ, Davies FE, Cook G, Cairns DA, Houlston RS, Jackson G, Kaiser MFet al., 2020, Predicting ultrahigh risk multiple myeloma by molecular profiling: an analysis of newly diagnosed transplant eligible myeloma XI trial patients, LEUKEMIA, Vol: 34, Pages: 3091-3096, ISSN: 0887-6924

Journal article

Medani H, Elshiekh M, Naresh K, 2020, Accurate Mitotic Counts in Mantle Cell Lymphoma Using Phosphohistone H3 (PHH3) Immunohistochemistry, 109th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP), Publisher: SPRINGERNATURE, Pages: 1346-1347, ISSN: 0893-3952

Conference paper

Medani H, Sayed A, Cooper N, Naresh Ket al., 2020, Bone Marrow Trephine Biopsy in Patients of Primary Immune Thrombocytopenia on Treatment with Thrombopoietin Receptor Agonists, 109th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP), Publisher: NATURE PUBLISHING GROUP, Pages: 1348-1348, ISSN: 0023-6837

Conference paper

Medani H, Sayed A, Cooper N, Naresh Ket al., 2020, Bone Marrow Trephine Biopsy in Patients of Primary Immune Thrombocytopenia on Treatment with Thrombopoietin Receptor Agonists, 109th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP), Publisher: SPRINGERNATURE, Pages: 1348-1348, ISSN: 0893-3952

Conference paper

Medani H, Elshiekh M, Naresh K, 2020, Accurate Mitotic Counts in Mantle Cell Lymphoma Using Phosphohistone H3 (PHH3) Immunohistochemistry, 109th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP), Publisher: NATURE PUBLISHING GROUP, Pages: 1346-1347, ISSN: 0023-6837

Conference paper

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

Bewicke-Copley F, Korfi K, Araf S, Kumar EA, Cummin TEC, Ashton-Key M, Barrans S, Van Hoppe S, Burton C, Elshiekh M, Rule S, Crosbie N, Clear AJ, Calaminici M, Scott DW, Rimsza LM, Geetha M, Sha C, Bentley MA, Nagano A, Davies A, Painter D, Smith A, Gribben JG, Naresh K, Westhead DR, Okosun J, Johnson P, Wang J, Fitzgibbon Jet al., 2019, Longitudinal Analyses of Diagnostic-Relapse Biopsies of Diffuse Large B Cell Lymphoma Reveal a Poor Risk Subset of ABC Patients Based on the Expression of a 30 Gene Panel, BLOOD, Vol: 134, ISSN: 0006-4971

Journal article

Li X, Kositsky R, Reddy A, Love C, Naresh K, Koff JL, Nystrand I, Leppa S, Pasanen A, Karjalainen-Lindsberg M-L, Dunkel J, Kovanen P, Qin Q, Bhagat G, Leeman-Neill RJ, Goswami RS, Wildeman S, Delabie J, Burack R, Evans AG, Amador C, Yuan J, Qureishi HN, Li S, Xu J, Yin CC, Gang AO, Norgaard PH, Pedersen MO, Chan JY, Cheah DMZ, Ong SY, Cheng CL, Lee L, Paulua F, Ondrejka SL, Hsi ED, Czader M, Wang L, Landis A, Churnetski MC, Jaye DL, Flowers CR, McCall CM, Neff J, McKinney MS, Fedoriw Y, Powers E, Montgomery ND, Bogusz AM, Hintz AS, Kovach AE, Reddy N, Arildsen MAT, Mason EF, Juskevicius R, Choi W, Au-Yeung R, Tse E, Sarno V, Chadburn A, Lopez R, Chapman JR, Behdad A, Goldschmidt N, Goodlad J, Burton C, Pillai R, Louissaint A, Soliman DS, Panea R, Dave T, Xiong B, Smith E, Dave Set al., 2019, Whole Exome and Transcriptome Sequencing in 1042 Cases Reveals Distinct Clinically Relevant Genetic Subgroups of Follicular Lymphoma, BLOOD, Vol: 134, ISSN: 0006-4971

Journal article

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

Elliott T, Simpson J, Naresh KN, Lockwood D, Bailey ACet al., 2019, An unusual case of post-kala-azar dermal leishmaniasis in a patient with HIV and visceral leishmaniasis co-infection, INTERNATIONAL JOURNAL OF STD & AIDS, Vol: 30, Pages: 1221-1223, ISSN: 0956-4624

Journal article

Khan M, Naresh K, Krell J, Diamond E, Borysiewicz Cet al., 2019, A challenging case of indeterminate cell histiocytosis with only partial response treatment., 16th International Workshop on Langerhans Cells (LC), Publisher: WILEY, Pages: 18-19, ISSN: 0014-2980

Conference paper

Hanley BP, Naresh KN, 2019, Evolution of Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma, 12th Joint Meeting of the British-Division-of-the-International-Academy-of-Pathology and the Pathological-Society-of-Great-Britain-and-Ireland (Leeds Pathology), Publisher: WILEY, Pages: S42-S42, ISSN: 0022-3417

Conference paper

Elshiekh M, Lippert T, Dalla Pria A, Bower M, Naresh Ket al., 2019, PDL1 and PDL2 Expression in Plasmablastic and Primary Effusion Lymphomas, 12th Joint Meeting of the British-Division-of-the-International-Academy-of-Pathology and the Pathological-Society-of-Great-Britain-and-Ireland (Leeds Pathology), Publisher: WILEY, Pages: S18-S18, ISSN: 0022-3417

Conference paper

Gan A, Naresh K, Diamond E, Borysiewicz Cet al., 2019, Two cellular populations occurring simultaneously in a patient with recurrent self-resolving skin lesions: Indeterminate cell histiocytosis and a previously undescribed population of small eosinophilic cells, 16th International Workshop on Langerhans Cells (LC), Publisher: WILEY, Pages: 16-16, ISSN: 0014-2980

Conference paper

El-Sharkawi D, Sharma S, Cook L, Hanley B, Johnston R, Arasaretnam A, Lazana I, Greaves P, Parkinson A, Peng Y, Kassam S, Peacock V, Kaczmarski R, Bower M, Cheung B, DeLord C, Cross M, Vroobel K, Wotherspoon A, Aldridge F, Khwaja J, Sharma B, Cwynarski K, Pettengell R, Chau I, Cunningham D, Naresh K, Iyengar S, Lindsay Set al., 2019, Comparison of Outcomes Between Patients with MYC Rearranged DLBCL and Double/Triple Hit High-Grade B-Cell Lymphoma: A Pan-London Retrospective Review, Publisher: CIG MEDIA GROUP, LP, Pages: S248-S248, ISSN: 2152-2650

Conference paper

Hanley B, Nesr G, Yebra-Fernandez E, Brown L, Rabitsch A, Killeen N, Claudiani S, Milojkovic D, Kanfer E, Apperley J, Naresh KNet al., 2019, T-cell prolymphocytic leukaemia in a patient with chronic myeloid leukaemia receiving nilotinib: first documented report, JOURNAL OF CLINICAL PATHOLOGY, Vol: 72, Pages: 511-512, ISSN: 0021-9746

Journal article

Xu D, Claudiani S, Naresh K, Mucklow S, Neelakantan P, Yebra E, Apperley JF, Khorashad J, Milojkovic Det al., 2019, Blast crisis of chronic myeloid leukemia with plasmacytoid dendritic cell phenotype associated with a rare fusion transcript, e13a3 BCR-ABL1., Leuk Lymphoma, Pages: 1-2

Journal article

El-Sharkawi D, Sharma S, Cook L, Hanley B, Johnston R, Arasaretnam A, Lazana I, Greaves P, Parkinson A, Peng Y, Kassam S, Peacock V, Kaczmarski R, Bower M, Cheung B, De Lord C, Cross M, Vroobel K, Wotherspoon A, Aldridge F, Khwaja J, Sharma B, Cwynarski K, Pettengell R, Chau I, Cunningham D, Naresh K, Iyengar Set al., 2019, COMPARISON OF OUTCOMES BETWEEN PATIENTS WITH MYC REARRANGED DLBCL AND DOUBLE/ TRIPLE HIT HIGH-GRADE B CELL LYMPHOMA: A PAN-LONDON RETROSPECTIVE REVIEW, Hematological Oncology, Vol: 37, Pages: 348-349, ISSN: 0278-0232

Journal article

Korfi K, Araf S, Bewicke-Copley F, Kumar E, Cummin T, Ashton-Key M, Barrans S, Van Hoppe S, Burton C, Elshiekh M, Rule S, Crosbie N, Clear A, Calaminici M, Menon G, Sha C, Bentley M, Nagano A, Davies A, Painter D, Smith A, Okosun J, Gribben J, Naresh KN, Westhead D, Wang J, Johnson P, Fitzgibbon Jet al., 2019, LONGITUDINAL ANALYSES OF DIAGNOSTIC-RELAPSE BIOPSIES OF DIFFUSE LARGE B CELL LYMPHOMA SUGGEST THAT RELAPSE IS MEDIATED BY DISTINCT MECHANISMS IN ABC AND GCB LYMPHOMA, Hematological Oncology, Vol: 37, Pages: 142-143, ISSN: 0278-0232

Journal article

Granai M, Ambrosio MR, Akarca A, Mundo L, Vergoni F, Santi R, Mancini V, di Stefano G, Amato T, Bellan C, Puccini B, Sorrentino E, Naresh KN, Leoncini L, Marafioti T, Lazzi Set al., 2019, Role of Epstein-Barr virus in transformation of follicular lymphoma to diffuse large B-cell lymphoma: a case report and review of the literature, HAEMATOLOGICA, Vol: 104, Pages: E269-E273, ISSN: 0390-6078

Journal article

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