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Jay Vadakekolathu

Jayakumar Vadakekolathu

Research Fellow

School of Science & Technology

Staff Group(s)
Bioscience

Role

Dr Jayakumar Vadakekolathu is a Research Fellow in the John van Geest Cancer Research Centre. His research area mainly focused on understanding the tumour microenvironment (TME) at the molecular level using spatial transcriptomics and cutting edge high throughput platforms. He also studies how the interactions of tumour, stromal and immune cells at TME create a permissive microenvironment for tumour immune evasion and metastasis. Dr Vadakekolathu is also responsible for managing the NanoString GeoMx® Digital spatial profiling system, NanoString nCounter® FLEX Analysis System, Agilent Microarray Gene Expression and 10x Chromium Single Cell gene expression platforms in the John van Geest Cancer Research Centre.

Career overview

Dr Vadakekolathu obtained an MSc (Biotechnology) from Bharathidasan University (1999-2001), Tiruchirappalli, TN, India. After his Master's, he worked as a Senior Research Fellow at the Indian Institute of Spices Research (IISR), Calicut, Kerala, India for 5 years. He then obtained MRes In Advanced Genomics and Proteomics Sciences (AGPS) which was jointly provided by The University of Nottingham and Nottingham Trent University (2008-2009). He subsequently completed his PhD in Cancer Immunology at Nottingham Trent University (NTU) under the direction of Professor Robert C Rees in 2014. Since 2014, Dr Vadakekolathu has been working as a Research Fellow in the John van Geest Cancer Research Centre on various projects led by Professor Sergio Rutella.

Research areas

Current research involves understanding tumour microenvironments of acute myeloid leukaemia and breast cancer under the leadership of Prof Sergio Rutella. Using the state of the art GeoMx spatial profiling combined with Illumina next-generation sequencing and nCounter flex analysis system, we are trying to understand the tumour ecosystem in detail using real-world patient samples. So far, we have completed pan-cancer immune profiling of 500 bone marrow samples from adults and children diagnosed with AML collected at various collaborative institutes in Europe and US (University of Sheffield; Princess Margaret Cancer Centre, Toronto; Children's Hospital of Philadelphia; Technische Universität Dresden and the University of Regensburg, Germany). We are also studying the role of mutated TP53 in AML and how the mutations influences immune infiltration and treatment outcome. Several cell line models of AML were created in the lab for understanding the mechanistic of these interactions using mixed lymphocyte cultures and high-throughput analytical platforms.

In breast cancer, we are conducting spatial profiling of triple-negative breast cancer (TNBC) to understand the stromal tumour and immune cell interaction. In collaboration with the University of Nottingham, we have profiled 400 breast cancer samples as a part of a biomarker discovery project. We have also identified a group of protein methyltransferases (PMTs) in regulating epithelial-mesenchymal transition (EMT), invasion, and migration in breast cancer cell models. The expression of these PMTs is often regulated by inflammatory cytokines/adipokines such as interferon-gamma, TNF-Alpha and interleukin-6. Activation of these PMTs in adipose-rich tumours correlated with poor overall and relapse-free survival in patients with breast cancer. High throughput transcriptome and proteome studies combined with a range of functional assays have confirmed their role in global epigenetic alterations. Current studies are focused on understanding mechanisms involved in the activation of these PMTs in TME and its targeting using small molecule inhibitors.  Apart from this, several spatial biology and single-cell transcriptomic projects are ongoing to further understand the biology of breast and other cancer TME such as colorectal, Lymphoma and Gastric cancers.

Publications

Research  Articles

  1. Corradi G, Bassani B, Simonetti G, Sangaletti S, Vadakekolathu J, Fontana MC, Pazzaglia M, Gulino A, Tripodo C, Cristiano G, Bandini L, Ottaviani E, Ocadlikova D, Piccioli M, Martinelli G, Colombo MP, Rutella S, Cavo M, Ciciarello M, Curti A. Release of IFN-γ by acute myeloid leukemia cells remodels bone marrow immune microenvironment by inducing regulatory T cells. Clin Cancer Res. 2022 Mar 29: clincanres.3594.2021. doi: 10.1158/1078-0432.CCR-21-3594.
  2. Ferri C, Di Biase A, Bocchetti M, Zappavigna S, Wagner S, Le Vu P, Luce A, Cossu AM, Vadakekolathu J, Miles A, Boocock DJ, Robinson A, Schwerdtfeger M, Tirino V, Papaccio F, Caraglia M, Regad T, Desiderio V. MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer. J Exp Clin Cancer Res. 2022 Jan 11;41(1):20.
  3. Yau TO, Vadakekolathu J, Foulds GA, Du G, Dickins B, Polytarchou C, Rutella S. Hyperactive neutrophil chemotaxis contributes to anti-tumor necrosis factor-α treatment resistance in inflammatory bowel disease. J Gastroenterol Hepatol. 2022 Mar;37(3):531-541.
  4. Howard FHN, Al-Janabi H, Patel P, Cox K, Smith E, Vadakekolathu J, Pockley AG, Conner J, Nohl JF, Allwood DA, Collado-Rojas C, Kennerley A, Staniland S, Muthana M. Nanobugs as Drugs: Bacterial Derived Nanomagnets Enhance Tumor Targeting and Oncolytic Activity of HSV-1 Virus. Small. 2022 Jan 25:e2104763.
  5. Ragaini S, Wagner S, Marconi G, Parisi S, Sartor C, Nanni J, Cristiano G, Talami A, Olivi M, Ocadlikova D, Ciciarello M, Corradi G, Ottaviani E, Papayannidis C, Paolini S, Vadakekolathu J, Cavo M, Rutella S, Curti A. An IDO1-related immune gene signature predicts overall survival in acute myeloid leukemia. Blood Adv. 2022 Jan 11;6(1):87-99.
  6. IL-1B drives opposing responses in primary tumours and bone metastases; harnessing combination therapies to improve outcome in breast cancer" Tulotta C, Lefley D, Moore C, Amariutei A, Spicer A, Quayle L, Hughes R, Ahmed K, Cookson V, Evans C, Vadakekolathu J, Heath P, Francis S, Pinteaux E, Pockley A and Ottewell P. NPJ Breast Cancer. 2021 Jul 21;7(1):95.
  7. Almshayakhchi R, Nagarajan D, Vadakekolathu J, Guinn B A, Reeder S, Brentville V, Metheringham R, Pockley A. G, Durrant L, McArdle S. A Novel HAGE/WT1-ImmunoBody® Vaccine Combination Enhances Anti-Tumour Responses When Compared to Either Vaccine Alone. Frontiers in Oncology. 2021 Jun;11: 2086.
  8. Zhou Q, Vadakekolathu J, Watad A, Sharif K, Russell T, Rowe H, Khan A, Millner PA, Loughenbury P, Rao A, Dunsmuir R, Timothy J, Damiani G, Pigatto PDM, Malagoli P, Banfi G, El-Sherbiny YM, Bridgewood C, McGonagle D. SARS-CoV-2 Infection Induces Psoriatic Arthritis Flares and Enthesis Resident Plasmacytoid Dendritic Cell Type-1 Interferon Inhibition by JAK Antagonism Offer Novel Spondyloarthritis Pathogenesis Insights. Front Immunol. 2021 Apr 15;12: 635018.
  9. Kwan A, Winder N, Atkinson E, Al-Janabi H, Allen RJ, Hughes R, Moamin M, Louie R, Evans D, Hutchinson M, Capper D, Cox K, Handley J, Wilshaw A, Kim T, Tazzyman SJ, Srivastava S, Ottewell P, Vadakekolathu J, Pockley G, Lewis CE, Brown JE, Danson SJ, Conner J, Muthana M. Macrophages Mediate the Antitumor Effects of the Oncolytic Virus HSV1716 in Mammary Tumors. Mol Cancer Ther. 2021 Mar; 20(3):589-601.
  10. Uy GL, Aldoss I, Foster MC, Sayre PH, Wieduwilt MJ, Advani AS, Godwin JE, Arellano ML, Sweet KL, Emadi A, Ravandi F, Erba HP, Byrne M, Michaelis L, Topp MS, Vey N, Ciceri F, Carrabba MG, Paolini S, Huls GA, Jongen-Lavrencic M, Wermke M, Chevallier P, Gyan E, Récher C, Stiff PJ, Pettit KM, Löwenberg B, Church SE, Anderson E, Vadakekolathu J, Santaguida M, Rettig MP, Muth J, Curtis T, Fehr E, Guo K, Zhao J, Bakkacha O, Jacobs K, Tran K, Kaminker P, Kostova M, Bonvini E, Walter RB, Davidson-Moncada JK, Rutella S, DiPersio JF. Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia. Blood. 2021 Feb 11;137(6):751-762.
  11. Vadakekolathu J, Lai C, Reeder S, Church SE, Hood T, Lourdusamy A, Rettig MP, Aldoss I, Advani AS, Godwin J, Wieduwilt MJ, Arellano M, Muth J, Yau TO, Ravandi F, Sweet K, Altmann H, Foulds GA, Stölzel F, Middeke JM, Ciciarello M, Curti A, Valk PJM, Löwenberg B, Gojo I, Bornhäuser M, DiPersio JF, Davidson-Moncada JK, Rutella S. TP53 abnormalities correlate with immune infiltration and associate with response to flotetuzumab immunotherapy in AML. Blood Adv. 2020 Oct 27; 4(20):5011-5024.
  12. Vadakekolathu J, Lai C, Reeder S, Church SE, Hood T, Muth J, Altmann H, Ciciarello M, Curti A, Valk PJ, Löwenberg B, Bornhäuser M, DiPersio JF, Davidson-Moncada JK, & Rutella S. (2020). Abstract CT035: TP53 abnormalities correlate with immune infiltration and are associated with response to flotetuzumab, an investigational immunotherapy, in acute myeloid leukemia. Cancer Research, 80(16 Supplement), CT035 LP-CT035.
  13. Vadakekolathu J, Minden MD, Hood T, Church SE, Reeder S, Altmann H, Sullivan AH, Viboch EJ, Patel T, Ibrahimova N, Warren SE, Arruda A, Liang Y, Smith TH, Foulds GA, Bailey MD, Gowen-MacDonald J, Muth J, Schmitz M, Cesano A, Pockley AG, Valk PJM, Löwenberg B, Bornhäuser M, Tasian SK, Rettig MP, Davidson-Moncada JK, DiPersio JF, Rutella S. Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia. Sci Transl Med. 2020 Jun 3;12(546).
  14. Wagner S, Vadakekolathu J, Tasian SK, Altmann H, Bornhäuser M, Pockley AG, Ball GR, Rutella S. A parsimonious 3-gene signature predicts clinical outcomes in an acute myeloid leukemia multicohort study. Blood Adv. 2019 Apr 23;3(8):1330-1346.
  15. Alves R, McArdle SEB, Vadakekolathu J, Gonçalves AC, Freitas-Tavares P, Pereira A, Almeida AM, Sarmento-Ribeiro AB, Rutella S. Flow cytometry and targeted immune transcriptomics identify distinct profiles in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors with or without interferon-α. J Transl Med. 2020 Jan 3;18(1):2.
  16. Rutella S, Vadakekolathu J, Hood T, Reeder S, Warren SE, Danaher P, Davidson-Moncada J, Cesano A, Beechem JM, Tasian SK, & Minden MD. (2020). Abstract B63: Immune gene expression profiling of acute myeloid leukemia identifies predictors of survival and actionable targets for treatment. Cancer Immunology Research, 8(4 Supplement), B63 LP-B63.
  17. Ragaini S, Wagner S, Marconi G, Parisi S, Sartor C, Nanni J, Cristiano G, Talami A, Olivi M, Ocadlikova D, Ciciarello M, Corradi G, Ottaviani E, Papayannidis C, Paolini S, Vadakekolathu J, Cavo M, Rutella S & Curti A. (2019). An IDO1-Related 3-Gene Signature Predicts Overall Survival in Intermediate-Risk Acute Myeloid Leukemia. Blood, 134(Supplement_1), 5193.
  18. Biase A Di, Regad T, Vadakekolathu J, Powe D, Jäck HM, & Roth E. (2019). Abstract B152: Generation of monoclonal antibodies against a newly identified target for invasive prostate cancer and their use in the development of an antibody-based targeting therapy. Cancer Immunology Research, 7(2 Supplement), B152 LP-B152.
  19. Vadakekolathu J, Minden MD, Hood T, Church SE, Reeder S, Altmann H, Sullivan AH, Viboch E J, Patel T, Ibrahimova N, Warren SE, Arruda A, Schmitz M, Liang Y, Cesano A, Pockley AG, Valk P, Löwenberg B, Bornhäuser M & Rutella S. (2019). Immune Landscapes Predict Chemotherapy Resistance and Anti-Leukemic Activity of Flotetuzumab, an Investigational CD123×CD3 Bispecific Dart® Molecule, in Patients with Relapsed/Refractory Acute Myeloid Leukemia. Blood, 134(Supplement_1), 460.
  20. Ciciarello M, Corradi G, Sangaletti S, Bassani B, Simonetti G, Vadakekolathu J, Marconi G, Martinelli G, Colombo MP, Rutella S, Cavo M & Curti A. (2019). Interferon-γ-Dependent Inflammatory Signature in Acute Myeloid Leukemia Cells Is Able to Shape Stromal and Immune Bone Marrow Microenvironment. Blood, 134(Supplement_1), 1212.
  21. Rutella S, Church SE, Vadakekolathu J, Reeder S, Sullivan AH, Warren S, Baughman J, Muth J, Park H, Uronis H, Kang YK, Ng MCH, Enzinger P, Lee KW, Huber K, Wynter-Horton A, Li D, Bang YJ, Davidson-Moncada J, & Catenacci DV. (2019). 123P - Evaluation of tumour microenvironment identifies immune correlates of response to combination immunotherapy with margetuximab (M) and pembrolizumab (P) in HER2+ gastroesophageal adenocarcinoma (GEA). Annals of Oncology, 30, v38–v39.
  22. Park H, Uronis, H, Kang, YK, Ng MCH, Enzinger P, Lee KW, Rutella S, Church SE, Nordstrom J, Knutson K, Erskine C, Wu T, Yen J, Franovic A, Muth J, Rosales M, Vadakekolathu J, Davidson-Moncada J, Bang YJ, & Catenacci DV (2019). 1189PD - Determinants of response of HER2+ gastric cancer (GC) vs gastroesophageal junction adenocarcinoma (GEJ) to margetuximab (M) plus pembrolizumab (P) post trastuzumab (T). Annals of Oncology, 30, v485.
  23. Vadakekolathu J, Reeder S, Coveney C & Rutella S. (2019). Tipifarnib Modulates Interferon (IFN)-γ-Inducible Genes in Acute Myeloid Leukemia. Blood, 134(Supplement_1), 2726.
  24. Vadakekolathu J, Al-Juboori SIK, Johnson C, Schneider A, Buczek ME, Di Biase A, Pockley AG, Ball GR, Powe DG, Regad T. MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer. Cell Death Dis. 2018 Mar 1;9(3):344.
  25. Al-Juboori SI, Vadakekolathu J*, Idri S, Wagner S, Zafeiris D, Pearson JR, Almshayakhchi R, Caraglia M, Desiderio V, Miles AK, Boocock DJ, Ball GR, Regad T. PYK2 promotes HER2-positive breast cancer invasion. J Exp Clin Cancer Res. 2019 May 22;38(1):210.
  26. Foulds GA, Vadakekolathu J, Abdel-Fatah TMA, Nagarajan D, Reeder S, Johnson C, Hood S, Moseley PM, Chan SYT, Pockley AG, Rutella S, McArdle SEB. Immune-Phenotyping and Transcriptomic Profiling of Peripheral Blood Mononuclear Cells From Patients With Breast Cancer: Identification of a 3 Gene Signature Which Predicts Relapse of Triple Negative Breast Cancer. Front Immunol. 2018 Sep 11; 9:2028.
  27. Rutella S, Vadakekolathu J, Altmann H, Patel T, Reeder S, Liang Y, Schmitz M, Hood T, Danaher P, Warren S, Cesano A, Beechem JM, Pockley AG, Tasian SK, & Bornhäuser M. (2018). Capturing the complexity of the immune microenvironment of acute myeloid leukemia with 3D biology technology. Journal of Clinical Oncology, 36(5_suppl), 50.
  28. Balahmar RM, Boocock DJ, Coveney C, Ray S, Vadakekolathu J, Regad T, Ali S, Sivasubramaniam S. Identification and characterisation of NANOG+/ OCT-4high/SOX2+ doxorubicin-resistant stem-like cells from transformed trophoblastic cell lines. Oncotarget. 2018 Jan 11;9(6):7054-7065.
  29. Harner-Foreman N, Vadakekolathu J, Laversin SA, Mathieu MG, Reeder S, Pockley AG, Rees RC, Boocock DJ. A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics. Sci Rep. 2017 Jan 17; 7:40633.
  30. Saif JM, Vadakekolathu J, Rane SS, McDonald D, Ahmad M, Mathieu M, Pockley AG, Durrant L, Metheringham R, Rees RC, McArdle SE. Novel prostate acid phosphatase-based peptide vaccination strategy induces antigen-specific T-cell responses and limits tumour growth in mice. Eur J Immunol. 2014 Apr; 44(4):994-1004.

Review Articles

  1. Malhi SK, Saif J, Vadakekolathu J. The Twelfth International Conference on Progress in Vaccination Against Cancer (PIVAC 12), Nottingham, UK, 11-13 September 2012: insights into the dynamics of anti-tumour immunity and the development of cancer vaccines. Cancer Immunol Immunother. 2013 Aug;62(8):1431-7.
  2. Vadakekolathu J, Rutella S. T-Cell Manipulation Strategies to Prevent Graft-Versus-Host Disease in Haploidentical Stem Cell Transplantation. Biomedicines. 2017 Jun 21;5(2):33.
  3. Zafeiris D, Vadakekolathu J, Wagner S, Pockley AG, Ball GR, Rutella S. Discovery and application of immune biomarkers for hematological malignancies. Expert Rev Mol Diagn. 2017 Nov;17(11):983-1000.

Book  Chapters

  1. Vadakekolathu J, Miles AK, Boocock DJ.  and Mcardle SEB. 2014. Identification of tumor antigens for clinical evaluation. In: Tumor immunology and immunotherapy. Oxford: Oxford University Press, pp. 127-129. ISBN 9780199676866

See a full list of Dr Vadakekolathu’s publications on ORCID

Google scholar of Dr  Vadakekolathu : https://scholar.google.co.uk/citations?user=YF4qwmcAAAAJ&hl=en

See all of Jayakumar Vadakekolathu's publications...