ZMB member Basant Kumar Thakur

ZMB Member
Basant Kumar Thakur

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Basant Kumar Thakur portrait
© B.K. Thakur

PD Dr. Basant Kumar Thakur

Department of Pediatrics III
University Hospital Essen
Hufelandstr. 55
45122 Essen

Research Overview

My working group focusses on three key aspects of extracellular vesicles (EV) summarized in the graphical abstract and explained below:

  1. Identification, purification and characterization of cancer-specific EV carrying the majority of dsDNA with clinical biomarker and functional utility.
  2. Mechanism(s) of EV dsDNA transfer into the recipient cells.
  3. Functional consequence of EV dsDNA transfer into recipient cells on metastatic cancer progression.
Basant Kumar Thakur research
© B.K. Thakur

Identification and purification of cancer specific EV carrying the majority of dsDNA with clinical biomarker and functional utility
In this project, we aim to dissect the heterogeneity of EVs derived from the mixture of healthy and cancerous cells in the blood plasma of cancer patients in order to obtain EVs with high biomarker potential and functional relevance. We believe that EV surface marker immune capturing-based techniques to enrich DNA-containing EV-subpopulations will further increase the sensitivity of mutational analysis. Using pediatric AML model in collaboration with (Prof. Dr. Bernd Giebel, Transfusion Medicine, UK Essen) we have now established bead based capturing method to isolate and analyze homogenous EV population. Characterization of homogenous leukemia EVs revealed enrichment of leukemia specific mutations in homogenous EV captured by bead capturing. In the next step, we are analyzing a large cohort of pediatric AML and healthy plasma samples for establishing EV DNA based biomarker for minimum residual disease primary responsible for relapse in pediatric patients.

Mechanism of EV dsDNA transfer into the recipient cells
Besides establishing the diagnostic potential of dsDNA in cancer EVs, our lab aims to investigate the mechanism by which tumor EV dsDNA (EV-DNA) is untaken by the healthy recipient cells in the pre-metastatic niche. Key topics related to the study are (i) to understand the molecular pathways explored by the cancer EVs to introduce the DNA inside the recipient cells and (ii) the communication of EV-DNA with the intracellular organelle inside the recipient cells. Detailed functional characterization of the molecular machinery involved in the EV-DNA uptake by distant recipient cells and the interaction of EV-DNA with the cytoplasmic and nuclear components of these recipient cells in the tumor microenvironment will improve our understanding on the biology of cancer metastasis.

Functional consequence of EV dsDNA transfer in recipient cells on metastatic cancer progression
Our data indicating the uptake of EV-DNA by the recipient cells motivates us to explore the function of EV-DNA in pre-metastatic niche immuno-modulation. Our working hypothesis is that EV-DNA modulates immune cell response and can influence the distant metastatic cells towards pro-inflammation. Indeed, our preliminary data suggest the activation of the cytosolic DNA-sensing pathway cGAS/STING (cyclic GMP-AMP synthase—stimulator of interferon genes), resulting in cell cycle arrest or apoptosis in lung fibroblast cells when educated with breast cancer-derived EV-DNA. We believe that increased EV-DNA production by cancer cells and its uptake by immune cells, like dendritic cells in circulation, lead to activation of cGAS/STING signaling. These activated dendritic cells when recruited to the cells in the pre-metastatic niche can induce the whole circuit of inflammatory pathways potentially responsible for the recruitment of tumor cells to the distant organ in the process of metastasis.
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Selected Publications

    Journal articles

  • Zhu, Xingfu; Chen, Qiang; Zhao, Hao; Yang, Qiqi; Goudappagouda, None; Gelléri, Márton; Ritz, Sandra; Ng, David; Koynov, Kaloian; Parekh, Sapun H.; Chetty, Venkatesh Kumar; Thakur, Basant Kumar; Cremer, Christoph; Landfester, Katharina; Müllen, Klaus; Terenzio, Marco; Bonn, Mischa; Narita, Akimitsu; Liu, Xiaomin
    Intrinsic Burst-Blinking Nanographenes for Super-Resolution Bioimaging
    In: Journal of the American Chemical Society: JACS Vol. 146 (2024) Nr. 8, pp. 5195 - 5203
  • Chetty, Venkatesh Kumar; Ghanam, Jamal; Lichá, Kristína; Brenzel, Alexandra; Reinhardt, Dirk; Thakur, Basant Kumar
    Y-box binding protein 1 in small extracellular vesicles reduces mesenchymal stem cell differentiation to osteoblasts : implications for acute myeloid leukaemia
    In: Journal of Extracellular Vesicles (JEV) Vol. 13 (2024) Nr. 3, e12417
  • Ghanam, Jamal; Chetty, Venkatesh Kumar; Anchan, Srishti; Reetz, Laura; Yang, Qiqi; Rideau, Emeline; Liu, Xiaomin; Lieberwirth, Ingo; Wrobeln, Anna; Hoyer, Peter; Reinhardt, Dirk; Thakur, Basant Kumar
    Extracellular vesicles transfer chromatin-like structures that induce non-mutational dysfunction of p53 in bone marrow stem cells
    In: Cell Discovery Vol. 9 (2023) Nr. 1, 12
  • Ghanam, Jamal; Chetty, Venkatesh Kumar; Zhu, Xingfu; Liu, Xiaomin; Gelléri, Márton; Barthel, Lennart; Reinhardt, Dirk; Cremer, Christoph; Thakur, Basant Kumar
    Single Molecule Localization Microscopy for Studying Small Extracellular Vesicles
    In: Small Vol. 19 (2023) Nr. 12, 2205030
  • Jennrich, Sara; Pelzer, Martin; Tertel, Tobias; Koska, Benjamin; Vüllings, Melanie; Thakur, Basant Kumar; Jendrossek, Verena; Timmermann, Beate; Giebel, Bernd; Rudner, Justine
    CD9- and CD81-positive extracellular vesicles provide a marker to monitor glioblastoma cell response to photon-based and proton-based radiotherapy
    In: Frontiers in Oncology Vol. 12 (2022) 947439
  • Ghanam, Jamal; Chetty, Venkatesh Kumar; Barthel, Lennart; Reinhardt, Dirk; Hoyer, Peter Friedrich; Thakur, Basant Kumar
    DNA in extracellular vesicles : From evolution to its current application in health and disease
    In: Cell and Bioscience Vol. 12 (2022) Nr. 1, 37
  • Chetty, Venkatesh Kumar; Ghanam, Jamal; Anchan, Srishti; Reinhardt, Katarina; Brenzel, Alexandra; Gelléri, Márton; Cremer, Christoph; Grueso-Navarro, Elena; Schneider, Markus; von Neuhoff, Nils; Reinhardt, Dirk; Jablonska, Jadwiga; Nazarenko, Irina; Thakur, Basant Kumar
    Efficient Small Extracellular Vesicles (EV) Isolation Method and Evaluation of EV-Associated DNA Role in Cell–Cell Communication in Cancer
    In: Cancers Vol. 14 (2022) Nr. 9, 2068
  • Jablonska, Jadwiga; Rist, Malwina; Spyra, Ilona; Tengler, Luisa; Domnich, Maksim; Kansy, Benjamin; Giebel, Bernd; Thakur, Basant Kumar; Rotter, Nicole; Lang, Stephan; Ludwig, Sonja
    Evaluation of Immunoregulatory Biomarkers on Plasma Small Extracellular Vesicles for Disease Progression and Early Therapeutic Response in Head and Neck Cancer
    In: Cells Vol. 11 (2022) Nr. 5, 902
  • Barthel, Lennart; Hadamitzky, Martin; Dammann, Philipp; Schedlowski, Manfred; Sure, Ulrich; Thakur, Basant Kumar; Hetze, Susann
    Glioma : molecular signature and crossroads with tumor microenvironment
    In: Cancer and Metastasis Reviews Vol. 41 (2022) pp. 53 - 75
  • Kontopoulou, Evangelia; Strachan, Sarah; Reinhardt, Katarina; Kunz, Fabienne; Walter, Christiane; Walkenfort, Bernd; Jastrow, Holger; Hasenberg, Mike; Giebel, Bernd; von Neuhoff, Nils; Reinhardt, Dirk; Thakur, Basant Kumar
    Evaluation of dsDNA from extracellular vesicles (EVs) in pediatric AML diagnostics
    In: Annals of Hematology Vol. 99 (2020) Nr. 3, pp. 459 - 475
  • Bruer, Marius; Reinhardt, Dirk; Welte, Karl; Thakur, Basant Kumar
    Insights into the limitations of transient expression systems for the functional study of p53 acetylation site and oncogenic mutants
    In: Biochemical and Biophysical Research Communications (BBRC) Vol. 524 (2020) Nr. 4, pp. 990 - 995
  • Droste, Marvin; Thakur, Basant Kumar; Eliceiri, Brian P.
    Tumor-Derived Extracellular Vesicles and the Immune System : Lessons From Immune-Competent Mouse-Tumor Models
    In: Frontiers in Immunology Vol. 11 (2020) pp. 606859
  • Kosnopfel, Corinna; Sinnberg, Tobias; Sauer, Birgit; Niessner, Heike; Muenchow, Alina; Fehrenbacher, Birgit; Schaller, Martin; Mertens, Peter R.; Garbe, Claus; Thakur, Basant Kumar; Schittek, Birgit
    Tumour progression stage-dependent secretion of yb-1 stimulates melanoma cell migration and invasion
    In: Cancers Vol. 12 (2020) Nr. 8, pp. 1 - 17
  • Jablonska, Jadwiga; Pietrowska, Monika; Ludwig, Sonja; Lang, Stephan; Thakur, Basant Kumar
    Challenges in the Isolation and Proteomic Analysis of Cancer Exosomes : Implications for Translational Research
    In: Proteomes Vol. 7 (2019) Nr. 2, 22
  • Kunz, Fabienne; Kontopoulou, Evangelia; Reinhardt, Katarina; Soldierer, Maren; Strachan, Sarah; Reinhardt, Dirk; Thakur, Basant Kumar
    Detection of AML-specific mutations in pediatric patient plasma using extracellular vesicle–derived RNA
    In: Annals of Hematology Vol. 98 (2019) Nr. 3, pp. 595 - 603
  • Pylaeva, Ekaterina; Harati, Mozhgan Dehghan; Spyra, Ilona; Bordbari, Sharareh; Strachan, Sarah; Thakur, Basant Kumar; Höing, Benedikt; Franklin, Cindy; Skokowa, Julia; Welte, Karl; Schadendorf, Dirk; Bankfalvi, Agnes; Brandau, Sven; Lang, Stephan; Jablonska, Jadwiga
    NAMPT signaling is critical for the proangiogenic activity of tumor-associated neutrophils
    In: International Journal of Cancer Vol. 144 (2019) Nr. 1, pp. 136 - 149
  • Sansone, Pasquale; Savini, Claudia; Kurelac, Ivana; Chang, Qing; Amato, Laura Benedetta; Strillacci, Antonio; Stepanova, Anna; Iommarini, Luisa; Mastroleo, Chiara; Daly, Laura; Galkin, Alexander; Thakur, Basant Kumar; Soplop, Nadine; Uryu, Kunihiro; Hoshinob, Ayuko; Norton, Larry; Bonafé, Massimiliano; Cricca, Monica; Gasparre, Giuseppe; Lyden, David; Bromberg, Jacqueline
    Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 114 (2017) Nr. 43, pp. E9066 - E9075
  • Becker, Annette; Thakur, Basant Kumar; Weiss, Joshua Mitchell; Kim, Han Sang; Peinado, Héctor; Lyden, David
    Extracellular Vesicles in Cancer : Cell-to-Cell Mediators of Metastasis
    In: Cancer Cell Vol. 30 (2016) Nr. 6, pp. 836 - 848