Contakt

Das Viswanath M.Sc., Ph.D.

Phone: +420 585 632 243
Groups: LEM, Staff, Postdoctoral Fellow

Postdoctoral training

Three-dimensional culture of cancer cells for screening of potential anticancer agents .

Three-dimensional (3D) cultures of cancer cells are increasingly being recognized as physiologically-relevant in vitro tumor models. My current research is focused on the use of 3D cultures of cancer cells for effective characterization of anticancer compounds.

About me

RESEARCH INTERESTS

 

Tau aggregation in Alzheimer’s disease (AD) was believed to be an autonomous cell disorder for several years, and the events leading up to the formation of tau tangles were thought to be confined within the affected cells. However, the spread of tau aggregates from one region of the brain to the other gave the notion of prion-like spreading of tau pathology within the AD brain. I am interested in mechanisms of tau spreading and identifying druggable targets that confer a selective advantage to tau misfolding and aggregation in AD, and other related tauopathies. Additionally, I am also interested in the role of MAP/microtubule affinity-regulating kinases (MARK) in tau hyperphosphorylation. We are particularly interested in small molecule inhibitors of MARKs.

 

Three-dimensional cell cultures are physiologically-relevant in vitro tumor models with an important role in translation research. They are becoming increasingly popular biological intermediate models in cancer drug discovery and development. 3D cultures closely mimic the characteristics of in vivo tumors, in addition to recapitulating the physiologically-relevant cellular drug responses seen in tumor sub-regions. Interestingly, not only 3D cultures but cells derived from them also retain a number of tumor microenvironment-induced traits following the reversal to 2D culture. I also continue to work on my previous postdoctoral project at IMTM, which is focused on the use of 3D cultures of cancer cells for the effective characterization of anticancer compounds. 

 

Current research lines:

 

Tauopathies, tau aggregation, and spreading

Anti-cancer drugs, drugs repurposing

3D in vitro tumor models, drug resistance.

 

Publications:

 

  1. Miller JH, Das V. Potential for Treating Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules. Curr. Pharm. Des. Accepted. April 2020. 
  2. Gruner B#, Brynda J#, Das V#, Sicha V#, Stepankova J, Nekvinda J, Holub J, Pospisilova K, Fabry M, Pachtl P, Král V, Kugler M, Masek V, Medvedikova M, Matějková S, Nova A, Lišková B, Gurská S, Džubák P, Hajdúch M, Řezáčová P. Metallacarborane sulfamides: unconventional, specific, and highly selective inhibitors of carbonic anhydrase IX. J Med Chem. 2019 Sep 30. doi: 10.1021/acs.jmedchem.9b00945. (#equal contribution)
  3. K Agrawal#, V Das#, N Táborská, J Gurský, P Džubák, and M Hajdúch. Differential regulation of methylation-regulating enzymes by senescent stromal cells drives colorectal cancer cell response to DNA epi-drug decitabine. Stem Cells Internationals. 2018:6013728. (#equal contribution)
  4. K Agrawal, V Das, P Vyas, and M Hajdúch. Nucleosidic DNA demethylating epigenetic drugs – A comprehensive review from discovery to clinic. Pharmacology and Therapy. 2018, 188:45-79.
  5. J Řehulka, N Narendran, I Frydrych, P Džubák, JH Miller, M Hajdúch, and V Das. Peloruside A Induced Cell Death in Hypoxia Is p53 Dependent in HCT116 Colorectal Cancer Cells. Journal of Natural Products. 2018, 81:634-640.
  6. J Řehulka, N Annadurai, I Frydrych, P Znojek, P Džubák, P Northcote, JH Miller, M Hajdúch, and V Das. Cellular effects of microtubule-targeting agent peloruside A in hypoxia-conditioned colorectal carcinoma cells. Biochimca et Biophysica Acta. 2017, 1861:1833-1843.
  7. N Annadurai, K, Agrawal, P Džubák, M Hajdúch, and V Das. Microtubule-affinity regulating kinase is an emerging drug target candidate for Alzheimer’s disease therapy. Cellular and Molecular Life Sciences. 2017, 74:4159-4169.
  8. V Das, T Fürst, S Gurská, P Džubák, and M Hajdúch. Evaporation-reducing culture condition increases the reproducibility of multicellular spheroid formation in microtiter plates. Journal of Visualized Experiments. 2017:55403.
  9. K Agrawal#, V Das#, M Otmar, M Krečmerová, P Džubák, and M Hajdúch. Cell-based DNA demethylation detection system for screening of epigenetic drugs in 2D, 3D and xenograft models. Cytometry A. 2016, 91:133-143. (#equal contribution)
  10. V Das, T Fürst, S Gurská, P Džubák, and M Hajdúch. Reproducibility of uniform spheroids formation in 384-well plates: The effect of medium evaporation. Journal of Biomolecular Screening. 2016, 21:923-30.
  11. V Das, F Bruzzese, P Konečný, F Iannnelli, A Budillon, and M Hajdúch. Pathophysiologically-relevant in vitro tumor models for screening of anticancer compounds. Drug Discovery Today. 2015, 20:848-55.
  12. V Das, J Štěpánková, M Hajdúch, and JH Miller. Role of tumor hypoxia in acquisition of resistance to microtubule-stabilizing drugs. Biochimica Biophysica Acta. 2015, 1855:172-182.
  13. V Das, A Kanakkanthara, A Chan, and JH Miller. Potential role of tubulin tyrosine ligase-like enzymes in tumorigenesis and cancer cell resistance. Cancer Letters. 2014, 350:1-4.
  14. V Das, DA Sim, and JH Miller. Effect of taxoid and non-taxoid site microtubule-stabilizing agents on axonal transport of mitochondria in untransfected and ECFP-htau40-transfected rat cortical neurons in culture. Journal of Neuroscience Research. 2014, 92:1155-1166.
  15. SS Madhukar, A Solomon, AK Kumar, V Das, and S Krupanidhi. In silico design of inhibitors for β-secretase: Implications for Alzheimer’s disease. Current Trends in Biotechnology and Pharmacy. 2013, 7:558-566.
  16. V Das and JH Miller. Non-taxoid site microtubule-stabilizing drugs work independently of tau overexpression in mouse N2a neuroblastoma cells. Brain Research. 2012, 1489:121–132.
  17. V Das and JH Miller. Microtubule stabilization by peloruside A and paclitaxel rescues degenerating neurons from okadaic acid-induced tau phosphorylation. European Journal of Neuroscience. 2012, 35:1705-1717.

Book chapters:

 

  1. V Das and JH Miller. Microtubules as a potential therapeutic target for the treatment of neurodegenerative diseases, Yamamoto, H. and Oshiro, A. (Eds.), In: Axons: Cell Biology, Molecular Dynamics and Roles in Neural Repair and Rehabilitation, Nova Science Publishers Inc., 400 Oser Avenue, Suite 1600, Hauppauge, NY 11788. Chapter 5, pp: 281-313, 2015. (ISBN: 978-1-62948-051-0).

 

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