The aim of this project was to achieve a better understanding of T-ALL by combining a computational systems biology approach with experimental validations. The computational approach was based on the construction and in-depth analysis of gene expression data and pathways. This helped to elucidate the involvement of the FoxN1 transcription factor in T-ALL (Carcinogenesis 2018). Similar gene expression analyses were applied to study the association of pseudokinease TRIB2 with melanoma (Carcinogenesis 2015) and drug responses in breast cancer (Breast Cancer Research 2014).
Cancer typically involves various processes which are interlinked. For a better understanding of its complexity, the dissection of the underlying molecular interaction networks might help (Springer 2015). Such endeavour is greatly facilitated by our extension of the UniHI database which now enables the rapid application of complex filtering and prioritization procedures to molecular interaction networks (NAR 2014). Using this resource, we could show that the mammalian circadian clock is closely linked to the cell cycle and connected to oncogenic mechanisms through protein interactions. The knowledge of these interactions might help in the further development of the so called chronotherapy of cancer (PloS Genetics 2013). .
Marinella N Ghezzo, Mónica T Fernandes, Ivette Pacheco-Leyva, Pedro M Rodrigues, Rui S Machado, Marta A S Araújo, Ravi K Kalathur, Matthias E Futschik, Nuno L Alves and Nuno R dos Santos (2018) FoxN1-dependent thymic epithelial cells promote T-cell leukemia development, Carcinogenesis 39, 12, 1463 - 1476 (pdf+html)
R. Hill, Ravi K. Kalathur, L. Colaço, R. Brandão, S. Ugurel, Matthias Futschik and W. Link (2015) TRIB2 as a biomarker for diagnosis and progression of melanoma. Carcinogenesis 36(4):469-77 (pdf + html)
R. Hill, Ravi Kalathur, S. Callejas, L. Colaço, R. Brandão, Beatriz Serelde, A. Cebriá, C. Blanco-Aparicio, J. Pastor, Matthias Futschik, A. Dopazo and W. Link (2014) A novel Phosphatidylinositol 3-Kinase (PI3K) inhibitor directs a potent FOXO-dependent, p53-independent cell cycle arrest phenotype characterized by the differential induction of a subset of FOXO-regulated genes, Breast Cancer Research 16(6):482 (pdf + html)
Miguel Hernandez-Prieto, Ravi Kalathur and Matthias E. Futschik (2014) Molecular networks, their analysis and representation, Chapter 24, 399-418, Springer Handbook of Bio- and Neuroinformatics, ed. Nik Kasabov, Springer (preprint-pdf, Book's web-page)
Ravi K. Kalathur, José P. Pinto,Miguel A. Hernández-Prieto, Rui S.R. Machado, Dulce Almeida, Gautam Chaurasia and Matthias Futschik (2014) UniHI 7: an enhanced database for retrieval and interactive analysis of human molecular interaction networks, Nucleic Acids Research, Database issue, 42 (D1): D408-D414 (html, pdf)
Thomas Wallach, Katja Schellenberg, Bert Maier, Ravi Kalathur , Pablo Porras, Erich E. Wanker, Matthias E. Futschik and Achim Kramer (2013) Dynamic Circadian Protein-Protein Interaction Networks Predict Temporal Organization of Cellular Functions, PloS Genetics , 9(3): e1003398. doi:10.1371/journal.pgen.1003398 (html, pdf)