PostDoc Project: SFRH/BPD/70718/2010

Systems Biology approach to unravel the molecular mechanisms involved in T-Cell Acute Lymphoblastic Leukaemia.


Summary

T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive malignancy of thymocytes induced by the transformation of T-cell progenitors and is diagnosed primarily in children and adolescents. Leukaemic transformation of immature thymocytes is caused by multistep pathogenesis, driven by a number of oncogenic mutations. Although treatment outcome in patients with T-ALL has improved in recent years, significant questions have remained to be addressed, including understanding of the factors and molecular pathways that contribute to the malignant behavior of T-ALL and how these could be used for optimization of therapies. The aim of my work is to achieve a better understanding of T-ALL by combining a computational systems biology approach with experimental validations. The computational approach is based on the construction and in-depth analysis of molecular interaction networks linking T-ALL associated genes and pathways. Here, I will first identify genes involved in T-ALL through extensive literature review. Next, they will be mapped onto the protein-protein interaction networks placing these genes to obtain the molecular context of T-ALL tumourigenesis. Importantly, selected candidate genes from computational analyses will be subsequently experimentally characterized in different T-ALL model systems. The result of this type of analysis may also provide molecular markers useful for therapeutic intervention in T-ALL.



Postdoc Fellowship


Supervisors




Publications

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)