Biology

Professor Ashok Venkitaraman
Medical Research Council Cancer Unit, University of Cambridge, UK

Transition from the pre-malignant to invasive stages of cancer progression in epithelial tissues is accompanied by the inactivation of tumour suppressive mechanisms that control genome stability. I will discuss insights emerging from our lab’s work concerning the cellular and molecular organization of these tumour suppressive mechanisms (eg., 1-4), and new approaches (eg., 5-7) that offer the potential for early clinical intervention through improvements in risk stratification, diagnosis and therapy.

Selected references

1. Venkitaraman, A.R. (2014) Cancer suppression by the chromosome custodians, BRCA1 and BRCA2. Science. 343(6178):1470-5.

2. Wickramasinghe, V., Savill, J., Chavali, S., Jonsdottir, A.B., Rajendra, E., Gruner, T., Laskey, R., Babu, M., & Venkitaraman, A.R. (2013) Human inositol             phosphate multikinase regulates transcript-selective nuclear mRNA export to preserve genome integrity.  Molecular Cell 51, 737-50.

3. Jeyasekharan, A.D., Liu, Y., Hattori, H., Pisupati, V., Jonsdottir, A.B., Rajendra, E., Lee, M., Sundaramoorthy, E., Schlachter, S., Kaminski, C., Rosenfeld, Y.,             Sato, K., Savill, J., Ayoub, N. &           Venkitaraman, A.R. (2013). A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling       localization. Nature Str Mol Biol. 20, 1191-8.

4. Wickramasinghe V, Gonzàlez-Porta M, Perera D, Bartolozzi AR, Sibley CR, Hallegger M, Ule J, Marioni JC, Venkitaraman AR. (2015). Regulation of constitutive      and alternative mRNA splicing across the human transcriptome by PRPF8 is determined by 5' splice site strength. Genome Biol 16(1):201-7.

5. Laraia L, McKenzie G, Spring DR, Venkitaraman AR, Huggins DJ. (2015). Overcoming Chemical, Biological, and Computational Challenges in the Development   of Inhibitors Targeting Protein-Protein Interactions. Chemistry & Biol. 22(6):689-703.

6. Liang, H., Esposito, A., Collin, P., Surana, U. & Venkitaraman, A.R. (2014). Homeostatic control of polo-like kinase-1 engenders non-genetic heterogeneity in G2       checkpoint fidelity and timing. Nature Commun. 5:4048. doi: 10.1038/ncomms5048.

7. Ibbeson BM, Laraia L, Alza E, O' Connor CJ, Tan YS, Davies HM, McKenzie G, Venkitaraman A.R., Spring D.R. (2014). Diversity-oriented synthesis as a tool for identifying new modulators of mitosis. Nature Commun. 5:3155. doi: 10.1038/ncomms4155