Professor Tanja Stankovic is characterising the DNA damage response and genome instability in a range of haematological malignancies.
Professor of Cancer Genetics, School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham.
Background and Research focus
The Ataxia Telangiectasia Mutated (ATM) gene is frequently inactivated in lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and is associated with defective apoptosis in response to chemotherapeutic agents. ATM mutant cells exhibit impaired DNA double strand break repair. Her group has demonstrated that inhibition of Poly (ADP-ribose) polymerase (PARP), an enzyme essential for DNA double strand break repair, selectively sensitizes ATM-deficient tumour cells to killing. In collaboration with Dr Guy Pratt, Professor Stankovic has initiated a phase I/II clinical trial with a novel, highly specific PARP inhibitor (olaparib) in ATM null lymphoid malignancies. The Stankovic group is also interested studying the role of ATM in a wide array of human malignancies by developing murine models for ATM deficient lymphoid malignancies. Her group is also investigating the optimal strategies for targeting pro-survival pathways that confer apoptosis resistance in paediatric ALL. This has involved undertaking a wide screen of kinome and DNA repair profiles and identifying deregulated kinases and DNA repair proteins associated with apoptosis resistance. Pharmacological inhibition of these dysregulated proteins will be monitored using in vivo and in vitro models.
Cancer cell biology; clinical trials; DNA damage response and genomic instability, chronic lymphocytic leukemia, Ataxia Telangiectasia Mutated.
Professor Stankovic has published over 60 research papers in high impact peer reviewed scientific journals as well as reviews in the fields of cancer genetics and DNA damage response. Her research has been funded by the Leukaemia Research Fund, Cancer Research UK, Kay Kendall Leukaemia Fund, and CLIC. She is involved in the annual assessment of individual PhD student progress providing advice on student progress where required. Professor Stankovic also makes substantial contributions to teaching undergraduate, postgraduate and medical students. In particular, she delivers lectures on MBChB and BMedSc courses as well as MSc in Clinical Oncology. Professor Stankovic is an enthusiastic advocator of translational cancer research and gives frequent talks at both local and national meetings. Finally, she sits on several committees including the UK-CLL forum Executive Committee, European Research Initiative on CLL (ERIC), Scientific Committee of the International Workshop on ‘Ataxia Telangiectasia/ATM and Childhood Leukaemia Research UK (CLR-UK).
Da Costa D, Agathanggelou A, Perry T, Weston V, Petermann E, Zlatanou A, Oldreive C, Wei W, Stewart G, Longman J, Smith E, Kearns P, Knapp S, Stankovic T. BET inhibition as a single or combined therapeutic approach in primary paediatric B-precursor acute lymphoblastic leukaemia. Blood Cancer J. 2013 Jul 19;3:e126.
Picaud S, Da Costa D, Thanasopoulou A, Filippakopoulos P, Fish PV, Philpott M, Fedorov O, Brennan P, Bunnage ME, Owen DR, Bradner JE, Taniere P, O’Sullivan B, Müller S, Schwaller J, Stankovic T, Knapp S. PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains. Cancer Res. 2013 Jun 1;73(11):3336-46.
Skowronska A, Parker A, Ahmed G, Oldreive C, Davis Z, Richards S, Dyer M, Matutes E, Gonzalez D, Taylor AM, Moss P, Thomas P, Oscier D, Stankovic T. Biallelic ATM inactivation significantly reduces survival in patients treated on the United Kingdom Leukemia Research Fund Chronic Lymphocytic Leukemia 4 trial. J Clin Oncol. 2012 Dec 20;30(36):4524-32.
Weston VJ, Oldreive CE, Skowronska A, Oscier DG, Pratt G, Dyer MJS, Smith G, Powell JE, Taylor AMR, Moss PAH, Stankovic T (2010). The PARP inhibitor olaparib suppresses growth of ATM mutant lymphoid tumour cells in vitro and in vivo. Blood;116(22):4578-87
Goodyear O, Agathanggelou A, Novitzky-Basso I, Siddique S, McSkeane T, Ryann G, Vyas P, Cavenagh J, Stankovic T, Moss P, Craddock C. (2010) Induction of a CTL Response to the MAGE Cancer Testis Antigen by Combined Treatment with Azacitidine and Sodium Valproate in Patients with Acute Myeloid Leukemia and Myelodysplasia. Blood;116(11):1908-18.
Bose S, Yap LF, Fung M, Starzcynski J, Saleh A, Morgan S, Dawson C, Chukwuma MB, Maina E, Buettner M, Wei W, Arrand J, Lim PVH, Young LS, Teo SH, Stankovic T, Woodman CBJ, Murray PG. (2009) The ATM tumour suppressor gene is downregulated in EBV-associated nasopharyngeal carcinoma. J Pathology (3):345-52.
Stewart GS, Panier S, Townsend K, Al-Hakim A, Kolas NK, Miller ES, Nakada S, Ylanko J, Olivarius S, Mendez M, Tagliaferro A, Pelletier L, Taubenheim N, Durandy A, Byrd PJ, Stankovic T, Taylor AMR, Durocher D. (2009) The gene mutated in the RIDDLE syndrome regulates an ubiquitin-dependent signalling cascade at sites of DNA damage. Cell; 136:420-34.
Dunwell TL, Dickinson RE, Stankovic T, Dallol A, Weston V, Austen B, Catchpoole D, Maher ER, Latif F.Frequent epigenetic inactivation of the SLIT2 gene in chronic and acute lymphocytic leukemia. Epigenetics. 2009 May;4(4):265-69.
Marston E, Weston V, Jesson J, Maina E, McConville C, Agathanggelou A, Skowronska A, Mapp K, Sameith K, Powell JE, Lawson S, Kearns P, Falciani F, Taylor M, Stankovic T. (2009) Stratification of paediatric ALL by in vitro cellular responses to DNA double strand breaks provides insight into the molecular mechanisms underlying clinical response Blood. 113(1):117-26.
Pepper C, Lin TT, Pratt G, Hewamana S, Brennan P, Hiller L, Hills R, Ward R, Starczynski J, Austen B, Hooper L, Stankovic T, Fegan C. (2008) Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers. Blood;112:3807-17Willcox-BE*, Dechanet-Merville-J*. (2012). Cytomegalovirus and tumor stress surveillance by binding of a human gamma delta T cell antigen receptor to endothelial protein C receptor. Nat Immunol 13(9): 872-9.