Dr Chiara Bardella PhD

Dr Chiara Bardella

Institute of Cancer and Genomic Sciences
Research Fellow

Contact details

Address
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Dr Chiara Bardella was appointed as a group leader at the Institute of Cancer and Genomic Sciences in 2018. Her research is focused on understanding the mechanisms of tumour onset and progression, with a particular interest in gliomas. Gliomas account for >70% of all primary brain tumours of which glioblastomas are the most frequent and malignant. In particular, her team investigates the cellular and molecular mechanisms underlying isocitrate dehydrogenase (IDH)-driven gliomagenesis, with the aim to better understand this type of cancer and to develop effective treatments. While brain cancer is the main research topic of Bardella’s team, her interests extend to other cancer types where either IDH mutations are present, or which are driven by other important oncogenes and tumour suppressors regulating cellular metabolism (i.e. fumarate hydratase and succinate dehydrogenase).

Qualifications

  • PhD in Cellular Sciences and Technologies 2008
  • MSc in Molecular Biology 2002
  • BSc in Biological Sciences 1999

Biography

Dr Chiara Bardella started her scientific career at the Institute for Cancer Research and Treatment, Candiolo, Turin (Italy), initially as a master degree student and then a PhD student.  At that time her research experience was mostly focused on mechanisms of cellular invasion and metastasis, driven by mutated tyrosine kinase oncogenes. Throughout her PhD she had the opportunity to work extensively on cellular and mouse models of tumorigenesis, and focused her research on cancer metabolism. In particular she investigated the molecular mechanisms of tumorigenesis associated with the tumour suppressor fumarate hydratase gene (FH), achieving her PhD in Cellular Sciences and Technologies in 2008.

In 2009 she joined the Molecular and Genetic Populations Laboratory at the Wellcome Trust Centre for Human Genetics, University of Oxford, headed by Professor Ian Tomlinson. Here she had the opportunity to expand her knowledge in cancer genetics and to acquire expertise in functional studies of metabolic oncogenes and tumour suppressor genes, such as FH and IDH in different cancer contexts, such as colon, kidney and brain. During her postdoctoral experience she developed and analysed a new conditional, inducible mouse model of mutant Idh1, which represented the first mutant Idh1 mouse model to develop a phenotype clearly related to brain tumorigenesis, providing insights into how this mutant gene contributes to cancer.

Postgraduate supervision

Chiara is interested in PhD applications from talented, hard-working and enthusiastic students. If interested please send her an email .

Research

Bardella’s team research is focused on the following topics:

  •  develop and characterise mouse and cellular models of IDH1-driven tumorigenesis to identify targetable pathways
  • understanding the role of oncometabolites  in tumour onset and progression
  • identifying the cancer cell of origin (for instance in IDH-mutant tumours)
  • detecting new molecular targets and therapies
  • understanding the role of microenviroment in cancer progression

Bardella’s team employs a broad range of state-of-art techniques, from basic cellular and molecular biology to imaging, genome sequencing and editing, cutting–edge genetically engineered models and  ex vivo models.

Bardella’s group has established national and international collaborations.

Publications

Lee LY, Woolley CE, Starkey T, Biswas S, Mirshahi TS, Bardella C, Segditsas S, Irshad S, Tomlinson I. Serum- and glucocorticoid-induced kinase sgk1 directly promotes the differentiation of colorectal cancer cells and restrains metastasis. Clin Cancer Res. 2018 Oct 15. pii: clincanres.1033.2018. doi: 10.1158/1078-0432.CCR-18-1033.

Bardella C*, Al-Shammari AR*, Soares L*, Tomlinson I, O'Neill E and Szele FG (*joint first authors). The Role of Inflammation in Subventricular Zone Cancer. Prog Neurobiol. 2018 Apr 11. pii: S0301-0082(17)30198-3. doi: 10.1016/j.pneurobio.2018.04.007. Review. 

Hollinshead KER, Munford H, Eales K, Bardella C, Li C, Escribano-Gonzalez C, Thakker A,  Nonnenmacher Y, Kluckova K, Jeeves M, Murren R, Cuozzo F, Ye D, Laurenti G, Zhu W, Hiller K, Hodson DJ, Hua W, Tomlinson I, Ludwig C, Mao Y, Tennant DA. Oncogenic IDH1 mutations promote enhanced proline synthesis through PYCR1 to support the maintenance of mitochondrial redox homeostasis. Cell Rep. 2018 Mar 20;22(12):3107-3114. doi: 10.1016/j.celrep.2018.02.084. 

Irshad S, Bansal M, Guarnieri P, Davis H, Zen A, Biswas S, Pinna M, Bardella C, Jeffery R, Wang LM, East JE, Tomlinson I, Leedham SJ. Bone Morphogenetic Protein and Notch signaling crosstalk in poor prognosis, mesenchymal subtype colorectal cancer. J Pathol. 2017 Mar 15. doi: 10.1002/path.4891. 

Bardella C, Al-Dalahmah O, Krell D, Brazauskas P, Al-Qahtani K, Tomkova M, Adam J, Serres S, Lockstone H, Freeman-Mills L, Pfeffer I, Sibson N, Goldin R, Schuster-Böeckler B, Pollard PJ, Soga T, McCullagh JS, Schofield CJ, Mulholland P, Ansorge O, Kriaucionis S, Ratcliffe PJ, Szele FG and Tomlinson I. Expression of Idh1R132H in the murine subventricular zone stem cell niche recapitulates features of early gliomagenesis. Cancer Cell. 2016 Sep 21. pii: S1535-6108(16)30402-0. doi: 10.1016/j.ccell.2016.08.017; (front cover).

Kovac M*, Navas C*, Horswell S*, Salm M*, Bardella C*, Rowan A, Stares M, Castro-Giner F, Fisher R, de Bruin EC, Kovacova M, Gorman M, Makino S, Williams J, Jaeger E, Jones A, Howarth K, Larkin J, Pickering L, Gore M, Nicol DL, Hazell S, Stamp G, O'Brien T, Challacombe B, Matthews N, Phillimore B, Begum S, Rabinowitz A, Varela I, Chandra A, Horsfield C, Polson A, Tran M, Bhatt R, Terracciano L, Eppenberger-Castori S, Protheroe A, Maher E, El Bahrawy M, Fleming S, Ratcliffe P, Heinimann K, Swanton C, Tomlinson I.  (*joint first authors). Recurrent chromosomal gains and heterogeneous driver mutations characterise papillary renal cancer evolution. Nat Commun. 2015 Mar 19;6:6336. doi: 10.1038/ncomms7336. 

Krell D, Mulholland P, Stebbing J, Tomlinson I, Bardella C. HOT mutation screening in human glioblastomas. Future Sci OA. 2015;1(3). pii: FSO22. 

Davis H, Irshad S, Bansal M, Rafferty H, Boitsova T, Bardella C, Jaeger E, Lewis A, Freeman-Mills L, Giner FC, Rodenas-Cuadrado P, Mallappa S, Clark S, Thomas H, Jeffery R, Poulsom R, Rodriguez-Justo M, Novelli M, Chetty R, Silver A, Sansom OJ, Greten FR, Wang LM, East JE, Tomlinson I, Leedham SJ. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche. Nat Med. 2015 Jan;21(1):62-70. doi: 10.1038/nm.3750. 

Krell D, Mulholland P, Frampton AE, Krell J, Stebbing J, Bardella CIDH mutations in tumorigenesis and their potential role as novel therapeutic targets. Future Oncol. 2013 Dec;9(12):1923-35. doi: 10.2217/fon.13.143. Review. 

Bardella C, Olivero M, Lorenzato A, Geuna M, Adam J, O'Flaherty L, Rustin P, Tomlinson I, Pollard PJ, Di Renzo MF. Cells lacking the fumarase tumor suppressor are protected from apoptosis through a hypoxia-inducible factor-independent, AMPK-dependent mechanism. Mol Cell Biol. 2012 Aug;32(15):3081-94. doi: 10.1128/MCB.06160-11. 

Schödel J, Bardella C, Sciesielski LK, Brown JM, Pugh CW, Buckle V, Tomlinson IP, Ratcliffe PJ, Mole DR. Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression.  Nat Genet. 2012 Mar 11;44(4):420-5, S1-2. doi: 10.1038/ng.2204. 

Bardella C, Pollard PJ, Tomlinson I. SDH mutations in cancer. Biochim Biophys Acta. 2011 Nov;1807(11):1432-43. doi:10.1016/j.bbabio.2011.07.003. Review. 

Bardella C, El-Bahrawy M, Frizzell N, Adam J, Ternette N, Hatipoglu E, Howarth K, O'Flaherty L, Roberts I, Turner G, Taylor J, Giaslakiotis K, Macaulay VM, Harris AL, Chandra A, Lehtonen HJ, Launonen V, Aaltonen LA, Pugh CW, Mihai R, Trudgian D, Kessler B, Baynes JW, Ratcliffe PJ, Tomlinson IP, Pollard PJ. Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status. J Pathol. 2011 May 10. doi: 10.1002/path.2932; (front cover).

Krell D, Assoku M, Galloway M, Mulholland P, Tomlinson I, Bardella CScreen for IDH1, IDH2, IDH3, D2HGDH and L2HGDH Mutations in Glioblastoma. PLoS One. 2011;6(5):e19868. doi: 10.1371/journal.pone.0019868. 

Ashrafian H, O'Flaherty L, Adam J, Steeples V, Chung YL, East P, Vanharanta S, Lehtonen H, Nye E, Hatipoglu E, Miranda M, Howarth K, Shukla D, Troy H, Griffiths J, Spencer-Dene B, Yusuf M, Volpi E, Maxwell PH, Stamp G, Poulsom R, Pugh CW, Costa B, Bardella C, Di Renzo MF, Kotlikoff MI, Launonen V, Aaltonen L, El-Bahrawy M, Tomlinson I, Pollard PJ. Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis. Cancer Res. 2010 Nov 15;70(22):9153-65. doi: 10.1158/0008-5472.CAN-10-1949. 

Costa B, Dettori D, Lorenzato A, Bardella C, Coltella N, Martino C, Cammarata C, Carmeliet P, Olivero M, Di Renzo MF. Fumarase tumor suppressor gene and MET oncogene cooperate in upholding transformation and tumorigenesis. FASEB J. 2010 Aug;24(8):2680-8. doi: 10.1096/fj.09-146928. 

Cardamone MD, Bardella C, Gutierrez A, Croce LD, Rosenfeld MG, Di Renzo MF, De Bortoli M. ER{alpha} as ligand-independent activator of CDH-1 regulates determination and maintenance of epithelial morphology in breast cancer cells. Proc Natl Acad Sci U S A. 2009 May 5;106(18):7420-5. doi: 10.1073/pnas.0903033106. 

Bardella C, Dettori D, Olivero M, Coltella N, Mazzone M and Di Renzo MF. The therapeutic potential of Hepatocyte Growth Factor to sensitize ovarian cancer cells to cisplatin and paclitaxel  in vivo. Clin Cancer Res,13 (7): 2191-8, April 1, 2007.

Coltella N, Rasola A, Nano E, Bardella C, Fassetta M, Filigheddu N, Graziani A, Comoglio PM, Di Renzo MF. p38 MAPK turns hepatocyte growth factor to a death signal that commits ovarian cancer cells to chemotherapy-induced apoptosis. Int J Cancer, 118 (12): 2981-90, June 15, 2006. 

Bardella C, Costa B, Maggiora P, Patanè S, Olivero M, Ranzani N, De Bortoli M, Comoglio PM, Di Renzo MF. Truncated RON tyrosine kinase drives tumor cell progression and abrogates cell-cell adhesion through E-cadherin transcriptional repression. Cancer Res, 64: 5154-5161, August 1, 2004.

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