Dr. Tatyana Chernova
Senior Investigator Scientist
MRC Toxicology Unit
LE1 9HN, UK
Tel: +44 116 2525618
Dissecting the molecular changes during the progression of malignant mesothelioma with the overall aim of improving therapeutic strategies
Malignant mesothelioma (MM) is a highly aggressive tumour with a dismal prognosis. MM is a unique cancer strongly related to former asbestos exposure The incidence of MM in the UK has increased more than 10-fold in the last 40 years and due to reach its peak in around 2020.
There are substantial gaps in our understanding of the fundamental mechanisms of MM development, and to date most clinical trials have focused on the use of cytotoxic agents rather than targeted therapies.
MM research will use an unbiased system biology based approach and carry out transcriptional profiling, micro-RNA profiling, and translational profiling to identify pathways involved in the development of the disease. This study will develop in the following directions:
(i)Examining mechanisms involved in malignancy and identifying potential drivers for carcinogenesis using primary tissues/effusions. The data obtained at this stage will inform our future work and should provide new markers for early/better diagnosis of MM and potentially contribute to a more personalized approach in treatment.
(ii) Using mesothelioma as a model for other cancers. We will explore the relevance of molecular changes identified in MM to more general mechanisms of malignancy.
(iii) Implications of our findings for exposure to alternative fibres and nanoparticles. It is possible that these newer fibres may also contribute to the development of diseases of the respiratory system by triggering similar responses to asbestos. Thus, information gained from this study could also provide valuable insight into other diseases that could result from exposure to exogenous particles including carbon fibre nanoparticles.
Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease.
Chernova T, Sun XM, Powley IR, Galavotti S, Grosso S, Murphy FA, Miles GJ, Cresswell L, Antonov AV, Bennett J, Nakas A, Dinsdale D, Cain K, Bushell M, Willis AE, MacFarlane M.
Cell Death Differ. 2016 Jul;23(7):1152-64. doi: 10.1038/cdd.2015.165.
Pulmonary toxicity of carbon nanotubes and asbestos – similarities and differences.
Donaldson K, Poland CA, Murphy FA, MacFarlane M, Chernova T, Schinwald A.
Adv Drug Deliv Rev. 2013 Dec;65(15):2078-86. doi: 10.1016/j.addr.2013.07.014.
Early failure of N-methyl-D-aspartate receptors and deficient spine formation induced by reduction of regulatory heme in neurons.
Chernova T, Steinert JR, Richards P, Mistry R, Challiss RA, Jukes-Jones R, Cain K, Smith AG, Forsythe ID.
Mol Pharmacol. 2011 May;79(5):844-54. doi: 10.1124/mol.110.069831
Nitric oxide signaling in brain function, dysfunction, and dementia.
Steinert JR, Chernova T, Forsythe ID.
Neuroscientist. 2010 Aug;16(4):435-52. doi: 10.1177/1073858410366481