We focus on the discovery of new knowledge of the mechanisms that underlie tumour development and application of this knowledge to improve prevention, diagnosis and treatment of cancer.
Our goal is to identify the genetic causes of tumour development and translate that research into medical practice.
- Dr Ming Shen, Package Lead
- Dr Jian Yang
What we do
We provide new knowledge of the molecular genetic mechanisms underlying tumorigenesis, using genetic strategies to elucidate the mechanisms through which inherited and somatic genetic variants lead to tumour development.
We identify the genes and epigenetic changes involved in these diseases, establish their functions and develop DNA diagnostics and undertake pre-clinical and clinical trials of new targeted therapies.
We investigate genes and pathways in cancers including those that affect the kidneys and bowel. Our research includes in vitro studies with cultures cells, in vivo pre-clinical investigations using animal cancer models and clinical trials in patients with inherited tumour syndromes. We examine tumour samples and normal counterparts from patients to determine molecular mechanisms of tumourigenesis and treatment response. We focus on the mTOR pathway that is involved in many cancers such as renal carcinoma. We dissect this oncogenic pathway by conditional knockout of genes in mTOR associated tumours or pharmacological inhibition of mTOR signalling in model systems. We screen for and test inhibitors of mTOR and other related oncogenic signalling pathways for prevention and therapy of cancer in model systems that can be translated into clinical practice.
Genetic tests for cancer predisposing genes have been transferred to the NHS, and commercialised in North America. Our pre-clinical research and clinical trials paved the way for approval of drugs called mTOR inhibitors for kidney and brain tumours in patients with the genetic disorder Tuberous Sclerosis.
Kalin Narov, Jian Yang, Paulina Samsel, Ashley Jones, Julian R. Sampson and Ming Hong Shen (2017)The dual PI3K/mTOR inhibitor GSK2126458 is effective for treating solid renal tumours in Tsc2+/- mice through suppression of cell proliferation and induction of apoptosis. Oncotarget 2017 Apr 19. doi: 10.18632/oncotarget.17215. [Epub ahead of print]
Jian Yang, Paulina A. Samsel, Kalin Narov, Ashley Jones, Daniel Gallacher, John Gallacher, Julian R. Sampson and Ming Hong Shen (2017)Combination of Everolimus with Sorafenib for Solid Renal Tumors in Tsc2+/- Mice Is Superior to Everolimus Alone. Neoplasia. 2017 Feb;19(2):112-120. doi: 10.1016/j.neo.2016.12.008.
Jian Yang, Maria Kalogerou, Paulina A. Samsel, Yadan Zhang, David F. R. Griffiths, John Gallacher, Julian R. Sampson and Ming Hong Shen(2015)
- Kayleigh M. Dodd, Jian Yang, Ming Hong Shen, Julian Sampson and Andrew R. Tee (2015) mTORC1 drives HIF-1α and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3. Oncogene 34, 2239–2250
- Jian Yang, Maria Kalogerou, John Gallacher , Julian R. Sampson and Ming Hong Shen (2013)
Renal tumours in a Tsc1+/– mouse model show epigenetic suppression of organic cation transporters Slc22a1, Slc22a2 and Slc22a3, and do not respond to metformin. European Journal of Cancer 49:1479-1490
- Maria Kalogerou, Yadan Zhang, Jian Yang, Nigel Garrahan, Stephen Paisey, Paweł Tokarczuk, Andrew Stewart, John Gallacher, Julian R. Sampson and Ming Hong Shen (2012) T2 weighted MRI for assessing renal lesions in transgenic mouse models of tuberous sclerosis European Journal of Radiology 81: 2069–2074
Cardiff University have invested approximately £5M in a state-of-the-art research building dedicated to Cancer Genetics on the Heath Park campus. The building was completed early in 2010 and provides superb facilities for much of the cancer-related work of the Wales Gene Park.
For further details contact the Package Lead, Dr Ming Shen at ShenMH@Cardiff.ac.uk.