Basic Research > Maintenance of Genome Stability > Dr Mark Boyd

Our research group includes Carlos Rubbi and Nikolina Vlatkovic and we are funded by Cancer Research UK, the MRC and Mersey Kidney Research to investigate several aspects of the process of cancer development and progression including mechanisms regulating genomic stability. We have excellent local collaborations with the Clatterbridge Research Group (Sibson), the Biomarkers group (Liloglou), the Head and Neck Cancer clinical research teams led by Jones and Shaw). We are also collaborating externally with a number of groups and have relatively new ones with scientists at the Paterson Institute (Malliri), in Oxford (Kelsh), the Karolinska (Selivanova) and in Hannover (Kotlyarov) and with SibTech Inc. in the USA. We have projects focussing on disease progression in renal cancer (clear cell renal carcinoma) and are also investigating the functional consequences of molecular alterations in squamous cell carcinomas of the head and neck.

As part of our investigation of p53-mediated responses the group is investigating the cellular response (cell cycle arrest, DNA repair, apoptosis, senescence) to genotoxic stresses with a particular focus on the p53/MDM2 axis. Biochemically these cellular responses are regulated by a range of post-translational modifications and these are themselves under the control of higher order regulation through sub-cellular compartmentalisation. A novel MDM2 binding protein (MTBP) that inhibits MDM2 ubiquitination was identified by us and we have also discovered that p53 activation can be controlled by the nucleolus (Rubbi). Recent work has identified a p53-independent activity of MDM2 that modulates sensitivity to chemotherapeutic drugs and has consequences for cellular one-carbon metabolism, with implications for global control of methylation. We are interested in how cells prioritise one stress response over another and this question is being approached at three levels: at the cellular level by studying subcellular compartmentalisation of response pathways; at the histological level by studying changes in cell motility/invasiveness and at the genetic level by translating our biochemical findings into transgenic models. This understanding of the cellular responses to genotoxic stresses is being applied to the identification of new and better targets for therapy. For example, our studies suggest that organelle function (ribosomal biogenesis/nucleolar transport) can translate genotoxic stress into p53 activation, therefore defining a host of new potential targets for therapeutic intervention. Taking advantage of the clinical expertise and resources this basic research is being translated in to clinically relevant settings particularly in renal cancer and in head and neck cancer.

Education and qualifications

Appointments



Honours and awards

Boyd, M.T. and Vlatkovic, N. (2008). p53: a molecular marker for the detection of cancer. Expert Opinion on Medical Diagnostics 2; 1013-1024.

Maguire, M., Nield, P.C., Devling, T., Jenkins, R.E., Park, B.K., Polanski, R., Vlatkovic, N., and Boyd, M.T. (2008). MDM2 regulates DHFR activity through mono-ubiquitination. Cancer Research 68; 3232-3242.

Boyd, M.T., and Vlatkovic, N. (2008). MDM2 polymorphisms and cancer risk in basal cell carcinoma. British Journal of Dermatology 158; 636-636.

Vlatkovic, N. and Boyd, M.T. (2006). Models of cancer. Drug Discovery Today: Disease Models 3; 127-128.

Warburton, H.E., Brady, M., Vlatkovic, N., Linehan, W.M., Parsons, K., and Boyd, M.T. (2005). p53 regulation and function in renal cell carcinoma. Cancer Research 65; 6498-6503.

Brady, M., Vlatkovic, N., and Boyd, M.T. (2005). Regulation of p53 and MDM2 activity by MTBP. Mol. Cell. Biol. 25; 545-553.

Jones, L.E., Humphreys, M.J., Campbell, F., Neoptolemos, J.P., and Boyd, M.T. (2004). Comprehensive Analysis of Matrix Metalloproteinase and Tissue Inhibitor expression in Pancreatic cancer: Increased expression of MMP-7 predicts poor survival. Clin. Cancer Res. 10; 2832-2845.

Asahara, H.,  Li, Y., Fuss, J., Haines, D.S., Vlatkovic, N., Boyd, M.T. and Linn, S. (2003). Stimulation of Human DNA Polymerase  e  by MDM2. Nucleic Acids Res.31; 2451-2459.

Brady, M., Bhatia, M., Christmas, S., Boyd, M.T., Neoptolemos, J.P., and Slavin, J. (2002) Expression of the chemokines MCP-1/JE and CINC in early acute pancreatitis. Pancreas 25; 260-269.

Boyd, M.T., Vlatkovic, N., and Haines D.S. (2000). A novel cellular protein MTBP binds to MDM2 and induces a G1 arrest that is suppressed by MDM2. J. Biol. Chem.275; 31883-31890.

Vlatkovic, N., Guerrera, S., Y., Li, S., Linn, D.S., Haines, and Boyd, M.T. (2000). MDM2 interacts with the carboxy terminus of the catalytic subunit of DNA polymerase Epsilon. Nucleic Acids Res. 18; 3581-3586.

Boyd, M.T., D.B. Zimonjic, D.B., Popescu, N.C., Athwal, R., and Haines, D.S. (2000). Assignment of the MDM2 binding protein (MTBP) gene to human chromosome band 8q24 by in situ hybridization Cytogenetics and Cell Genetics. 90; 64-65.

Boyd, M.T. and Vlatkovic, N. (2008). p53: a molecular marker for the detection of cancer. Expert Opinion on Medical Diagnostics 2; 1013-1024.

Maguire, M., Nield, P.C., Devling, T., Jenkins, R.E., Park, B.K., Polanski, R., Vlatkovic, N., and Boyd, M.T. (2008). MDM2 regulates DHFR activity through mono-ubiquitination. Cancer Research 68; 3232-3242.

Boyd, M.T., and Vlatkovic, N. (2008). MDM2 polymorphisms and cancer risk in basal cell carcinoma. British Journal of Dermatology 158; 636-636.

Vlatkovic, N. and Boyd, M.T. (2006). Models of cancer. Drug Discovery Today: Disease Models 3; 127-128.

Warburton, H.E., Brady, M., Vlatkovic, N., Linehan, W.M., Parsons, K., and Boyd, M.T. (2005). p53 regulation and function in renal cell carcinoma. Cancer Research 65; 6498-6503.

Brady, M., Vlatkovic, N., and Boyd, M.T. (2005). Regulation of p53 and MDM2 activity by MTBP. Mol. Cell. Biol. 25; 545-553.

Jones, L.E., Humphreys, M.J., Campbell, F., Neoptolemos, J.P., and Boyd, M.T. (2004). Comprehensive Analysis of Matrix Metalloproteinase and Tissue Inhibitor expression in Pancreatic cancer: Increased expression of MMP-7 predicts poor survival. Clin. Cancer Res. 10; 2832-2845.

Asahara, H.,  Li, Y., Fuss, J., Haines, D.S., Vlatkovic, N., Boyd, M.T. and Linn, S. (2003). Stimulation of Human DNA Polymerase  e  by MDM2. Nucleic Acids Res.31; 2451-2459.

Brady, M., Bhatia, M., Christmas, S., Boyd, M.T., Neoptolemos, J.P., and Slavin, J. (2002) Expression of the chemokines MCP-1/JE and CINC in early acute pancreatitis. Pancreas 25; 260-269.

Boyd, M.T., Vlatkovic, N., and Haines D.S. (2000). A novel cellular protein MTBP binds to MDM2 and induces a G1 arrest that is suppressed by MDM2. J. Biol. Chem.275; 31883-31890.

Vlatkovic, N., Guerrera, S., Y., Li, S., Linn, D.S., Haines, and Boyd, M.T. (2000). MDM2 interacts with the carboxy terminus of the catalytic subunit of DNA polymerase Epsilon. Nucleic Acids Res. 18; 3581-3586.

Boyd, M.T., D.B. Zimonjic, D.B., Popescu, N.C., Athwal, R., and Haines, D.S. (2000). Assignment of the MDM2 binding protein (MTBP) gene to human chromosome band 8q24 by in situ hybridization Cytogenetics and Cell Genetics. 90; 64-65.

	Biography	Role	Email	Telephone	Location
	Dr Mark Boyd	Reader & Director of Laboratories, Head of the p53/MDM2 Research Group		+44(0)151 706 4185	5th floor, Duncan Building