Professor Palmer earned a BSc in Genetics from Glasgow University in 1985 and a PhD in Molecular Toxicology in 1991. He worked as a American Heart Association postdoctoral fellow with Professor Eric Johnson at the Scripps Research Institute in La Jolla, California from 1991 to 1995, and joined the laboratory of Professor Roland Wolf at the Biomedical Research Centre in Ninewells Hospital in 1995. In 1998, Professor Palmer established his own laboratory at the Biomedical Research Centre, as a Principal Investigator and lecturer. His lab specializes in population genetic research and has research projects studying the genetic basis for susceptibility to common diseases such as type 2 diabetes, heart disease, asthma and cancer. This will provide new drug targets for the prevention and treatment of such diseases and will also allow for more informed and personalised usage of current therapiesHe participates as a member of the scientific committee of the Generation Scotland programme (www.generationscotland.org), and is a primary investigator of the Wellcome Trust Case Control Consortium (www.wtccc.org.uk).
- Bisgaard, H., Simpson, A., Palmer, C. N. A., et al. 2008. Gene-Environment Interaction in the Onset of Eczema in Infancy: Filaggrin Loss-of-Function Mutations Enhanced by Neonatal Cat Exposure. PLoS Med 5(6): 934-940. (12.6) .
- Freathy, R. M., Timpson, N. J., Lawlor, D. A., et al. 2008. Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected, given its effect on BMI. Diabetes 57: 1419-1426. (8.2)
- Nomura, T., Akiyama, M., Sandilands, A., Nemoto-Hasebe, I., Sakai, K., Nagasaki, A., Ota, M., Hata, H., Evans, A. T., Palmer, C. N. A., Shimizu, H., McLean, W. H. 2008. J Invest Dermatol 128: 1436-1441. (4.8)
- Zeggini, E., Scott, L. J., Saxena, R., et al. 2008. Meta-analysis of genome-wide association data and large-scale replication identifies several additional susceptibility loci for type 2 diabetes. Nat Genetics 40: 438-645. (25.5)
- McLean, W. H., Palmer, C. N. A., Henderson, J., Kabesch, M., Weidinger, S., Irvine, A. D., 2008. Filaggrin variants confer susceptibility to asthma. J Allergy Clin Immunol 121: 1294-1295. (8.1)
Lipid signalling in cancer and vascular disease
Many chemicals that are present in our diet and the environment promote the progression of diseases such as heart disease, diabetes, cancer and dementia. These chemicals mimic endogenous signalling molecules leading to inappropriate cellular responses. Our aim is to understand how chemicals, that mimic the actions of fatty acids, may modulate the progression of these diseases.
Fatty acids are detected at the cellular level by members of the steroid hormone/nuclear receptor superfamily known as peroxisome proliferator activated receptors (PPARs).
These receptors are responsible for the tight regulation of the intracellular concentrations of free fatty acids, which can be highly toxic; however it appears that PPARs also have important roles in modulating inflammation, cellular growth and differentiation.
Activation of PPARa by fatty acids and other chemicals causes liver cancer in the rats and mice. In contrast, we have shown that the human liver does not display a hyperplastic response to PPARa activators and contains very little functional PPARa. Our work suggests that PPARa activating chemicals such as the fibrate group of lipid lowering drugs do not represent a significant hepatocarcinogenic risk in man. These drugs do however impact on other cellular systems to provide protection from heart disease and, in collaboration with GlaxoSmithKline, we are currently investigating the role of PPARs in the development and prevention of atherosclerosis. We also collaborate with clinician scientists with the aim of translating this work into new treatments for cardiovascular disease. This collaboration has been formalised by the creation of the Insitiute for Cardiovascular Research and this is the subject of a major appeal.
PPARg is a crucial factor in the development of adipocytes and is the target of insulin-sensitizing drugs known as thiazolidenediones. Thiazlidenedione drugs are effective in the management of non-insulin dependent diabetes and the PPARg gene is polymorphic in populations that have a high prevalancy of non-insulin dependent diabetes. In collaboration with the Dundee Diabetes Research Centre, we are currently assessing the impact of polymorphisms in the PPAR genes on the diabetic population in Tayside.
PPARg has also been shown to be over-expressed in prostate, breast, colon and adipocytic tumours. Activation of PPARg in these cells appears to halt growth and leads to terminal differentiation. For these reasons, this receptor is a candidate target for anti-cancer drug therapy and chemoprevention. We have developed a novel screening method for the discovery of PPARg ligands and are currently screening novel compounds for their ability to bind PPARg and arrest tumour cell growth.
We are studying the interaction of non-steroidal anti-inflammatory drugs (NSAIDs) and colon cancer. NSAIDs are potent inhibitors of colon tumour growth and we are currently investigating the role of PPAR and cyclooxygenase signalling pathways in the anti-tumour action of NSAIDs. It is anticipated that this will reveal novel aspects of tumour biology that may improve cancer prevention and treatment.