Medicine

Why does Glucophage (metformin) help some people with diabetes?

Much current research is focused on insulin resistance and how it might be reversed where current treatments are ineffective. The best treatment for insulin-resistant T2D is metformin but the target of this drug is still unclear, hampering development of improved agents to replace metformin, which is not effective in all T2DM and loses potency with prolonged use.

How do cells decide which pathway to use to repair DNA Breaks and what is the impact on cancer?

The DNA Damage Response (DDR) is a major component of a cells defence against disease. It serves to recognize and repair DNA damage, to regulate cell-cycle progression and where necessary, promote programmed cell death. One of the most potentially dangerous forms of DNA damage is a double stranded DNA break (DSB), which must be dealt with to maintain the structural and genetic integrity of a cell. Failure to do so results in generation of chromosomal aberrations such as chromosomal translocations that are potentially tumorigenic.

Investigation of the molecular mechanism of metformin

Much current research is focused on insulin resistance and how it might be reversed where current treatments are ineffective. The best treatment for insulin-resistant Type 2 diabetes (T2D) is metformin but the target of this drug is still unclear, hampering development of improved agents to support metformin, which is not effective in all T2D and loses potency with prolonged use.

Chronic Heart failure [CHF] and the study of pharmacogenomics: Towards customized medicine in CHF therapy

There is increasing evidence that genetic variability can play an important role in inter individual response to medication. Variants of genes have been reported to modulate the response to drugs that are used in heart failure such as beta-blockers and diuretics. However their impact on outcome is yet to be established and it is likely that many other as yet undiscovered variants are likely to also have a significant impact.

The genomics of cardiovascular disease and drug response in type 2 diabetes

The field of personalised medicine is being transformed by the use of whole genome technology.  We are currently studying a population of 9000 individuals with type 2 diabetes to determine the genetic factors in determining their response to a wide range of commonly used drugs such as the statin family of cholesterol lowering drugs and anti-clotting agents such as aspirin.  The use of these drugs may be limited by side effects such as muscle pain, in the case of statins, and stomach bleeding in the case of aspirin.   We have performed a whole genome scan in 8000 individuals with type 2 diab

Linking Genomics to Imaging data: Elucidation of the mechanisms of novel genes that predispose to heart disease

Genome wide studies have provided great insight into the truly polygenic nature of cardiovascular disease, with current meta-analysis being performed in populations of ~200,000 study individuals.  This has characterised around 60 loci involved in susceptibility to CAD.  This analysis combines a wide range of cardiovascular phenotypes including angina, IMT, atheroplasty and MI. So the role of these genes in individual components of cardiovascular disease such as atherosclerosis, vessel damage, heart muscle physiology etc. has not yet been elucidated.

Control of the cell response to chemotherapy by modulating degradation of p53 protein isoforms

We demonstrated that the p53 tumour suppressor gene expresses at least twelve different p53 proteins due to alternative splicing, alternative initiation of translation and alternative promoter usage. We determined that p53 isoform proteins are expressed in normal human tissue in a tissue dependent manner. P53 isoforms are abnormally expressed in a wide range of cancer and are associated with breast cancer prognosis.

What regulates the alternative splicing of the TP53 gene and how can we take control of it to change cell fate outcome in response to cellular stress?

We demonstrated that the p53 tumour suppressor gene expresses at least twelve different p53 proteins due to alternative splicing, alternative initiation of translation and alternative promoter usage. We determined that p53 isoform proteins are expressed in normal human tissue in a tissue dependent manner. P53 isoforms are abnormally expressed in a wide range of cancer and are associated with breast cancer prognosis.

Leptin: a novel therapeutic target in Alzheimer’s disease?

Alzheimer’s disease (AD) is a progressive brain disorder that leads to profound cognitive and memory impairments. The prevalence of AD is predicted to rise rapidly in the future, which will pose a huge burden on health care services in the coming years. Evidence is growing that diet and lifestyle are key risk factors for developing AD and clinical studies indicate that metabolic dysfunction is a common trait in AD.

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