Dr Karen Swales

Biography

I gained a BSc (Hons) Biochemistry (Toxicology) and a PhD in Molecular Toxicology under the supervision of  Dr Nick Plant and Prof. Gordon Gibson, from the University of Surrey, where I became interested in orphan nuclear receptors. To further this interest, I moved to North Carolina, USA to be a visiting post-doctoral fellow in the laboratory of Dr Masahiko Negishi at the National Institute of Environmental Health Sciences, researching a novel mechanism of gene regulation by the nuclear receptor CAR. I then returned to the UK, to work with Dr David Bishop-Bailey, as a post-doctoral researcher investigating the role of the nuclear receptor FXR in cardiovascular disease. I obtained a 2 year independent fellowship from Barts and the London Charitable Trust to further my research into FXR in 2007. I returned to the University of Surrey as Lecturer in Toxicology in September 2008.  

I was awarded the British Toxicology Society Early Career Investigator Prize in March 2011 for my research investigating nuclear receptors and their role in toxicity. The main receptors I currently study (PXR, FXR and CAR) make up a network that  in response to potentially toxic compounds, including drugs and bile acids, regulate gene expression and thus protect the body from toxicity. I am now investigating whether this network can also protect against common diseases in humans, such as cardiovascular disease and cancer.  

Research Interests

My current research focuses on the nuclear receptors, pregnane X receptor (PXR), farnesoid X receptor (FXR) and constitutive androstane receptor (CAR). These receptors make up a network that in response to chemical insults, such as drugs and bile acids, regulate gene expression and thus protect the body from toxicity. Given the impact of lifestyle and environment on key human diseases, such as breast cancer and cardiovascular disease, my work at Surrey is focussed on determining whether the changes in gene regulation mediated by the aforementioned nuclear receptors can be harnessed to protect against the development of these diseases.

Breast Cancer:

Breast cancer accounts for around 17% of female deaths from cancer in the UK, it is essential that new therapies are developed, diagnostic markers identified and the disease process understood. One potential novel therapeutic target is the nuclear receptor FXR. FXR is activated by bile acids, which have been shown to be present in some breast cancers and in breast cyst fluid. I have shown that FXR is expressed in human breast cancer, as well as being present and pro-apoptotic in human breast cancer cell lines. I also found that FXR  down-regulates the enzyme aromatase, responsible for local pro-proliferative estrogen production, in human breast cancer cell lines. As breast cancer prognosis is dependent, not only, on the growth of the tumour but on its aggressiveness and metastasis to other organs, I am now investigating FXR as a novel therapeutic target for later stage breast cancer.  

Cardiovascular Disease:
The vasculature is exposed to circulating endogenous, dietary and foreign chemicals. These chemical insults can contribute to the development of endothelial dysfunction, the initiating event in atherosclerosis. My previous work showed in vascular smooth muscle cells that FXR is anti-inflammatory and anti-migratory and therefore potentially anti-atherosclerotic. I have now shown that PXR can sense chemical insults and up-regulates drug metabolism and transport to protect against toxicity in the vasculature similar to its role in the liver and that it additionally protects against vascular oxidative stress. 

Research Collaborations

Dr Masahiko Negishi 

National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina, USA

Dr David Bishop-Bailey

Professor Timothy Warner

Dr Sanjeev Kumar

Professor Magdi Yaqoob

William Harvey Research Institute, Barts and the London - Queen Mary's School of Medicine and Dentistry, London

Dr Helen Coley

Dr Nick Plant

University of Surrey

Publications

See my new Cardiovascular Research publication here on PXR- novel protective gatekeeper of the vasculature

Teaching

Undergraduate

BMS1030     Biochemistry 1

BMS2036     Molecular Biology and Genetics 2 (Module organiser)

BMS3010     Mechanisms of Toxicity

Postgraduate

MSc (Toxicology)

TOXM001     Principles of Toxicology 1 

TOXM002     Principles of Toxicology 2

TOXM003     Tissue Specific Toxicity 1 (Module Organiser)

TOXM004     Tissue Specific Toxicity 2

TOXM007     Techniques in Toxicology

MSc (Drug Discovery and Design)

CHEM017     Pharmacology and Toxicology

MSc (Applied Toxicology)

Target Organ Toxicology – Systems I: Liver, Kidney, GI Tract and Skin

Departmental Duties

FHMS Research Events Co-ordinator

    Follow links for information on events within FHMS or the annual Festival of Research 

Faculty Research and Enterprise Committee (FRC)

Chair of the FRC Faculty Research Support Fund (FRSF) Sub-committee

Module Organiser - TOXM003 Tissue Specific Toxicity 1 

                                BMS2036 Molecular Biology and Genetics 2