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Protein Damage and Systems Biology Group

 Prof Paul Thornalley  naila_photo.jpg

Professor Paul J Thornalley

Professor of Metabolic Biochemistry & Systems Biology

Dr Naila Rabbani

Associate Professor of Experimental Systems Biology


Prof Paul J Thornalley and Dr Naila Rabbani co-direct the Protein Damage and Systems Biology Group in the Clinical Sciences Research Institute.

They lead a team of:

  • 4 post-doctoral researchers

  • 6 PhD students

  • 1 technician

In investigations of protein damage and anti-stress genes responses that protect against it in studies of vascular complications of diabetes, obesity, renal failure, neurological disorders and ageing. The team collaborates with other research teams in Systems Biology Centre and Departments of Chemistry, Biological Sciences, Statistics and Engineering in the University and clinical investigators in the University Hospital of Coventry and Warwickshire

The team is linked to Warwickshire Institute for Diabetes, Endocrinology & Metabolism (WISDEM), Warwick Centre for Analytical Sciences and clinical teams at the University Hospital of Coventry & Warwickshire (UHCW) and elsewhere. Many external collaborations with research teams in universities and companies nationally and internationally are also on-going.


Paul Thornalley - Professor of Protein Damage and Systems Biology
Clinical Sciences Research Institute
University of Warwick, University Hospital
Clifford Bridge Road
Coventry
CV2 2DX
 
T: +44 (0)24 7696 8594
M: +44 (0)7884 331407
F: +44 (0)24 7696 8653
 
Naila Rabbani - Associate Professor of Experimental Systems Biology
Clinical Sciences Research Institute
University of Warwick, University Hospital,
Clifford Bridge Road
Coventry
CV2 2DX
 
T: +44 24 7696 8593
F: +44 24 7696 8653

 

Academic PA

T: +44 (0)24 7696 8592

Research profile

Protein Damage and Systems Biology are a multi-disciplinary group, working in the field of disease mechanisms - particularly in the study of damage to the proteome by glycation, oxidation and nitration, related enzymatic countermeasures and other metabolic dysfunctions.

Diseases under current investigation are:

  • Vascular complications of diabetes
  • Renal failure
  • Ageing

Therapeutic problems under current investigation are:

  • High dose thiamine therapy for the prevention of diabetic nephropathy
  • Dialysis renal replacement therapy
  • Multi-drug resistance in cancer chemotherapy

Research interests are covered in more detail in the Research Interests section.


Funding

The group receives funding from the BBSRC, Wellcome Trust, British Heart Foundation, Diabetes UK, European Union, British Council (Prime Minister's Initiative-2) and other sources.

Major areas of research interest
  • Dysfunctional Lipoprotein Metabolism in Obesity and Diabetes - Studies of hotspot sites of lipoprotein damage in vivo, change in lipoprotein functionality, risk of atherosclerosis and lipoprotein systems modelling in diabetes.
  • Thiamine Metabolism & Therapy in Diabetes - Disturbance of thiamine metabolism in diabetes and high dose thiamine supplementation for the prevention of vascular disease in diabetes. Systems modelling of the disturbance in thiamine metabolism in diabetes and obesity.
  • Anti-Stress Gene Responses - Studies of genomic and pharmacological regulation of gene expression via transcription factor NRF2 protective against chronic disease development and ageing. Systems modelling of the NRF2 - Anti-Stress gene response.
  • Multidrug Resistance in Cancer Chemotherapy - Overexpression of glyoxalase I in innate and acquired multidrug resistance in cancer chemotherapy. Metabolomics and signalling in response to DNA damage
  • Biomedical Proteomics: Protein Damage and Proteolytic Debris - Studies of protein damage in mechanisms of chronic disease particularly vascular complications of diabetes, obesity, renal failure, neurological disorders and ageing. Quantitation of protein damage by mass spectrometry (stable isotopic dilution analysis and quantitative proteomics). Bioinformatics prediction of sites of protein damage. Systems modelling of physiological kinetics of protein damage and repair, replacement and proteolysis of damaged proteins

Current research projects

Protein damage research
  • Analysis of protein damage by glycation, oxidation and nitration in diet, plasma and urine
  • BIOmarkers of Robustness of Metabolic Homeostasis for Nutrigenomics-derived Health BIOCLAIMS Made on Food (BIOCLAIMS) -EU FP7 research network
  • Hotspot glycation of apolipoprotein B100 in LDL - importance in dyslipidaemia and atherosclerosis in diabetes and ageing
  • Hotspot glycation of apolipoprotein A-1in HDL - importance in dyslipidaemia and atherosclerosis in diabetes and ageing
Anti-stress gene response research
  • Dietary activators of antioxidant response element-linked gene expression for good vascular health
  • Anti-stress gene response in cell and tissue ageing: role of transcription factor NF-E2-related factor-2 and effect on dietary activators
>Thiamine research
  • High dose thiamine therapy for regression of microalbuminuria in patients with type 2 diabetes
  • Mechanism of increased renal clearance of thiamine in hyperglycaemia associated with diabetes and link to risk of vascular complications of diabetes
  • Epidemiological cross-sectional study on B-vitamin acid status in South-East Asian diabetic patients
  • Role of circulating advanced glycation end products (AGEs) in diabetic nephropathy: Effect of Benfotiamine intervention

Research Team

  • Dr Mingzhan Xue - Cellular and moecular Biology of glyoxalase -1
Japan Society for the Promotion of Science Fellow
  • Dr Makoto Arai - Molecular mechanisms of glycation and oxidative stress in psychiatric disorders
Post-doctoral Research Fellows
  • Dr Jinit Masania - BIOmarkers of Robustness of Metabolic Homeostasis for Nutrigenomics-derived Health CLAIMS Made on food (BIOCLAIMS)
  • Dr Fozia Shaheen - Quantiitation of methyloglyoxal and related dicarbonyls

PhD Students

  • Mr Usman Ahmed - Protein damage markers in diagnosis, progression and treatment of arthritis
  • Miss Amy Tym - Glycation and beta-cell dysfunction>
  • Dr Zehra Irshad - Dicarbonyl glycation and metabolic dysfunction in human endothelial cells in hyperglycaemia in vitro
  • Miss Florence Hariton - Anti-stress gene response in cell and tissue ageing: role of transcription factor NF-E2-related factor-2 and effect of dietary activators.
  • Mr Alaa Shafie - Influence of glyoxalase 1 on the development of diabetic nephropathy.
  • Mrss Andrea Lopez-Clavijo. Binding site identification of glyoxal in Substance P by mass spectrometry.
  • Mrs Amal Ashour - Dicarbonyl stress in periodontal disease.
Technician:

Dr Attia Anwar - Mass spectrometry and proteomics