Multi-disciplinary, 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 dysfunction. Diseases under current investigation are: vascular complications of diabetes, renal failure and ageing ¯ particularly nephropathy and cardiovascular disease. Using systems approach to model dysfunctional lipid metabolism caused by abnormal post-translational lipoprotein modification. 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, and cancer chemoprevention and Nrf2 activators for health benefit. Mechanistic biomarker discovery: for metabolic, vascular and joint health.
I entered academic life as a mature student in 1995. After graduating in Biological and Medicinal Chemistry, I pursued pre-doctoral research improving analytical methods to identify and quantify markers of protein damage by glycation, oxidation and nitration. Damage to proteins of these types is important in mechanisms of chronic and degenerative disease mediating impairment of structural, catalytic and regulatory proteins. I gained skills and experience in mass spectrometry (LC−MS/MS stable isotopic dilution analysis of amino acids and related glycated, oxidised and nitrated derivatives, and proteomics) mammalian cell culture, pre-clinical animal pharmacology and clinical studies − working with colleagues within the host research team and with several national and international collaborating research groups. I have supervised 2 PhD students, published 54 peer-reviewed articles and 90 conference papers − h-index 22; and I have filed 3 patents. In my post-doctoral research, I continued studies developing LC-MS/MS techniques for comprehensively and quantitatively screening for protein damage in models of disease mechanisms and clinical studies and became world leaders in this field - supported by Welcome Trust. With advanced proteomics techniques, I identified proteins and sites within proteins susceptible to damage by glycation − particularly glycation by the reactive dicarbonyl methylglyoxal (MG): albumin, haemoglobin, lens crystallins and type IV collagen. Markers of damage to albumin and haemoglobin are of diagnostic relevance as markers of glycaemic control and risk of vascular disease development in diabetes. I studied markers of protein damage in clinical and experimental diabetes and diabetic complications, endstage renal disease and dialysis, cirrhosis, Alzheimer?s disease, ageing, arthritis and thermally processed foodstuffs. Damage to lens crystallins and type IV collagen is important mechanistically in the development of cataract and vascular disease, respectively. I gained national and international recognition of my work because of its original, insightful approach.
Since April 2007, I have co-directed the Protein Damage and Systems Biology Research
Group in Warwick Medical School with Professor Paul J. Thornalley. We specialise in preclinical
and clinical studies of protein damage and the anti-stress gene response in disease mechanisms, diagnostics and therapeutics − with spin-off therapeutics development (high dose thiamine therapy for diabetic vascular complications). My current research focus is investigations of damage to lipoproteins and influence of dietary bioactive compounds on lipoprotein synthesis, damage and metabolism - supported by the BHF and BBSRC. My core research project is a study of dicarbonyl glycation of apolipoprotein B100 of low density lipoprotein (LDL) and its importance in dyslipidaemia in diabetes and ageing. This includes use of mathematical models in a systems biology approach to predict consequences of change in lipoprotein function in lipoprotein metabolism following glycation. Improved understanding is also available from studies of high density lipoprotein (HDL) damage in
dyslipidaemia and atherosclerosis in diabetes and ageing. I am supervising two post−doctoral research fellows to study physiological damage and functional impairment to HDL − a BHF funded project grant.
CURRENT RESEARCH PROJECTS
BIOmarkers of Robustness of Metabolic Homeostasis for Nutrigenomics-derived Health CLAIMS Made on Food (BIOCLAIMS), with Prof Paul J Thornalley, Clinical Sciences Research Institute, Dr Naila Rabbani - Clinical Sciences Research Institute
-, Funded by: EU FP7,
Project Start Date:
01/03/2010
Project End Date:
28/02/2015
Effect of glyoxalase 1 silencing and gene deletion on development of diabetic nephropathy, Funded by: Saudi Arabian Ministry of Education,
Project Start Date:
01/01/2011
Project End Date:
30/10/2014
Anti-stress gene response in cell and tissue ageing: role of transcription factor NF-E2-related factor-2 and effect of dietary activators, Funded by: BBSRC-Unilever,
Project Start Date:
01/03/2010
Project End Date:
28/02/2014
Mechanism of increased renal clearance of thiamine in hyperglycaemia associated with diabetes., Funded by: Diabetes UK,
Project Start Date:
01/10/2008
Project End Date:
31/03/2012
Thornalley, P. J, Xue, M. and Rabbani, N.(2011) 'Methodologies for in-vitro and in-vivo activity of bioactive compounds'
in
Health-promoting properties of fruits and vegetables,
Editors:
Terry, L. (9781845935283), Oxford, UK: CABI
Kurz, A., Rabbani, N., Walter, M., Bonin, M., Thornalley, P., Auburger, G. and Gispert, S.(2011) 'Alpha-synuclein deficiency leads to increased glyoxalase I expression and glycation stress'
Cellular and Molecular Life Sciences
68
(4), 721 - 733 (1420-682X)
Kurz, A., Rabbani, N., Walter, M., Bonin, M., Thornalley, P., Auburger, G. and Gispert, S.(2011) 'Alpha-synuclein deficiency leads to increased glyoxalase I expression and glycation stress'
Cellular and Molecular Life Sciences
68
(4), 721 - 733 (1420-682X)
[article]
Thornalley, P. J. and Rabbani, N.(2011) 'Protein damage in diabetes and uremia?identifying hotspots of proteome damage where minimal modification is amplified to marked pathophysiological effect'
Free Radical Research
45
(1), 89 - 100 (1071-5762)
Rabbani, N. and Thornalley, P.J.(2011) 'Glyoxalase in diabetes, obesity and related disorders'
Seminars In Cell And Developmental Biology
In press
(1084-9521)
