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Dr Luigi Gnudi MD PhD FRCP FASN

Professor of Diabetes and Metabolic Medicine
Honorary Consultant in Diabetes and Endocrinology
Head, Unit for Metabolic Medicine, Cardiovascular Division

Gnudi,LuigiKing's College London, 3rd Floor
Franklin-Wilkins Building
Waterloo Campus, Stamford Street
London SE1 9NH
Phone: +44 (0) 207 848 4413
Fax: +44 (0) 207 848 4567
Email: luigi.gnudi@kcl.ac.uk

Biography

Luigi Gnudi obtained his MD with Honours from the University of Parma (Italy) in 1988. He subsequently joined the residency programme at the School of Diabetes and Endocrinology at the University of Padua-Italy (1989-1993). During 1993-1995, he worked as a postdoctoral fellow with Prof Barbara B Kahn at Beth Israel Hospital, Harvard Medical School in Boston. In 1998 he obtained a PhD in Endocrinological Sciences from the University of Milan. He became a Fellow of both the Royal College of Physicians and the American Society of Nephrology in 2005. Dr Gnudi joined the Unit for Metabolic Medicine (within the Department of Diabetes, Endocrinology and Internal Medicine) in 1997 as Senior Lecturer and was promoted to Professor of Diabetes and Metabolic Medicine in 2011. He became Head of the Unit for Metabolic Medicine in 2010. Prof Gnudi is an Honorary Consultant Physician in Diabetes, Endocrinology and Metabolic Medicine at Guy's and St Thomas' Hospital NHS Foundation Trust.

Prof Gnudi is subject editor for Nephrology dialysis and Transplantation, Metabolism, and Journal of the American Society of Hypertension and past President of the Italian Medical Society of Great Britain. Prof Gnudi is a member of Diabetes UK, European Association for the Study of Diabetes, American Diabetes Association, American Society of Nephrology, European Diabetic Nephropathy Study Group, Physiological Society, ERA-EDTA, and also Faculty 1000.

Research interests

Historically, the Unit’s research has been concerned with microvascular complications in diabetes with a special interest in the kidney. The Unit has been instrumental in discovering early markers of renal disease in diabetes (most importantly microalbuminuria, Prof Viberti), looking at their prognostic value and examining treatment options for prevention of renal failure. The results of this research have been translated into everyday clinical practice and have expanded from diabetes to essential hypertension, ischaemic heart disease, and heart failure.

Under Prof Gnudi, this clinical translational work continues in the Unit. As a Member of the NIHR Biomedical Research Centre’s Faculty of Translational Medicine, Prof Gnudi is actively involved as lead PI in conjunction with the Joint Clinical Trials Office in a number of clinical trials looking new treatment for the metabolic control of diabetes and chronic vascular complication.

The Unit’s basic research activities in to the mechanisms of diabetic vascular complications have previously demonstrated:
• Glucose transporter-1 as a novel link between the haemodynamic and metabolic perturbations that contribute to progressive glomerular injury in conditions. characterised by glomerular hypertension.
• The role of the hexosamine pathway on TGFβ1 expression and the role of protein kinase-C and p38-MAPK in extracellular matrix production and fibrosis in the mesangium.
• The role of IGF-I as an inducer of VEGF mRNA expression and protein secretion in human mesangial cells via a Src-dependent mechanism.
• The determinants of arterial stiffness in patients with Type 2 diabetes and the blood pressure independent effect of angiotensin type 1 receptor blockade on improving arterial stiffness.
• The role of diuretics in the management of PPARγ induced fluid retention.
• The role of angiopoietins and VEGF-A in glomerular albumin permeability.

Prof Gnudi’s current work is mainly concerned with the study of the mechanisms regulating vascular permeability and vascular integrity in the kidney with the object of preventing end stage renal failure. The current research programme of the Unit covers the mechanisms of glomerular injury initiated by metabolic, haemodynamic, immunological, and oxidative insults. Loss of glomerular vascular permselectivity, marked by leakage of protein into the urinary space, is a key first step in many clinical conditions which induce vessel wall injury. Proteinuria is a recognised marker of renal disease and represents generalised vascular damage. Our programme utilises in vitro (cell culture), ex vivo (kidney biopsies, peripheral circulating progenitor endothelial cells), and in vivo (animal model of proteinuria, transgenics) research approaches, and provides an ideal setting for integrated research. The Unit is funded by government agencies (BBSRC, MRC), charities (Diabetes UK, NKRF, EFSD), and industry.

Main research programme

• Studies in renal mesangial and epithelial cells exploring the intracellular molecular mechanisms mediating the effect of haemodynamic/ metabolic perturbations on various cellular pathways involved in the pathogenesis of diabetic glomerulopathy (Maltese, Gnudi).

• Role of antioxidant gene expression and oxidative stress on mechanical stretch-mediated extracellular matrix production in human mesangial cells (Gnudi, Siow, Mann).

• Isolation and characterisation of circulating progenitor endothelial cells obtained from Type 1 diabetic patients with and without kidney disease (Gnudi).

• Generation of transgenic mice to modulate, with an inducible cell-specific system in renal glomeruli, the expression of vascular growth factors (Gnudi).

• Study of proteinuria and arterial stiffness in type 1/ 2 diabetes and the methods of reversing these abnormalities (Karalliedde, Viberti, Gnudi).

• Epidemiological study to identify the prevalence and determinants of type-2 diabetes, impaired glucose tolerance and cardiovascular disease in a young urban population. (Karalliedde, Viberti, Gnudi, with Dr Wijesuriya, WHO Sri Lanka, Diabetes Association of Sri Lanka, International Diabetes Federation).

• Role of active vitamin D on arterial stiffness, left ventricular hypertrophy, and albuminuria (Karalliedde, Gnudi).

• A number of ongoing clinical trials and clinical physiology studies related to the effects of anti-hypertensive and/or anti-diabetic drugs on kidney related physiological/ pathophysiological parameters (Karalliedde, Maltese, Gnudi).

Gnudi,LuigiImage425w

Group members

Professors

  • Professor G Viberti (Emeritus Professor - Clin)
  • Professor H Keen (Emeritus Professor - Clin)

Lecturers

  • Dr J Karalliedde (part-time PhD student - Clin)
  • Dr G Maltese (Locum - Clin)

Postdoctoral Fellows

  • Dr C Dessapt-Baradez

Research Assistants

  • Miss A Hayward

Research Nurses

  • Ms B Clarkson-Dodd
  • Ms S Gillman

Selected publications

• Wijesuriya M, Gulliford M, Charlton J, Vasantharaja L, Viberti GC, Gnudi L, Karalliedde J. High Prevalence of Cardio-Metabolic Risk Factors in a Young Urban Sri-Lankan Population. PLoS One, 7(2), e31309, 2012.

• Shahni R, Gnudi L, King A, Jones P, Malik AN. Elevated levels of renal and circulating Nop-7-associated 2 (NSA2) in rat and mouse models of diabetes, in mesangial cells in vitro and in patients with diabetic nephropathy. Diabetologia, 55(3):825-34, 2012.

• Dessapt-Baradez C, Reza M, Sivakumar G, Hernandez-Fuentes M, Markakis K, Gnudi L, Karalliedde J. Circulating vascular progenitor cells and central arterial stiffness in polycystic ovary syndrome. PLoS One, 6(5):e20317, 2011.

• Karalliedde J, Gnudi L. Endothelial factors and diabetic nephropathy. Diabetes Care, 34 (2):S291-6, 2011.

• Setti G, Hayward A, Dessapt C, Barone F, Buckingham R, White K, Bilous R, Hiroshi K, Gruden G, Viberti GC, Gnudi L. PPAR-γ Agonist Rosiglitazone Prevents Albuminuria but not Glomerulosclerosis in Experimental Diabetes. Am J Nephrol, 3;32(5):393-402, 2010.

• Rosenstock J, Lorber DL, Gnudi L, Howard CP, Bilheimer DW, Chang PC, Petrucci RE, Boss AH, Richardson PC. Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomised trial. The Lancet, 375:2244-2253, 2010.

• Dei Cas A, Spigoni V, Ardigò D, Pedrazzi G, Franzini L, Derlindati E, Urbani S, Monti L, Gnudi L, Zavaroni I. Reduced Circulating Endothelial Progenitor Cell Number in Young Adult Hyperinsulinemic Healthy Men. Nutrition, Metabolism & Cardiovascular Diseases, Mar 2011. [Epub ahead of print]

• Dessapt C, Karalliedde J, Hernandez-Fuentes M, Prieto Martin P, Maltese G, Dattani N, Atkar R, Viberti GC, Gnudi L. Circulating Vascular Progenitor Cells in patients with Type 1 Diabetes and Microalbuminuria. Diabetes Care, 33(4):875-877, 2010.

• Dessapt C, Baradez MO, Hayward A, Dei Cas A, Thomas SM, Viberti GC, Gnudi L. Mechanical forces and TGFβ1 Reduce Podocyte Adhesion through a3β1 Integrin Downregulation. Nephrol Dial Transplant, 224(9):2645-55, 2009.

• Ku CH, White KE, Dei Cas A, Hayward A, Webster Z, Bilous R, Marshall SM, Viberti GC, and Gnudi L. Inducible overexpression of sFlt-1 in podocytes ameliorates glomerulopathy in diabetic mice. Diabetes, 57:2824-33, 2008.

• Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK for the AVOID Study Investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 358:2433-46, 2008.

• Long DA, Price KL, Ioffe E, Gannon CM, Gnudi L, White KE, Yancopoulos GD, Rudge JS, Woolf AS. Angiopoietin-1 therapy enhances fibrosis and inflammation following folic acid-induced acute renal injury. Kidney Int, 74:300-9, 2008.

• Gnudi L, Thomas S, Viberti GC. Mechanical forces in diabetic kidney disease: a trigger for impaired glucose metabolism. J Am Soc Nephrol, 18:2226-32, 2007.

• Davis B, Dei Cas A, Long D, White KE, Hayward A, Ku CH, Woolf A, Bilous R, Viberti GC, Gnudi L. Podocyte specific induced overexpression of angiopoietin-2 causes proteinuria and apoptosis of glomerular endothelia. J Am Soc Nephrol,18:2320-2329, 2007.

• Grønning LM, Tingsabadh R, Hardy K, Dalen KT, Jat PS, Gnudi L, Shepherd PR. Glucose induces increases in levels of the transcriptional repressor Id2 via the hexosamine pathway. Am J Physiol Endocrinol Metab, 290:E599-606, 2006.

• Gruden G, Setti G, Hayward A, Sugden D, Duggan S, Burt D, Buckingham R, Gnudi L, Viberti GC. Mechanical Stretch Induces Monocyte Chemoattractant Activity via an NF-{kappa}B-Dependent Monocyte Chemoattractant Protein-1-Mediated Pathway in Human Mesangial Cells: Inhibition by Rosiglitazone. J Am Soc Nephrol, 16:688-96, 2005.

• Burt DJ, Gruden G, Thomas SM, Tutt P, Dell'Anna C, Viberti GC, Gnudi L. P38 mitogen-activated protein kinase mediates hexosamine-induced TGFbeta1 mRNA expression in human mesangial cells. Diabetologia, 46:531-537, 2003.

• Gnudi L, Viberti G, Raij L, Rodriguez V, Burt D, Cortes P, Hartley B, Thomas S, Maestrini S, Gruden G. GLUT-1 overexpression: Link between hemodynamic and metabolic factors in glomerular injury. Hypertension, 42:19-24, 2003.

• Gruden G, Zonca S, Hayward A, Thomas S, Maestrini S, Gnudi L, Viberti GC. Mechanical stretch-induced fibronectin and transforming growth factor-beta1 production in human mesangial cells is p38 mitogen-activated protein kinase-dependent. Diabetes, 49:655-661, 2000.

• Gruden G, Thomas S, Burt D, Zhou W, Chusney G, Gnudi L, Viberti G. Interaction of angiotensin II and mechanical stretch on vascular endothelial growth factor production by human mesangial cells. J Am Soc Nephrol, 10:730-737, 1999.

• Gnudi L, Frevert EU, Houseknecht KL, Erhardt P, Kahn BB. Adenovirus-mediated gene transfer of dominant negative ras(asn17) in 3T3L1 adipocytes does not alter insulin-stimulated P13-kinase activity or glucose transport. Mol Endocrinol, 11:67-76, 1997.

• Gnudi L, Jensen DR, Tozzo E, Eckel RH, Kahn BB. Adipose-specific overexpression of GLUT-4 in transgenic mice alters lipoprotein lipase activity. Am J Physiol, 270:R785-R992, 1996.

• Gnudi L, Tozzo E, Shepherd PR, Bliss JL, Kahn BB. High level overexpression of glucose transporter-4 driven by an adipose-specific promoter is maintained in transgenic mice on a high fat diet, but does not prevent impaired glucose tolerance. Endocrinology, 136:995-1002, 1995.

• Shepherd PR, Gnudi L, Tozzo E, Yang H, Leach F, Kahn BB. Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue. J Biol Chem, 268:22243-22246, 1993.

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