Prof. Dr. Harry Holthöfer
External Senior Fellow (Marie S. Curie FCFP)
January - June 2016
Prof. Harry Holthofer MD, PhD graduated from the University of Helsinki, Finland and specialized in clinical microbiology/immunology. His hospital-based positions have included those of internal medicine, pulmology, pediatrics and occupational health.
The research of Prof Holthofer has focused on the biology of the glomerular filtration barrier, particularly in congenital nephrotic syndrome as well as kidney complications of diabetes. For that, various approaches ranging from molecular and cell biology, biochemistry combined with in vitro and in vivo analytical platforms have revealed new integral molecules constituting the functional kidney filtration barrier. The present main research line includes development of new methods for comprehensive understanding of urinary vesicles (including exosomes).
He became Professor and Director of the Technomedicum Research Centre from 2001-2006 in Finland and subsequently moved to Ireland to take up the Professorship and Chair of Bioanalytical Sciences at Dublin City University and to become Director of the Center for Bioanalytical Sciences in September 2006.
He has set up and directed several European Union (EU) funded programs focussing on diabetes, its biomarkers and new diagnostics and is presently setting up a wave of European collaborative grants to and from China.
Prof Holthofer is a founding member of the International Committee to Standardise Proteomics Methods in Kidney Research and European Kidney Health Initiative and serves in the boards of several research organisations including the European ERA-EDTA and got several international prices and acknowledgements of his expertise and achievements.
- Heikkilä E, Ristola M, Havana M, Holthöfer H, Lehtonen S: Trans-interaction of nephrin and Neph1/Neph3 induces cell adhesion that associates with decreased tyrosine phosphorylation of nephrin. Biochem J. 435:619-28, 2011
- Li Y, Zhou C, Shao X, Liu X, Guo J, Zhang Y, Wang H, Wang X, Li B, Deng K, Liu Q, Holthöfer H, Zou H. Hypertriglyceridemic waist phenotype and chronic kidney disease in a chinese population aged 40 years and older. PLoS One. 2014, 9:e92322
- Wasik AA, Koskelainen S, Hyvönen ME, Musante L, Lehtonen E, Koskenniemi K, Tienari J, Vaheri A, Kerjaschki D, Szalay C, Révész C, Varmanen P, Nyman TA, Hamar P, Holthöfer H, Lehtonen S. Ezrin Is Down-Regulated in Diabetic Kidney Glomeruli and Regulates Actin Reorganization and Glucose Uptake via GLUT1 in Cultured Podocytes. Am J Pathol. 2014,184:1727-39
- Musante L, TataruchD, Gu D, Benito-Martin D, CalzaferriG, Aherne S, Holthofer H A Simplified Method to Recover Urinary Vesicles for Clinical Applications. Sci Rep. 2014 Dec 23;4:7532. doi: 10.1038/srep07532
- Ravidà A, Kreivi M, Musante L, Miinalainen I, Byrne B, Saraswat M, Meleady P, ClynesM Holthofer H:Glycosylation Patterns in Rat Diabetic Nephropathy. Kidney Int. 2015 Jan 14. doi: 10.1038/ki.2014.387
Urinary Exosomes for Novel Diabetes Diagnostics
Proteinuria is a key manifestation of kidney diseases. It is a feared complication of diabetes and strongest predictor of cardiovascular emergencies. Glomerular epithelial cells, podocytes, are the main link between diabetes and proteinuria. These cells present with unique morphology, maintain body homeostasis and show huge vesicular transport activity.
Exosomes are recently found nano-microvesicles in many body fluids including urine, and contain a surprising variety of specific proteins, lipids and many distinct RNA species.
Here we propose a multifaceted approach to reveal the urinary exosome (UE) signature in diabetes, with special emphasis on uncovering the fundamental mechanisms in the podocytes and whether their distinct protein and RNA signatures can be used as biomarkers.
A variety of cell culture and existing experimental models will be compared in health vs. diabetic stress. Changes in UE transcriptomics, organellar proteomics and metabolomics will be collaboratively assayed with the equipment and top expertise readily available at the University of Freiburg. Advanced bioinformatics tools will be used to identify targets for potential monitoring and pathways involved in diabetes.
Major breakthroughs in disease monitoring and diabetes management with significant practical consequences can be expected.