Fries laboratory

Grants

Research has been and is continuously supported by different funding sources outside and inside the university.

Outside funding sources:

  • Marga und Walter Boll Stiftung
  • Private donations

Inside funding sources:

  • Köln Fortune 
  • Imhoff-Stiftung
Research background Prof. Dr. Jochen Fries

In the experimental thesis (Prof. Thoenes, Pathology, Univ. Clinic, Mainz, Germany) a backleak of tubular fluid caused by tubular necrosis in the S3 segment due to a continued ischemic environment was shown by light and electron microscopy as cause of prolonged acute renal failure. A morphometric analysis of glomerular epithelial damage in proteinuric renal disease (1980-1984) demonstrated that only a small amount of all glomerular epithelial podocytes is altered in proteinuric/hematuric diseases in adults and children independent of the degree of proteinuria. Studying mechanism of proteinuria in a DFG-funded project at the Brigham and Women’s Hospital, Boston, MA, USA (Pathology, Laboratory of Prof. Dr. H. Rennke; 1984-1987) an immune complex mediated versus hypertensive model of glomerular disease was established showing the importance of the location immune complex deposition versus hemodynamic forces as determinants for progressive glomerular damage. A molecular biology project at the Harvard School of Public Health (Public Health; Prof D. Wirth, 1987-1989) in molecular mycobacteriology provided the basis for future studies at the molecular level, establishing DNA probes for diagnostic analyses for M. avium and the genus Mycobacteria. Studies in molecular vascular research (PDGF-transgenic mouse; cloning and characterisation of E-selectin and vascular cell adhesion molecule-1; Pathology, Brigham and Women’s Hospital; Prof. T. Collins; 1987-1997) as well as working as a consultant for experimental animal research (Prof. J. Halperin; Lab. of Transport Physiology; Harvard Medical School; 1994-1997) became important steps for future studies. In Köln (Pathology; since 1997) a microdissection method for analysing glomerular disease in formalin-fixed, paraffinized biopsies was established funded by the DFG.

The availability of virus-targeted gene delivery as well as the stem cell technology have been part of the research repertoire for renal and cardiac disease through scientific ollaboration. The participation in the program of the DSO (Deutsche Stiftung Organtransplantation) in pre-transplant organ evaluation as well as the evaluation of non-allocated livers and kidneys have led to an intense interest in the problems of organ transplantation.

Over the last 5 years, research efforts have focussed on the role of endothelin in progressive renal disease and renal tumors. The signalling pathway via the ET-A-receptor and a cytoplasmic transcription complex consisting NF-kBp65, MAPKp38 and PKCα migrating into the nucleus has been analysed in normal and tumorous proximal tubule cells/human tumors.

Current interests of the Fries laboratory

  • Chronic Renal Disease 
  • Cardiac/Vascular Disease
  • Molecular Therapy/Transplantation/Stem Cell Technology
Future projects

  • Activation of nuclear p16
  • Role of an ET-1 induced microRNA in proteinuric renal disease
  • Role of PKC in oncocytic transformation
  • Molecular analysis of a subtype of clear cell renal carcinoma

Publications

1. Kidney | Molecular Nephropathology

  • Thoenes W, Fries J. Micromorphology of the nephron in experimental temporary ischemic kidney and in human acute renal failure. In: Schilling A, ed. Acute renal failure: pathophysiology, its significance for intrarenal surgery and prevention. Muenchen: Zuckschwerdt, 1983; 1-23.

  • Weber M, Koehler H, Fries J, Thoenes W, Meyer zum Büschenfelde K-H. Rapidly progressive glomerulonephritis in IgA/IgG cryoglobulinemia. Nephron 1985; 41: 258-261.

  • Poralla T, Trautman F, Rumpelt H-J, Fries J, Eckhardt R, Hütteroth TH, Meyer zum Büschenfelde K-H. A case of Sjoegren's syndrome with severe anemia due to myelitis. Klin Wochenschr 1986, 64: 92-95.

  • Fries JWU, Rumpelt H-J, Thoenes W. Alterations of glomerular podocytic processes in immunologically mediated glomerular disorders - a morphometric analysis. Kid Int 1987; 32:742-748.

  • Fries JWU, Mendrick DL, Rennke HG. Determinants of the expression of immune complex mediated glomerular injury using ferritin as an exogenous planted antigen. 
    Kid Int 1988; 34:333-345.
  • Fries JWU, Sandstrom D, Meyer TW, Rennke HG. Glomerular hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis in the rat. Lab Invest 1989; 60:205-218.
  • Fries JWU, Collins T. Platelet-derived growth factor expression in a transgenic model. Kid Int 1992; 41: 584-589.

  • Khachigian LM, Collins T, Fries JWU. Nuclear factor-kappa B mediates induction of vascular cell adhesion molecule-1 in glomerular mesangial cells. Biochem Biophys Res Comm 1995; 206: 462-467.

  • Khachigian LM, Collins T, Fries JWU. N-acetyl cysteine blocks mesangial VCAM-1 and NF-kB expression in vivo. Am J Path 1997; 151: 1225-1229.

  • Stoffel MP, Pollok M, Fries JWU, Baldamus CA. Radiation nephropathy after radiotherapy in metastatic medullary thyroid carcinoma. Nephrol Dial Transplant 2001, 16: 1082-1083.

  • Fries JWU, Pakula A, Roth T, Dienes H-P, Odenthal M.

  • Quantitation of inflammatory and proliferative genes as disease markers in laser-microdisseceted, formalin-fixed and paraffinized glomeruli from human renal biopsies. Gene Function and Disease 2002; 3: 98-108

  • Fries JWU, Roth T, Dienes H-P, Weber M, Odenthal M. A novel evaluation method for paraffinized human renal biopsies using quantitative analysis of microdissected glomeruli and VCAM-1 as marker of inflammatory mesangial activation. Nephrology, Dialysis and Transplantation 2003; 18: 710-716

  • Mattheus T, Fries J, Weber M, Schulze-Lohoff E. Glomeruläre Proteinurie bei Hantavirus-Nephritis. Med Klinik 99: 223-227, 2004

  • Benenson E, Fries JWU, Pollok M, Ruppert A, Heilig B. High-dose azathioprine pulse regimen as a new option of induction therapy in patients with Wegener’s granulomatosis and lupus nephritis refractory or indolent to cyclophosphamide. Clin Rheumatology 24:251-157, 2005

  • Lehmann E, Fries J WU, Schulze-Lohoff E, Weber M. A rare case of birenal malakoplakia with renal failure (German with English abstract). Deutsch Med. Wschr. 130: 1-4, 2005

  • Gerstung M, Roth T, Dienes H-P, Licht C, Fries JWU. Endothelin-1 induces NF-kappa B via two independent pathways in human rean ltubular epithelial cells. American Journal of Nephrology 2007, Vol. 27, Issue 3, 294-300

  • von Brandenstein M; Abety A N, Depping R, Roth T, Koehler M, Dienes H-P, Fries JWU. A p38-p65 transcription complex induced by endothelin-1 mediates signal transduction in cancer cells. Biochemica et Biophysica Acta (BBA)- Molecular Cell Research 2008, Vol. 1783, Issue 9, 1613-1622

  • Beck BB, N Laube, S Habbig, M Feldkötter, Fries JWU, B Hoppe. The Case: A boy with recurrent stones. Kid Int 2008, 74: 133-134

  • Gross O, Weber M, Fries JWU, Müller G-A. Living donor kidney transplantation from relatives with mild urinary abnormalities in Alport syndrome: long-term risk, benefit and outcome. Nephrology, Dialysis and Transplantation 24: 1626-1630, 2009.

  • Gerstung von Brandenstein M, Depping R, Schäfer E, Dienes H-P, Fries JWU. Endothelin-1 induced Protein kinase C α regulates nuclear pri-microRNA 15a release. Biochim Biophys Acta. 2011 Oct;1813(10):1793-802

  • von Brandenstein M, Pandarakalam JJ, Herden J, Braun G, Wendland K, Dienes H-P , Engelmann U, Fries JWU. MicroRNA 15a, inversely correlated to PKC α, is a potential marker to differentiate between benign versus malignant renal tumors in biopsies and in urine samples. The American Journal of Pathology,Volume 180, Issue 5, May 2012, Pages 1787–1797

  • Melanie von Brandenstein, Claudia Richter, Jochen W.U. Fries, MicroRNAs: Small but amazing, and their association with endothelin, Life Sciences, Volume 91, Issues 13–14, 15 October 2012, Pages 475–489

  • von Brandenstein M, Schlosser M, Richter C, Depping R, Fries JWU, ETS-dependent p16INK4a and p21waf1/cip1 gene expression upon endothelin-1 stimulation in malignant versus and non-malignant proximal tubule cells, Life Scinces, 2012 Oct 15;91(13-14):562-71

  • H Loeser, M von Brandenstein, A Herschung,  M Schlosser, Buettner R, JWU Fries Endothelin-1 influences Multiple Drug Resistance in the human renal proximal tubule via microRNA 133a downregulating the MRP2 transporter, Life Scinces, under review

  • Licht Chr, Gross O, Mertens PR, Scheffler M, Weber M, Odenthal M, Fries JWU.
    ET-receptor blockade delays progression of tubulointerstitial fibrosis in a mouse model of Alport syndrome. Kid Int 2011 (in preparation)
2. Heart | Vascular Research

  • Mika H, Bumb P, Fries J. Rupture of supraaortal neck arteries due to lesions caused by tracheal tube. J Laryngeol Otol 1984; 98,5: 509-517.

  • Bork K, Fries J, Hoede N, Korting G-W, Dienes P. Undifferenziertes kutanes Angiosarkom des Kopfes: Identifizierung mit Endothel-Marker Ulex europaeus agglutinin I. Der Hautarzt 1985; 36: 341-346.

  • Cybulski MI, Fries JWU, Williams AJ, Sultan P, Davis VM, Gimbrone MA Jr, Collins T. Alternative splicing of human VCAM-1 in activated vascular endothelium.
    Amer J Path 1991; 138:815-820.

  • Cybulski MI, Fries JWU, Williams AJ, Sultan P, Eddy R,Byers M, Shows T, Gimbrone MA Jr, Collins T. Gene structure, chromosomal location and basis for alternative mRNA splicing of the human VCAM-1 gene. Proc Natl Acad Sci 1991; 88: 7859-7863

  • Collins T, Young R, Mendoza A, Fries J, Williams A, Sultan P, Bonthron D. Regulation of PDGF expression in vascular cells. In: Gottlieb AI, Langville BL, Fedoroff S, eds.; Altschul symposium series, vol I, Atherosclerosis: cellular and molecular interactions in the artery wall. New York and London: Plenum, 1991.

  • Williams AJ, Atkins RC, Fries JWU, Gimbrone MA Jr, Cybulski MI, Collins T. Nucleotide sequence of rat vascular cell adhesion molecule-1 cDNA. Biochem Biophys Acta 1992; 1131: 214-216

  • Fries JWU, Williams AJ, Atkins RC, Newman W, Lipscomb MF, Collins T. Expression of VCAM-1 and E-Selectin in an in vivo model of endothelial activation. Am J Path 1993; 143,3: 725-737.

  • Khachigian LM, Fries JWU, Benz MW, Bonthron DT, Collins T.

  • Novel cis-acting elements in the human platelet-derived growth factor

  • B-chain core promoter that mediate gene expression in cultured vascular endothelial cells. J Biol Chem 1994; 269: 22647-22656.

  • Krueger K, Deissler P, Coburger S, Fries JWU, Lackner K. How thrombus model impacts the in vitro study of interventional thrombectomy procedures. Invest Radiol 39: 641-648, 2004

  • Heckenkamp J, Lieder K, Lang E, Aleksic M, Bendel MS, Gawenda M, Fries JWU, Brunkwall JS. Radiation therapy induced modulation of wound healing at experimental vein graft anastomoses. Eur J Vasc Endovasc Surg 29: 463-469, 2005

  • Wieneke H, Neumann T, Breuckmann F, Hunold P, Fries JWU, Dirsch O, Erbel R. Non-compaction Kardiomyopathie. Herz 30: 571-574, 2005

  • Huntgeburt M, Lindner M, Fries JWU, Hoppe UC. Hypereosinophilic syndrome associated with acute necrotizing myocarditis and cardiomyopathy. Z Kardiol 94: 761-766, 2005

  • Dodos F, Schneider T, Fries JWU, Hoppe U. Benign cardiac tumor in a patient with lung malignancy. Clin Res Cardiol. 96: 628 – 631 (2007).

  • Welsandt G, Fries JWU, W Konen, S Roters. Exophthalmus nach Exzision eines orbitalen Hämangioperizytoms vor 18 Jahren. Ophthalmologe 2008, 105: 274-277

  • Sparwel J, Vantler M, Caglayan E, Kappert K, Fries JWU , Dietrich H, Bohm M, Erdmann E, Rosenkranz S. Differential effects of red and white wines on inhibition of the platelet-derived growth factor receptor: impact of the mash fermentation. Cardiovasc Res 81: 758-770 (2009).

  • Dashkevich A, Bloch W, Antonyan A, Goebel, Fries JWU; Schlensak C, Beyersdorf F, Geissler HJ. Immunhistochemical study or remodelling of myocardial lymphatic and blood microvascular structures in terminal heart failure: differences between ischemic and dilated cardiomyopathy. Lymphology 43: 110-117, 2010.
3. Molecular Therapy | Transplantation | Stem cell Technology

  • Philipp J, Unruh M, Wagener A, Fries JWU, Gottstein C. The in vivo coagulating activity of soluble tissue factor is selectively enhanced on tumor endothelium by endotoxin. Arteriosklerosis, Thrombosis and Vascular Research 2003; 23: 905-910

  • Paul A, Treckmann J, Saad S, Hoffmann J, Fries J, Nagelschmidt M. Primärfunktion warmischämisch geschädigter Schweinenieren nach retrograder Sauerstoffpersufflation hypothermer Lagerung oder Maschinenperfusion. Chirurgisches Forum 23:407-409, 2003

  • Kuhn-Regnier F, Bloch W, Tsimpoulis I, Reisman M, Dagktekin O, Jeschkeit-Schubbert S, Funcke C, Fries JWU, Addicks K, deVivie ER, Fischer JH. Coronary oxygen persufflation for heart preservation in pigs: analyses of endothelium and myovytes. Transplantation 77: 28-35, 2004.

  • Dienst A, Grunow A, Unruh M, Rabausch B, ,Nör JE, Fries JWU, Gottstein C. Specific vascular occlusion of murine and human tumor vasculature by VCAM-1 targeted recombinant fusion proteins. J Natl Cancer Inst. 97: 733-747, 2005

  • Hirschfeld J, Maurer J, Juung D, Kwiecinski M, Khimji Al Karim, Dienes H P, Fries JWU, Odenthal M. Targeting myofibroblasts in model systems of fibrosis by an artifical α-smooth muscle –actin promoter hybrid. Mol Biotechnology 43: 121-129 (2009) Müller-Ehmsen J, Krausgrill B, Burst V, Schenk K, Neisen UC, Fries JWU, Fleischmann BK, Hescheler J, Schwinger RHG. Effective engraftment but poor mid-term persistance of mononuclear and mesenchymal bone marrow cells in rat myocardial infarction. J Mol Cell Cardiol 41: 876-884, 2006

  • Kolossov E, Bostani T, Roell W, Breitbach M, Pillekamp F, Nygren JM, Sasse P, Rubenchik O, Fries JWU, Wenzel D, Geisen C, Xia Y, Lu Z, Duan Y, Kettenhofen R, Jovinge S, Bloch W, Bohlen H, Welz A, Hescheler J, Jacobson SE, Fleischmann BK. Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restore contractile function to the infarcted myocardium. J Exp Med 203: 2315-2327, 2006

  • Geissler HJ, Dashkevich A, Fischer UM, Fries JWU, Kuhn-Regnier F, Addicks K, Mehlhorn U, Bloch W. First year changes of myocardial lymphatic endothelial markers in heart transplant recipients. Eur J Cardio-Thoracic Surg 2005; 29: 767-771, 2006

  • Breitbach M, Bostani T, Roell W, Xia Y, Dewald O, Nygren Jm, Tiemann K, Fries JWU, Tiemann K, Bohlen, H, Hescheler J, Welz A, Bloch W, Jacobson SE, Fleischmann BK. Potential risks of bone marrow cell transplantation into infarcted heart. Blood 110: 1362-1369, 2007

  • Tossios P, B Krausgill, M Schmidt, T Fischer, M Halbach, Fries JWU, S Fahnenstich, P Frommolt, I Heppelmann, A Schmidt, K Schomäcker, JH Fischer, W Bloch, U Mehlhorn, RHG Schwinger, J Müller-Ehmsen. Role of balloon occlusion for mononuclear bone marrow cell deposition after intracoronary injection in pigs with reperfused myocardial infarction. Eur Heart J 29: 1911 – 1921 (2008).

  • Dashkevich A, Bloch W, Antonyan A, Fries JWU, Geissler HJ. Morphological and quantitative changes of the intial myocardial lymphatics in terminal heart failure. Lymphatic Research AND Biology 7: 21 – 27 (2009).

  • Rey J, Wirges U, Dienes H P, Fries JWU. Hepatic steatosis in organ donors – disparity between surgery and histology? Transplantation Proceedings 41: 2557-2560 (2009).

  • Schievenbusch S, Strack I, Scheffler M, Nischt R, Coutelle O, Hösel M, Hallek M, Fries JW, Dienes HP, Odenthal M, Büning H. Combined paracrine and endocrine AAV9 mediated expression of hepatocyte growth factor for the treatment of renal fibrosis. Mol. Ther., 18:1302-97 (2010).

  • Burst VR, Gillis M, Pütsch F, Herzog R, Fischer JH, Heid P, Müller-Ehmsen J, Schenk K, Fries JW, Baldamus CA, Benzing T. Poor cell survival limits the beneficial impact of mesenchymal stem cell transplantation on acute kidney injury. Nephron Exp. Nephrol., 114:e107-16 (2010).

  • Rey W J and Fries JWU. The liver biopsy during organ donation. In: Liver Biopsy / Book 2", ISBN 978-953-307-883-0 (2011).
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