• Ph.D. in Clinical Medicine - Semmelweis University of Budapest, December, 2004 (summa cum laude honors).
  • Master of Sciences in Bioengineering - Faculty of Chemical Engineering, Technical University of Budapest, Hungary, 1999

Research Interests

Our laboratory has a general interest in redox biology, with emphasis on diabetes, insulin resistance and diabetic nephropathy (DN). Our research focuses on the exact free radical mechanisms that can play a role in the pathogenesis of these conditions, ultimately contributing to insulin resistance or leading to tissue damage and to complications.

Currently we are interested in:

- Understanding the redox signaling roles of reactive lipids and mitochondrial lipid hydroperoxides;

- Understanding the specific role of redox signaling in an important complication of diabetes: diabetic nephropathy. For this project we use high fat diet models, diabetic models with significant renal pathology, transgenic and pharmacological approaches and kidney cell lines studying proximal tubular cells and podocytes. Loss of podocytes - which are important cells in the integrity of the filtration barrier in the kidney - is characteristic to obesity and diabetic nephropathy. Loss of podocytes will result in proteinuria and renal complications. Treatments for hyperglycemia and high blood pressure do not stop podocyte loss, indicating that other important factors must exits. Little is known about redox signaling mechanisms and the role of reactive lipids in controlling podocyte survival and death. Identifying these mechanisms has high clinical significance as it may help designing targeted therapies to prevent diabetic nephropathy or similar proteinuric diseases.

Besides podocytes, a second project deals with proximal tubular cells and their mitochondrial metabolism. This is because a) tubular cell injury correlates best with mortality in diabetic nephropathies, b) eventually almost all kidney diseases culminate into tubulointerstitial fibrosis. New research from us and others indicate that tubular injury may also be a primary event in DN rather than just a secondary consequence. Prevention here therefore would be of high importance as well.

Through the use of in vivo electron spin resonance (EPR) methodologies we are able to specifically detect increased free radical production in tissues or cells. Low temperature EPR from frozen samples can be used to evaluate the integrity of various protein complexes, for example the different components of the electron transport chain. In addition, the combination of EPR and other techniques (e.g. confocal microscopy, immunohistochemistry, XF24 extracellular flux analyzer) provides an additional conceptual innovation to our studies.

Research in this laboratory is funded by the Pennington Foundation, and through grant support by NIDDK 1R01-DK115749-01A1 (PI: Krisztian Stadler), and by an NIDDK/DiaComp Pilot and Feasibility grant 14GHSU1393 (through P30-DK076169) (PI: Krisztian Stadler).

Department: Oxidative Stress and Disease

Selected Publications

  1. Kruger C, Nguyen TT, Breaux C, Guillory A, Mangelli M, Fridianto KT, Kovalik JP, Burk DH, Noland RC, Mynatt R, Stadler K. Proximal Tubular Cell-Specific Ablation of Carnitine Acetyl-Transferase Causes Tubular Disease and Secondary Glomerulosclerosis. Diabetes 2019. doi: 10.2337/db18-0090. [Epub ahead of print]  *selected to be featured in Faculty1000Prime as special significance to the field
  2. Kruger C, Burke SJ, Collier JJ, Nguyen TT, Salbaum JM, Stadler K. Lipid peroxidation regulates podocyte migration and cytoskeletal structure through redox sensitive RhoA signaling. Redox Biol 2018. 248-254. doi:10.1016/j.redox.2018.02.024. Epub 2018 Mar 6.
  3. Wicks SE, Nguyen TT, Breaux C, Kruger C, Stadler K.
    Diet-induced obesity and kidney disease – in search of a susceptible mouse model. Biochimie 2016, 124: 65-73
  4. Stadler K, Goldberg IJ, Susztak K. The evolving understanding of the contribution of lipid metabolism to diabetic kidney disease. Curr Diab Rep. 2015, 15:40.
  5. Ruggiero C, Elks CM, Kruger C, Cleland E, Addison K, Noland RC, Stadler K. Albumin-bound fatty acids but not albumin itself alter redox balance in tubular epithelial cells and induce a peroxide-mediated redox-sensitive apoptosis. Am J Physiol Renal Physiol. 2014 Apr 15;306(8):F896-906
  6. Ansenberger-Fricano K, Ganini D, Mao M, Chatterjee S, Dallas S, Mason RP, Stadler K, Santos JH, Bonini MG.The peroxidase activity of mitochondrial superoxide dismutase.Free Radic Biol Med. 2013 Jan;54:116-24.
  7. Stadler K.Oxidative stress in diabetes. Adv Exp Med Biol. 2012;771:272-87.
  8. Kadiiska MB, Bonini MG, Ruggiero C, Cleland E, Wicks S, Stadler K. Thiazolidinedione treatment decreases oxidative stress in spontaneously hypertensive heart failure rats through attenuation of inducible nitric oxide synthase-mediated lipid radical formation.Diabetes. 2012 Mar;61(3):586-96.
  9. Mao M, Varadarajan S, Ansenberger-Fricano K, Fernandes DC, Tanaka LY, Fukai T, Laurindo FR, Mason RP, Vasquez-Vivar J, Minshall RD, Stadler K, Bonini MG. Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway.
    Free Radic Biol Med. 2011 Oct 7. epub ahead of print.
  10. Ruggiero C, Ehrenshaft M, Cleland E, Stadler K. (2011) High fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production. Am J Physiol Endocrinol Metab 300: E1047-58.
  11. Levesque S, Taetzsch T, Lull ME, Kodavanti U, Stadler K, Wagner A, Johnson JA, Duke L, Kodavanti P, Surace MJ, Block ML.(2011) Diesel exhaust activates & primes microglia: Air pollution, neuroinflammation & regulation of dopaminerg neurotoxicity. Environ Health Perspect 119(8):1149-55.
  12. Vandanmagsar B, Youm YH, Ravussin A, Galgani J, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. (2011) The Cryopyrin/NALP3/NLRP3 Inflammasome Instigates Obesity-Induced Autoinflammation and Insulin Resistance. Nat Med. 17:179-88.
  13. Stadler K. (2011) Peroxynitrite-driven mechanisms in diabetes and insulin resistance – the latest advances. Curr Med Chem 18:280-90.
  14. Stadler K, Bonini MG, Dallas S, Jiang JJ, Mason RP, Kadiiska MB (2008) Involvement of inducible nitric oxide synthase in hydroxyl radical-mediated lipid peroxidation in streptozotocin-induced diabetes. Free Radic Biol Med 45: 866-74.
  15. Stadler K, Bonini MG, Dallas S, Mason RP, Kadiiska MB (2008) Direct evidence of iNOS-mediated in vivo free radical production and protein oxidation in acetone-induced ketosis. Am J Physiol Endocrinol Metab 295: E456-E462.
  16. Stadler K, Bonini MG, Lautenschlager S, Corbett J, et al. (2008) Constitutive nitric oxide synthase activation is a significant route for nitroglycerin-mediated vasodilation. Proc Natl Acad Sci U S A. 105: 85699-74.
  17. Nakai K, Kadiiska MB, Jiang JJ, Stadler K, Mason RP. (2006) Free radical production requires both inducible nitric oxide synthase and xanthine oxidase in LPS-treated skin. Proc Natl Acad Sci U S A.103: 4616-21.
  18. Stadler K, Jenei V, Somogyi A, Jakus J. (2005) Beneficial effects of aminoguanidine on the cardiovascular system of diabetic rats. Diabetes Metab. Res. Rev. 21: 189-96.
  19. Stadler K, Jenei V, Somogyi A, von Bölcsházy G, Jakus J. (2003) Increased nitric oxide levels as an early sign of premature aging in diabetes. Free Radic. Biol. Med. 35: 1240-51.