Erwin P Bottinger, MD
- PROFESSOR | Medicine, Nephrology
- PROFESSOR | Pharmacological Sciences
Research Topics:Apoptosis/Cell Death, Bioinformatics, Cell Biology, Diabetes, Fibrosis, Genomics, Growth Factors and Receptors, Kidney, Knockout Mice, Signal Transduction
Nuremberg General Hospital, University of ErIangen-Nuremberg
Cabrini Medical Center
Massachusetts General Hospital and Harvard Medical School
National Cancer Institute, National Institutes of Health
MD, Friedrich-Alexander Universitat School of Medicine, Erlangen-Nurember
Early pathomechanisms in diabetic nephropathy and non-diabetic kidney diseases
Millions of Americans are affected with chronic diabetic and non-diabetic kidney diseases that cause kidney failure (end stage renal disease). When kidneys fail, the average life expectancy is just over two years and survival depends on costly and disabling dialysis or transplantation treatments.
State-of-the-art genomics and bioinformatics approaches are used to discover and characterize new molecular targets and pathways associated with apoptosis, transdifferentiation, and fibrogenesis in specialized renal cells exposed to diabetic and other stresses. TGF-beta signaling pathways and targets are a major theme because TGF-beta is a key mediator of these processes.
Model systems used include renal cell culture and mouse models of diabetic and non-diabetic progressive renal disease. A new genomic medicine program aims at identification and validation of molecular biomarkers that predict progressive kidney disease in humans.
Wang W, Wyckoff JB, Frohlich VC, Oleynikov Y, Huttelmaier S, Zavadil J, Cermak L, Bottinger EP, Singer RH, White J, Segall J, Condeelis JS. Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling. Cancer Res 2002; 62: 6278-6288.
Yang YC, Piek E, Zavadil J, Xie D, Liang D, Heyer J, Pavlidis P, Kucherlapati R, Roberts AB, Bottinger EP. Hierarchical Model of Gene Regulation by TGF-B. Proc Natl Acad Sci USA 2003; 100(18): 10269-10274.
Nicolaou F, Teodoridis JM, Park H, Georgakis A, Farokhzad OC, Bottinger EP, Da Silva N, Rousselot P, Chomienne C, Ferenczi K, Arnaout MA, Shelley CS. CDllc gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras andjunD. Blood 2003 May 15; 101(10): 4033-4041.
Wang W, Wyckoff JB, Wang Y, Bottinger EP, Segall JE, Condeelis JS. Gene expression analysis on small numbers of invasive cells collected by chemotaxis from primary mammary tumors of the mouse. BMC Biotechnol 2003 Aug 12; 3(1): 13.
Liu X, Wen FQ, Kobayashi T, Abe S, Fang Q, Piek E, Bottinger EP, Roberts AB, Rennard SI. Smad3 mediates the TGF-beta-induced contraction of type I collagen gels by mouse embryo ibroblasts. Cell Motil Cvtoskeleton 2003 Mar; 54(3): 248-253.
Yoo J, Ghiassi M, Jirmanova L, Balliet AG, Hoffman B, Fomace Jr AJ, Liebermann DA, Bottinger EP, Roberts AB. TGF-beta-induced apoptosis is mediated by Smad-dependent expression of GADD45B through p38 activation. J Biol Chem 2003 Oct 31; 278: 43001-43007.
Goswami S, Sheets NL, Zavadil J, Chauhan BK, Bottinger EP, Reddy VN, Kantorow M, Cvekl A. The spectrum and range of oxidative stress responses of human lens epithelial cells to H202 insult: a cDNA microarray study. Invest Ophthalmol Vis Sci 2003; 44(5): 2084-2093.
Susztak K, Bottinger EP, Novetsky A, Liang D, Zhu Y, Ciccone E, Wu D, McCue P, Sharma K. Molecular Profiling of Diabetic Mouse Kidneys Reveals Novel Genes Linked toGlomerular Disease. Diabetes 2004; 53(3): 784-794.
Petkov PM, Zavadil J, Goetz D, Chu T, Carver R, Rogler CE, Bottinger EP, Shafritz DA, Dabeva MD. Gene expression pattern in hepatic stem/progenitor cells during rat fetal development using cDNA microarrays. Hepatology 2004 Mar; 39(3): 617-627.
Zavadil J, Cermak L, Soto-Nieves N, Bottinger EP. TGF-B /Smad3 co-activate HEY1 and Jagged 1/Notch 1 in Epithelial-to-Mesenchymal Transition. EMBO J 2004 Mar 10; 23(5): 1155-1165.