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Apoptosis is a major mechanism leading to tubule cell death in early acute kidney injuries. We are investigating the DAXX / ASK1 / JNK signal transduction mechanism as a unique cell death pathway following early injury; this may provide a target for innovative therapies. The specific aim of this project is to identify the contributions of this pathway to structural and functional kidney damage, using a variety of in vitro and in vivo manipulations.
Funding Source: NIH / NIDDK
Collaborator: Alex Kuan, MD, PhD, Division of Developmental Biology
This project aims to identify novel noninvasive biomarkers of lupus nephritis. Such biomarkers could facilitate the clinical evaluation of innovative therapeutic approaches, and could reveal the mechanics of the disease’s pathology. The specific aim of this project is to identify and validate biomarker patterns in lupus nephritis using proteomic profiling techniques.
Funding Source: Department of Defense
Collaborators: Hermine Brunner, MD, MSc, Division of Rheumatology
We intend to identify and validate distinct transcriptomic profiles in laser-captured glomeruli from humans and animal models of focal segmental glomerulosclerosis. This research could help reveal novel disease mechanisms, therapeutic targets and biomarkers for clinical use.
Collaborators: S. Steven Potter, PhD, Division of Developmental Biology
Through this project we intend to validate NGAL, cystatin C and IL-18 as predictive biomarkers of acute kidney injury and its adverse outcomes after cardiac surgery. This is a multicenter observational study.
Funding Source: NIH / NHLBI
Collaborators: Catherine Dent Krawczeski, MD, the Heart Institute; Chirag Parikh, MD, PhD, FACP, Yale University
This project aims to define the long-term outcomes of acute renal injury after cardiac surgery and to identify the role of early biomarkers in predicting the outcomes. This is a multicenter observational study.
Figure for Project 1 - click to enlarge
Figure for Project 1. Immunofluorescence images of mouse kidney after ischemia reperfusion injury (left panels) or transplanted human cadaveric kidney (right panels), showing colocalization of DAXX and apoptotic TUNEL-positive tubule epithelial cells. The asterisk illustrates tubules that are negative for both.
Figure for Project 2 - click to enlarge
Figure for Project 2. SELDI-TOF proteomic profiling of urine reveals distinct protein peaks in patients with Class IV and Class V lupus nephritis that are absent from controls (top two panels).
Figure for Project 3 - click to enlarge
Figure for Project 3. Laser-captured glomeruli will be subjected to cDNA microarray analysis. Genes differentially expressed in affected versus unaffected glomeruli will be correlated with histopathology and clinical outcomes.
Figure for Project 4 - click to enlarge
Figure for Project 4. Immunofluorescence image of kidney from a subject with acute kidney injury, stained for NGAL, showing tubule cells laden with the protein in a punctuate cytoplasmic distribution. The serendipitous appearance of this protein in the urine has provided for a powerful noninvasive early biomarker of acute kidney injury.
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