Our Research Projects

The Devarajan Lab is currently working on several observational studies and clinical trials. Learn more about our projects below.

Current Research Projects

Implications of the novel AKI biomarker NGAL in non-critically ill settings, in retrospective and prospective clinical trails

Summary

We are conducting studies on clinical samples from patients with urinary tract infections, kidney stones, diabetic nephropathy, nephrotoxicity, and chronic kidney disease progression, to determine the diagnostic accuracy of NGAL in predicting or excluding each of these clinical outcomes.

Collaborators

William R. DeFoor Jr., MD, MPH, Division of Urology
Amy S. Shah, MD, MS, Division of Endocrinology

Dissecting the role of nephrogenic transcription factor SOX4 in the AKI to CKD transition, using nephron segment-specific inducible ablation mouse models

Summary

We have engineered mouse models with ablation of SOX4 in the proximal or the distal tubule. In our models of AKI to CKD transition, we have identified an initial protective role of SOX4 but a paradoxical worsening in later stages. We are examining the molecular basis of these changes, which might provide novel pathways and therapeutic targets.

Funding

  • National Institutes of Health

Collaborators

Matthew Kofron, PhD, Division of Developmental Biology

Dissecting the role of the novel fibroblast-specific molecule Gucy1a1 in the generation and evolution of chronic kidney disease progression, using fibroblast-specific inducible ablation mouse models

 

Validating the novel urinary RAIL biomarkers in lupus nephritis progression and response to therapy in clinical trials

Summary

We have identified and validated 6 urinary biomarkers (termed RAIL) that early identify lupus nephritis severity, progression, and response to therapies. We are collaborating with several industry partners to assess the RAIL response in their clinical trials of novel agents.

Collaborators

Hermine I. Brunner, MD, MSc, Division of Rheumatology

Creating a novel multiplex RAIL assay for clinical deployment

Summary

We are validating the Luminex and Mesoscale platforms for multiplex measurement of RAIL biomarkers in a single sample, and offering the test for routine clinical use as a commercial Laboratory Derived Test.

Funding

  • FALK Award

Collaborators

Hermine I. Brunner, MD, MSc, Division of Rheumatology

Validating the optimal dosing of mycophenolate mofetil for treatment of lupus nephritis in prospective clinical trials

Summary

This is a multi-center prospective clinical trial that examines the efficacy of mycophenolate when dosed using pharmacologic monitoring versus standard weight-based dosing. We have recruited about 15 sites nationally, and enrollment has begun.

Funding

  • National Institutes of Health

Collaborators

Hermine I. Brunner, MD, MSc, Division of Rheumatology

Past Research Projects

Implications of the DAXX / ASK1 / JNK Pathway in Acute Renal Failure

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

  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases

Collaborator

Alex Kuan, MD, PhD, Division of Developmental Biology

Immunofluorescence images of kidneys.
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.

Early Prediction of Lupus Nephritis Using Advanced Proteomics

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

  • Department of Defense

Collaborator

Hermine Brunner, MD, MSc, Division of Rheumatology

SELDI-TOF proteomic profiling.
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). 

Glomerulosclerosis in Human FSGS and Mouse Models

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.

Funding

  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases

Collaborator

S. Steven Potter, PhD, Division of Developmental Biology

Laser-captured glomeruli.
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.

Novel Biomarkers in Cardiac Surgery to Detect Acute Kidney Injury

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

  • National Institutes of Health
  • National Heart, Lung, and Blood Institute

Collaborators

Catherine Dent Krawczeski, MD, the Heart Institute

Chirag Parikh, MD, PhD, FACP, Yale University

Ancillary Studies in the Natural History of Acute Kidney Injury

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.

Funding

  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases

Collaborators

Catherine Dent Krawczeski, MD, the Heart Institute

Chirag Parikh, MD, PhD, FACP, Yale University

Nephrology Center of Excellence

The Pediatric Nephrology Center of Excellence at Cincinnati Children’s Hospital Medical Center is one of only three in the nation supported by the National Institutes of Diabetes & Digestive & Kidney Diseases. The Center of Excellence serves as a national resource for conducting ground-breaking research into pediatric kidney disease.