Debra Hullett
Faculty > Debra Hullett
Debra Hullett
Professor, Surgery
hullett@surgery.wisc.edu
Organ System/Disease Focus
Chronic Allograft Injury/Chronic Kidney Disease
Aligned Research Focus
Epithelial to mesenchymal transition. Vascular remodeling
Research Description
Our lab has strong collaborations with the Odorico and Hoch laboratories and part of the Immunology Core. Our current research focuses on chronic allograft injury (CAI) that results in tubular atrophy (TA) and interstitial fibrosis (IF) and is the leading cause of long-term graft failure in kidney transplant recipients.
TA/IF results when tubular epithelial cells (TEC) and interstitial fibroblasts transition to mesenchymal myofibroblasts (EMT) cells. This process leads to replacement of TEC by matrix resulting in reduced kidney mass and a concomitant decline in kidney function. We have noted that this process occurs both in vitro in a rat proximal tubular cell line and in vivo in the setting of CAI.
EMT is attenuation by 1,25(OH)2D3 in both instances. CAI is further characterized by a proinflammatory cytokine and monocyte/macrophage cellular response. These responses dramatically increase reactive oxygen species and increased the oxidative stress (OS) burden that has also been associated with EMT.
1,25(OH)2D3 is immunoregulatory and has anti-oxidant properties as well. Our observations together with those of others suggest that 1,25(OH)2D3,s actions in the setting of chronic allograft injury are multi-factorial and that its use as adjunct therapy may significantly improve long-term renal allograft function.
Selected References
Kahan BW, Jacobson LM, Hullett DA, Ochoada JM, Oberley TD, Lang KM, Odorico JS. Pancreatic precursors and differentiated islet cell types from murine embryonic stem cells - An in vitro model to study islet differentiation. Diabetes 52(8):2016-2024. 2003.
Hullett DA. Hematopoietic stem cells; pluripotent stem cells or transdifferentiation? Transplantation 74(9):1220-22. 2002.
Fernandez LA, Hatch EW, Armann B, Odorico JS, Hullett DA, Sollinger HW, Hanson MS. Validation of larger particle flow cytometry for the analysis and sorting of intact pancreatic islets. Transplantation 80:(6) 729-737. 2005.