Wenzheng Zhang, PhD
Areas of Study
- University of Texas1998MD Anderson Cancer CenterPhD
Kidney fibrosis is the hallmark of chronic kidney disease. Diabetes and hypertension are the first and second leading causes of chronic kidney disease. Dot1l encodes a methyltransferase specific for histone H3 lysine 79 and plays an important role in many biological processes including transcriptional regulation, cell cycle regulation, DNA repair, and leukemogenesis. This lab currently has three closely related projects about Dot1l function in kidney, using kidney samples from patients with various kidney diseases, genetically engineered mice, and cell lines as model systems.
The lab has generated Dot1lf/f mice and crossed them with Aqp2Cre driver to produce Dot1lAC mice in which Dot1l is specifically ablated in Aqp2-lineage cells. Dot1lAC vs. Dot1lf/f mice develop much more pronounced kidney fibrosis under various experimental settings. Dot1lAC and Dot1lf/f mice have been mated with various strains deficient in potential Dot1l downstream targets to determine if Dot1l deletion promotes kidney fibrosis by upregulating these targets.
Aqp2+ progenitor cells
Using loss of H3 K79 methylation and red fluorescence protein as tracing markers, Dr. Zhang's group has obtained preliminary data suggesting the existence of a new pool of renal progenitor cells expressing water channel Aquaporin 2 (Aqp2) during mouse development. Aqp2+ progenitor cells can give rise to all known types of cells forming the connecting tubule/collecting duct. Development of a Tamoxifen-dependent inducible Aqp2Cre driver is in process. The inducible Aqp2Cre driver will be combined with ''Rainbow'' mice, which harbor a multicolor (red, yellow, green, and blue) Cre-dependent reporter. These animals will be used to determine if individual Aqp2+ progenitor cells exist in adult mouse kidney, are multipotent, modulate collecting duct remodeling after injury or in response to metabolic stresses, and contribute to the pathogenesis of polycystic kidney disease.
Urinary biomarker of diabetic nephropathy
Molecular studies in this lab have identified water channel Aquaporin 5 (AQP5) as a new potential biomarker of diabetic nephropathy in mice and in humans. In humans, urinary AQP5 is significantly higher in diabetic nephropathy than in two control groups, and in diabetic nephropathy stage V than in stage III. Urinary AQP5 correlates with multiple other known risk factors of the disease and improves the clinical models in distinguishing diabetic nephropathy from normal controls and diabetic mellitus. The lab is collaborating with several laboratories in the world to conduct larger and longitudinal studies to validate if urine AQP5 has diagnostic and prognostic values as a new biomarker of diabetic nephropathy.
All of these ongoing projects are built on Dr. Zhang's previous studies, which identified Dot1l as an integrate component of aldosterone signaling network. This signaling network plays a key role in regulating Na+ transport and blood pressure through the epithelial Na+ channel.
View Wenzheng Zhang's articles on the National Institute of Health's PubMed website.