Wenzheng Zhang, PhD

Kidney fibrosis

The lab has generated Dot1l^f/f mice and crossed them with Aqp2Cre driver to produce Dot1l^AC mice in which Dot1l is specifically ablated in Aqp2-lineage cells. Dot1l^AC vs. Dot1l^f/f mice develop much more pronounced kidney fibrosis under various experimental settings. Dot1l^AC and Dot1l^f/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.