Guangping Chen, PhD

Research Associate Professor

Emory University School of Medicine

Office: Department of Physiology

Phone: 404-727-1371 : Lab 404-727-1371

Fax: 404-727-2648


Additional Contact Information

Mailing Address:

Emory University School of Medicine

615 Michael Street
605N Whitehead Research Building

Atlanta, GA 30322


Education: From PhD/MD to current position.
       PhD., Fudan University School of Medicine, China

Research Area:
           Renal physiology; urine concentration mechanism; urea transporter


In mammals, the production of concentrated urine requires a hypertonic medulla and an osmolarity gradient along the cortico-medullary axis. Sodium and urea are the two major solutes that contribute to the medullary osmolarity gradient in kidney. The major mechanism for delivering urea to the inner medullary interstitium is urea reabsorption from the terminal inner medullary collecting duct (IMCD). This permits urea to accumulate in the inner medullary interstitium and contributes to the osmotic driving force that pulls water out of the tubular fluid, thus concentrating urine. The UT-A1 urea transporter, expressed in the apical membrane of the principal cells in the terminal IMCD, is the most important urea transporter for renal urea reabsorption and plays a critical role in the urine concentrating mechanism. The principal interest of my lab is to investigate the molecular mechanism of kidney UT-A1 urea transporter regulation under both physiological and pathological conditions. Currently, my lab focuses on:
(1) Regulation of the UT-A1 urea transporter by ubiquitination. Ubiquitin modulation is crucial in the physiological regulation of many cellular processes. By a yeast two-hybrid assay, we discovered that UT-A1 interacts with a pair of ubiquitination related enzymes; an E3 ubiquitin ligase MDM2 and a de-ubiquitinating enzyme USP24. These findings open up the exciting possibility of a distinct and novel mechanism for UT-A1 regulation: the ubiquitin-proteasome pathway. Recently we have new finding that UT-A1 could be processed by either mono- or poly-ubiquitination depending on UT-A1 protein modifications (e. g., phosphorylation). Unlike the basal condition where UT-A1 is subject to poly-ubiquitination and proteasome-mediated protein degradation, activation of UT-A1 by forskolin (FSK) induces UT-A1 mono-ubiquitination and lysosomal degradation. This finding suggests that activation of the cAMP/PKA pathway (by vasopressin or FSK), causing UT-A1 phosphorylation, also triggers the protein ubiquitination and degradation machinery for UT-A1. This negative feedback of UT-A1 activation reveals an important physiological mechanism of how the cells in vivo attenuate the hormonal response and return to the basal condition after vasopressin stimulation.

(2) Small proteins and kidney urea transport regulation. The general idea of this project is that during trafficking and recycling of UT-A1, the protein must interact with a host of accessory proteins that are involved in these processes. Over the past few years, by yeast two-hybrid assay, immunoprecipitation and amino acid sequence analysis, we identified a body of small molecular weight proteins directly interacting with UT-A1, such as lipid raft protein caveolin-1, phospho-specific binding protein 14-3-3?, small GTPase protein Rab14 and Arf5, and glycan binding protein galectin. The physiological significance of this project is to draw the scenario of how kidney urea transport is regulated at molecular levels by these adaptor proteins. Our long-term goal is to screen and develop small-molecule modulators of these proteins that could affect UT-A1 function in vivo for potential therapeutic interventions for total body fluid overloaded diseases such as hypertension, congestive heart failure, cirrhosis, and nephrotic syndrome.

(3) UT-A1 regulation by N-linked glycosylation. N-linked glycosylation is a key post-translational modification that can affect the structure and function of glycoproteins. UT-A1 is heavily glycosylated with up to ~30% of the 117 kDa mature mass comprising of glycan structures. Like many membrane proteins such as AQP2, NKCC2, ENaC, etc., N-linked glycosylation plays important roles in regulating UT-A1 membrane trafficking and protein stability. However, the underlying mechanisms how glycosylation affects these processes are largely unknown. We found that under diabetic conditions (STZ diabetic rats), not only is UT-A1 protein abundance increased (known for years), but the glycan structure of UT-A1 is also changed. UT-A1 glycans become highly sialylated, fucosylated and branched. This suggests that the alteration of the glycan sugar structure could be one of the important mechanisms of the enhanced urea permeability in IMCD in diabetes. We also found that a group of glycan binding proteins called galectins participate in glycan regulation of UT-A1. Based on these findings, we propose that UT-A1 activity can be modulated by altering protein glycosylation or galectin expression and galectin-UT-A1 interactions. Loss/change of specific glycans results in loss of galectin-glycan lattice formation and alteration of renal urea transport functions.