Rujun Gong Lab

Rujun Gong, MD, PhD — Major Research Interests

Pathology magazine coverMy long-term research interests focus on understanding the pathogenesis and developing novel therapies of glomerular diseases, in particular nephrotic glomerulopathies. More specifically, the recent efforts of my research team focus on the roles of the melanocortinergic signaling pathway and the glycogen synthase kinase 3b signaling pathway in glomerular diseases. Another interest of my research lies in deciphering the mechanisms responsible for acute and chronic injury, repair and regeneration of solid organs, including the kidney, liver and heart. In addition, my research team is also interested in the pathogenic mechanisms of renal fibrogenesis and inflammation as well as epistasis in common kidney diseases and immunopathogenesis of lupus nephritis.


On-going research studies

  1. The role of  glycogen synthase kinase 3b (GSK3b) signaling in kidney disease

This line of research is an outreach of my postdoctoral research work, which made an important finding that the kidney protective activity of hepatocyte growth factor is mediated by GSK3b inhibition. In this context, I further explored how kidney-specific GSK3b gene knockout as well as small molecule inhibitors affects kidney dysfunction, tubular injury, glomerular damage or proteinuria in murine models of acute and chronic kidney injuries, including obstructive nephropathy, non-steroid anti-inflammatory drugs induced nephrotoxicity, adriamycin nephropathy, nephrotoxic serum nephritis and lupus nephritis. We were the first group to successfully breed a strain of mice with GSK3b gene knockout specifically in postnatal kidney tubules (Laboratory Investigation-LI cover story) and also another strain of mice with podocyte specific conditional knockout of GSK3b gene (Journal of the American Society of Nephrology-JASN cover story). By using these transgenic animals, my team managed to examine the molecular mechanisms accounting for acute kidney injury, chronic renal fibrosis as well as podocytopathy, a disease of podocytes that drives the development and progression of proteinuria, glomerulosclerosis and loss of kidney function. In particular, my group has recently defined the role of GSK3b in mediating podocyte cytoskeleton disorganization (American Journal of Pathology cover story), mitochondria dysfunction and the Nrf2 antioxidant response in glomerular disease. Moreover, we have tested diverse small molecule inhibitors of GSK3b and FDA-approved drugs with GSK3b inhibitory activities in kidney disease models. Our latest study demonstrated that lithium, a mood stabilizer that has been safely used for over 50 years as the first line treatment for bipolar affective disorders, confers a pro-reparative effect on kidney injury at low doses that ameliorates acute kidney injury and protects against glomerular damage and proteinuria. This line of research attracted enormous public interest and has been highlighted by a number of news media. These studies have been funded by the NIH R01 grant since 2011.

  1. The role of melanocortinergic pathway in glomerular disease

Laboratory Investigation coverMy early research in glomerular disease pointed out to me a paramount challenge of clinical nephrology practice, i.e. refractory nephrotic syndrome. As the first FDA-approved treatment for nephrotic syndrome, ACTH was ever used in the 1950s for childhood nephrotic syndrome, but fell out of favor with the advent of oral glucocorticoids. However, recent clinical observations demonstrating the successful use of ACTH in steroid-resistant nephrotic glomerulopathies suggest a unique anti-proteinuric activity of ACTH that is steroidogenic-independent and may be attributable to its melanocortinergic activity. This has rekindled my interest in melanocortin therapy for proteinuric glomerulopathies and even other kidney diseases. In this regard, our studies indicate that kidney cells, like podocytes and renal tubular cells, express abundant melanocortin receptors and are direct effector of melanocortin hormone system. Melanocortin peptide therapy is able to exert a direct kidney effect, resulting in protection against acute kidney injury as well as glomerular injury and proteinuria. These studies have been published in a number of high-impact journals, including Nature Reviews Nephrology, Kidney InternationalAdvances in Chronic Kidney Disease and Pediatrics. Moreover, this line of research has been funded by grants from non-profit foundations, industry and lately by the US NIH R01 grant support.


CURRENT RESEARCH SUPPORT, TRAINING GRANTSJASN Cover

1. Grant Title: The Melanocortinergic pathway in glomerular disease.
Agency: NIH/NIDDK R01DK114006
Request Period: 08/15/2017~ 05/31/2022
Role: Principal Investigator

PAST RESEARCH SUPPORT, TRAINING GRANTS

  1. Grant Title: Therapeutic targeting of GSK3beta: A novel approach for podocyte protection.
    Agency: NIH NIDDK R01 DK092485
    Funding Period: 09/01/2011~ 08/31/2016
    Role: Principal Investigator 
  2. Grant Title: An in Vivo study of treprostinil, a prostacyclin analog, in the prevention of ischemia-reperfusion injury to the kidney.
    Agency: NIH U54GM115677 Advance-CTR (Clinical Translational Research) at Brown University
    Funding Period: 07/01/2017~ 06/30/2018
    Role: Principal Investigator   
Last Updated: 6/27/22