My lab is identifying molecular mechanisms that contribute to the development of acute kidney injury (AKI) and chronic kidney disease (CKD) utilizing animal models (experimental models of disease, conditional knockout mice) and in vitro (tubular and podocyte cell culture) methods. Our overall goal is to improve the understanding, diagnosis, and treatment of kidney disease using a translational bench-to-bedside approach.
The KEAP1 / NRF2 pathway plays a key role in cellular protection. In spite of this, the NRF2 enhancer, bardoxolone methyl, failed to show significant benefits in human CKD trials and may actually cause harm the kidney. We hypothesized that NRF2 effects are dependent on the kidney disease being studied, arguing against a one-size-fits-all approach. Indeed, our work revealed that the KEAP1 / NRF2 pathway protects against AKI-to-CKD progression but paradoxically worsens podocyte/glomerular injury and proteinuria. We are examining the mechanistic and cell-specific actions of NRF2 in the kidney.
In a new project, we are investigating the effect of renal sensory afferent and sympathetic efferent nerves on CKD progression. Renal nerve activity is both increased in CKD and may lead to effects that promote disease progression. Using mouse models, we are evaluating the role of renal denervation in CKD.
In other projects, we are investigating the mechanisms of microvascular rarefaction in kidney injury. We are using super-resolution ultrasound to evaluate changes in kidney vasculature in disease states in both animals and humans. We are also studying the role of MCP-1 and Wnt/beta-catenin on proteinuria and kidney fibrosis.
- BS, Georgetown University, 1999
- MD, University of Pittsburgh, 2007
- PhD, University of Pittsburgh, 2007
- Residency, Medicine, University of Pittsburgh Medical Center, 2010
- Fellowship, Renal-Electrolyte, University of Pittsburgh Medical Center, 2012
Education & Training
Bondi, C. D., Rush, B. M., Hartman, H. L., Wang, J., Al-Bataineh, M. M., Hughey, R. P., Tan, R. J. Suppression of NRF2 Activity by HIF-1a Promotes Fibrosis after Ischemic Acute Kidney Injury. Antioxidants. 2022; 11(9): 1810.
Mutchler, S. M., Hasan, M., Kohan, D. E., Kleyman, T. R., Tan, R. J. Deletion of the Gamma Subunit of ENaC in Endothelial Cells Does Not Protect against Renal Ischemia Reperfusion Injury. International Journal of Molecular Science. 2021; 22(20): 10914.
Rush, B. M., Bondi, C. D., Stocker, S. D., Barry, K. M., Small, S. A., Ong, J., Jobbagy, S., Stolz, D. B., Bastacky, S. I., Chartoumpekis, D. V., Kensler, T. W., Tan, R. J. Genetic or pharmacologic Nrf2 activation increases proteinuria in chronic kidney disease in mice. Kidney International. 2021; 99(1): 102-116.
Chen, Q., Yu, J., Rush, B. M., Stocker, S. D., Tan, R. J., Kim, K. Ultrasound super-resolution imaging provides a noninvasive assessment of renal microvasculature changes during mouse acute kidney injury. Kidney International. 2020; 98(2): 355-365.
Tan RJ, Li Y, Rush BM, Cerqueira DM, Zhou D, Fu H, Ho J, Beer Stolz D, Liu Y. Tubular injury triggers podocyte dysfunction by ß-catenin-driven release of MMP-7. JCI Insight. 2019; 4(24): e122399.
Rush BM, Small SA, Stolz DB, Tan RJ. An Efficient Sieving Method to Isolate Intact Glomeruli from Adult Rat Kidney. J Vis Exp. 2018; (141): e58162.
Jobbagy S, Tan RJ. Nitrolipids in kidney physiology and disease. Nitric Oxide. 2018; S1089-8603(18): 30006-5.
Tan RJ, Chartoumpekis DV, Rush BM, Zhou D, Fu H, Kensler TW, Liu Y. Keap1 hypomorphism protects against ischemic and obstructive kidney disease. Scientific Reports. 2016; 6: 36185.
Tan RJ, Zhou D, Xiao L, Zhou L, Li Y, Bastacky SI, Oury TD, Liu Y. Extracellular Superoxide Dismutase Protects against Proteinuric Kidney Disease. Journal of the American Society of Nephrology : JASN. 2015; 26(10): 2447-59.
Tan, RJ, Zhou, D, Zhou, L, Liu, Y. Wnt/ß-catenin signaling and kidney fibrosis. Kidney International Supplements. 2014; 4(1): 84-90.
- Young Investigator Award, Society for Free Radical Biology and Medicine, 2004
- Lawrence Reardon Professionalism Award, Internal Medicine Residency Program, UPMC, 2010
- Frank J. Bruns Teaching Award, 2012
- Young Physician-Scientist Award, The American Society for Clinical Investigation, 2016
- Excellence in Education Award, Small Group (PBL) Facilitator for Renal-Electrolyte Course, 2020
- Excellence in Education Award, Small Group (PBL) Facilitator for Renal-Electrolyte Course, 2022
Title: Effect of renal nerves on chronic kidney disease
Role: Principal Investigator
Funding Agency: NIDDK
Grant Number: R01 DK131991
Start Year: 2022
End Year: 2027
Title: The Role of Nrf2 in Proteinuric Chronic Kidney Disease
Role: Principal Investigator
Funding Agency: Veterans Health Administration (Merit Award)
Grant Number: IPA BX005680
Start Year: 2022
End Year: 2026
Title: Pros and Cons of Nrf2 in FSGS Pathogenesis
Role: Principal Investigator
Funding Agency: USMRAA / DOD
Grant Number: RES PR211476
Start Year: 2022
End Year: 2026
Title: RNA binding proteins in end-organ autoimmune pathology
Role: Co-Investigator
Funding Agency: NIAID
Grant Number: R01 AI162616
Start Year: 2022
End Year: 2027
Title: RNA binding proteins in end-organ autoimmune pathology
Role: Co-Investigator
Funding Agency: NIAID
Grant Number: R01 AI162616
Start Year: 2022
End Year: 2027
