- Co-Director, Basic Sciences
- Co-Director, Annual Acute Kidney Injury Symposium
Clinical Interests
Glomerular Disease, Acute Kidney Injury, Microvascular Rarefaction, Amyloidosis (https://cardiacamyloidosis.pitt.edu/)
Educational Interests
Medical School Teaching, Graduate School Teaching
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.
- 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 Science2021. 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.