Establishment and Development:
Kidney diseases pose a significant health threat to the public. It has been reported that CKD affects more than 10% of the general population worldwide. One of the major challenges in the treatment of CKD is the restoration of kidney function and structure, which involves intricate systemic processes and requires the utilization of various approaches, including the discovery of new drugs, stem cell therapy, and the application of organoids. Therefore, developing new therapies for CKD depends on interdisciplinary collaboration and cutting-edge technology. Our lab takes multidisciplinary approaches to perform comprehensive and multi-dimensional research on kidney diseases and has made significant breakthroughs in elucidating the pathophysiology of kidney injury, analyzing protein structures, identifying targets, synthesizing potential drugs, and culturing diverse organoids. We have published over 150 papers in high-level peer-reviewed journals such as Cell Metabolism, Nature Communications, Kidney International, and JASN. We aim to integrate multiple research approaches to discover risk populations, target genes, molecular mechanisms, and innovative interventions for Kidney diseases.
Team Members:
Our team is composed of three doctoral supervisors including Dr. Fan Yi, Dr. Tang Wei, Dr. Yusheng Xie. Prof. Yi is the leader of Science Fund for Creative Research Groups of the National Natural Science Foundation of China, winner of the National Science Fund for Distinguished Young Scholars. Dr. Yi’s research interests are focused on investigating kidney diseases pathophysiology, especially the kidney regional immunity and epigenetic regulation mechanism. Dr. Yi has published more than 120 articles, with 8327 citations and an H-index of 49. The published manuscripts have garnered considerable interest and acclaim within the international scholarly community. The manuscript published in Cell Metabolism was distinguished as the cover article and was accompanied by an editorial commentary. Furthermore, the study published on Nature Communications received commendation from F1000. Three articles published on the Kidney International were honored with special editorial commentaries.
Dr. Tang’s research interest focuses on regulation DNA damage and repairment in kidney disease. The goal is to explore the novel strategies for acute kidney injuries. Dr. Tang has published several high-level papers such as Science, Molecular Therapy.
Dr. Xie is mainly engaged in the investigation of chemical tools for recognition and intervention of the epigenetic regulation. His discovery led to the development of a Sirt2 drug screening platform and the pursuit of targeted drug discovery. Furthermore, Dr. Xie underscored the critical role of innovative chemical biology tools in the fundamental theoretical exploration of post-translational modification (PTM)-related protein machinery, as well as in the translational application of strategic interventions.
Research Areas:
Our research emphasizes the role of local immune responses, metabolic homeostasis regulation, and epigenetic modifications in renal diseases. The study systematically elucidates the impact of various immunity-related and metabolism-related molecules on kidney diseases. Moreover, the research conducts systematic studies on the functions of novel GPCRs in renal damage, especially in renal aging, providing a significant theoretical and experimental foundation for identifying new drug targets and developing preventive and therapeutic strategies for kidney diseases.
Research Achievements:
Our research team is dedicated to unraveling kidney disease mechanisms, emphasizing local immune regulation, epigenetic regulation mechanisms, and GPCR signaling. These studies aim to identify new drug targets and provide theoretical and experimental foundations for the prevention and treatment of kidney diseases. We were the first to clarify the involvement of pattern recognition receptors like NOD2 in podocyte damage and insulin resistance, potentially triggering kidney-specific immune responses and podocyte injury (Kidney international 2013, Hypertension 2013). This research was highlighted in Kidney International with editorial commentary. Further studies showed that JAML exacerbates podocyte damage by disrupting lipid metabolism, with these findings featured on the cover of Cell Metabolism. The team's exploration of kidney-specific immune responses, particularly the function of resident memory T cells, has opened new therapeutic avenues for kidney diseases. (Molecular Therapy 2020, Kidney international 2017).
Using cryo-electron microscopy, We've detailed the roles of specific GPCR subtypes in kidney injury, uncovering changes in adhesion-class GPCR receptors and steroid hormone patterns during kidney repair processes. The related results were published in Nature Chemical Biology and JASN, providing insights for GPCR-targeted drug development in kidney diseases.
Notably, we also conduct series research on epigenetic modification mechanism in kidney disease. We identified HDAC4 and Sirt6 as the key enzymes involved in kidney diseases and participated podocyte injury in diabetic nephropathy and hypertension-induced kidney damage. Related results have published Kidney International and Nature Communications, featured by F1000 recommendation. Related results also have published in Circulation Research, which was selected as the cover article and honored by editorial commentary.
Main Publications:
Selected publications in last 5 years (*represents the corresponding authors).
1. Fu Y#, Sun Y#, Wang M, Hou YF, Huang W, Zhou D, Wang ZY, Yang ST, Tang W, Zhen JH, Li YJ, Wang XJ, Liu M, Zhang Y, Wang B, Liu GY, Yu X, Sun J, Zhang C, and Yi F*. Elevation of JAML Promotes Diabetic Kidney Disease by Modulating Podocyte Lipid Metabolism. Cell Metabolism, 2020; 32(6):1052-1062. (Cover paper, this article was honored by an editorial commentary, Citations: 75).
2. Guo J, Wang Z, Wu J, Liu M, Li M, Sun Y, Huang W, Li Y, Zhang Y, Tang W, Li X, Zhang, C, Hong F, Li N, Nie J, and Yi F*. Endothelial SIRT6 Is Vital to Prevent Hypertension and Associated Cardiorenal Injury Through Targeting Nkx3.2-GATA5 Signaling. Circulation Research, 2019;124(10):1448-1461. (Cover paper, this article was highlighted in “In this issue” and was honored by an editorial commentary, Citations: 106).
3. Liu M, Liang K, Zhen J, Zhou M, Wang X, Wang Z, Wei X, Zhang Y, Sun Y, Zhou Z, Su H, Zhang C, Li N, Gao C, Peng J, and Yi F*. Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling. Nature Communications, 2017;8(1):413. (F1000 recommendation, Citations: 230).
4. Lin H#, Xiao P#, Bu RQ#, Guo SC#, Yang Z#, Yuan DP#, Zhu ZL, Zhang CX, He QT, Zhang C, Ping YQ, Zhao RJ, Ma CS, Liu CH, Zhang XN, Jiang D, Huang SH, Xi YT, Zhang DL, Xue CY, Yang BS, Li JY, Lin HC, Zeng XH, Zhao H, Xu WM, Yi F*, Liu ZM*, Sun JP*, Yu, X*. Structures of the ADGRG2–Gs complex in apo and ligand-bound forms. Nature Chemical Biology. 2022;18(11):1196-1203.
5. Zhan P, Zhang Y, Shi, WC, Liu XH, Qiao Z, Wang ZY, Wang XJ, Wu JC, Tang W, Sun Y, Zhang Y, Zhen JH, Shang J, Liu M*, Yi F*. Myeloid-derived growth factor deficiency exacerbates mitotic catastrophe of podocytes in glomerular disease. Kidney international, 2022;102(3):546-559. (This article was highlighted in “In this issue”).
6. Zhang Y, Yang Y, Yang F, Liu X, Zhan P, Wu J, Wang X, Wang Z, Tang W, Sun Y, Zhang Y, Xu Q, Shang J, Zhen J, Liu M, Yi F*. HDAC9-mediated epithelial cell cycle arrest in G2/M contributes to kidney fibrosis in male mice. Nat Commun. 2023 May 25;14(1):3007.
7. Huang W, Wang BO, Hou YF, Fu Y, Cui SJ, Zhu JH, Zhan XY, Li RK, Tang W, Wu JC, Wang ZY, Wang M, Wang XJ, Zhang Y, Liu M, Xie YS, Sun Y, Yi F*. JAML promotes acute kidney injury mainly through a macrophage-dependent mechanism. JCI Insight. 2022 Jun 16;7(14):e158571.
8. Li L, Tang W, Zhang Y, Jia M, Wang L, Li Q, Han Q, Peng X, Xie Y, Wu J, Wang Z, Zhen J, Wang X, Liu M, Sun Y, Zhang C, Yi F*. Targeting tissue-resident memory CD8+ T cells in the kidney is a potential therapeutic strategy to ameliorate podocyte injury and glomerulosclerosis. Mol Ther. 2022 Aug 3;30(8):2746-2759
9. Xie Y, Du S, Liu Z, Liu M, Xu Z, Wang X, Kee JX, Yi F*, Sun H, Yao SQ. Chemical Biology Tools for Protein Lysine Acylation. Angew Chem Int Ed Engl. 2022 May 16;61(21):e202200303.
10. Jia M, Li L, Chen R, Du J, Qiao Z, Zhou D, Liu M, Wang X, Wu J, Xie Y, Sun Y, Zhang Y, Wang Z, Zhang T, Hu H, Sun J, Tang W, Yi F*. Targeting RNA oxidation by ISG20-mediated degradation is a potential therapeutic strategy for acute kidney injury. Mol Therapy. 2023 Oct 4;31(10):3034-3051.
11. Zuo FW, Liu ZY, Wang MW, Du JY, Ding PZ, Zhang HR, Tang W, Sun Y, Wang XJ, Zhang Y, Xie YS, Wu JC, Liu M, Wang ZY, Yi F*. CCDC92 promotes podocyte injury by regulating PA28α/ABCA1/cholesterol efflux axis in type 2 diabetic mice. Acta Pharmacol Sin. 2024 Jan
12. Wu JC, Wang XJ, Zhu JH, Huang XY, Liu M, Qiao Z, Zhang Y, Sun Y, Wang ZY, Zhan P, Zhang T, Hu HL, Liu H, Tang W, Yi F*. GPR97 deficiency ameliorates renal interstitial fibrosis in mouse hypertensive nephropathy. Acta Pharmacol Sin. 2023 Jun;44(6):1206-1216.
13. Zuo F, Wang Y, Xu X, Ding R, Tang W, Sun Y, Wang X, Zhang Y, Wu J, Xie Y, Liu M, Wang Z, Yi F*. CCDC92 deficiency ameliorates podocyte lipotoxicity in diabetic kidney disease. Metabolism. 2024 Jan;150:155724
14. Liu M, Zhang Y, Zhan P, Sun W, Dong C, Liu X, Yang Y, Wang X, Xie Y, Gao C, Hu H, Shi B, Wang Z, Guo C, Yi F*. Histone deacetylase 9 exacerbates podocyte injury in hyperhomocysteinemia through epigenetic repression of Klotho. Pharmacol Res. 2023 Dec;198:107009.
15. 16. Su Z, Li Y, Lv H, Cui X, Liu M, Wang Z, Zhang Y, Zhen J, Tang W, Wang X, Yi F*. CLEC14A protects against podocyte injury in mice with adriamycin nephropathy. FASEB J. 2021 Jul;35(7):e21711.
16. Cui X, Shi E, Li J, Li Y, Qiao Z, Wang Z, Liu M, Tang W, Sun Y, Zhang Y, Xie Y, Zhen J, Wang X, Yi F*. GPR87 promotes renal tubulointerstitial fibrosis by accelerating glycolysis and mitochondrial injury. Free Radic Biol Med. 2022 Aug 20;189:58-70.
Facilities & Resources:
Our team is supported by the Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity. We boast multi-color fluorescence flow cytometry, real-time quantitative PCR instrument, laser confocal microscope, single crystal X-ray diffractometer, small animal micro CT imaging analysis system, fluorescence microscope, laser confocal microscope, laser confocal high content imaging analysis system, scanning electron microscope, transmission electron microscope, two-photon microscope, atomic force microscope, live cell workstation, panoramic tissue multispectral imaging and quantitative analysis system, biacore biomolecular interaction analysis system, mass spectrometry instrument, single crystal X-ray diffractometer, 400 MHz fully digital superconducting nuclear magnetic resonance spectrometer, cryo-electron microscopy, Seahorse Cell Energy Analysis System XFe96, small animal Metabolism System, small animal nuclear magnetic resonance Imaging instrument, SPF grade IVC mouse feeding system and other related facilities. In addition, several national key laboratories and open laboratories available in our university. Generally, our team is equiped with many large equipments and basic instruments required for performing above studies.
Recreational Activities:
There are many types of outdoor and indoor activities in our university. We have modern gymnasium, concert hall and various social groups such as badminton, basketball, running. Our university often holds interesting sports, sets up several sports and entertainment and competitions suitable for all teachers and students to participate, strengthens the physical exercise, and improves the physical health. In addition, variety show is regularly held in Baotu Spring Campus to inherit the fine tradition of Qilu Medicine of the century-old "Broad Wisdom and Truth-seeking". Many types of professional development workshops are held to communicate with famous researchers in different fields.
Other Features:
Totally, there are more than 30 master and doctoral graduates in our team. In our lab, joint lab meeting is held each week. Journal club is organized by graduates actively to learn the lastest references. We usually hold a spring outing every year.
Contact:
For more information or inquiries, please contact us at wangxiaojie@sdu.edu.cn or visit our website at https://www.en.bms.sdu.edu.cn/Departments/Department_of_Pharmacology.htm.
