Gang Xi, PhD
Gang Xi is a researcher at the University of North Carolina (UNC)’s Kidney Center and Division of Nephrology and Hypertension, Department of Medicine, the University of North Carolina at Chapel Hill. He completed his doctoral training with Dr. Marcia Hathaway in the Department of Animal Sciences at the University of Minnesota at Twin Cities. His postdoctoral fellowship was performed in the lab of Dr. David Clemmons in the UNC Department of Medicine. External funding support for Dr. Xi’s research has been provided by the National Institutes of Health. 
Gang Xi, PhD
Research Summary
Our research focuses on the pathogenesis of autoimmune kidney diseases, particularly in anti-neutrophile cytoplasmic autoantibody (ANCA) glomerulonephritis, Minimal Change Disease (MCD), and Focal Segmental Glomerulosclerosis (FSGS). To understand the underlying mechanisms which are responsible for developing these diseases, we focus on proteins level alternations, such as protein-protein interactions, protein post-translation modifications, including phosphorylation, oxidation and ubiquitination. Identification autoantigens that are responsible for these diseases not only provide potential novel strategies to treat glomerulonephritis but also make the precise diagnosis and individualized treatment plan possible.
In addition, in collaboration with Dr. Roy-Chaudhury’s research group, we perform vascular access studies, including creating different animal disease models, such as uremic or/and diabetic mouse, or tissue specific protein knockout mouse, and smooth muscle cells phenotypic switch regulation with an intention to provide the best vascular access solution for the individual patient who needs dialysis service.
Antigens post-translation modifications play vital roles in mediating pathogenesis of autoimmune diseases because these modifications not only can provide novel chemical groups to serve as haptens for generating neo-antibodies but also can induce the conformation changes of antigens to expose novel epitopes, leading to generation of neo-antigens. In our drug-induced ANCA vasculitis study, we clearly demonstrated that hydralazine was able to form hydrazone adducts on MPO, an important antigen of ANCA vasculitis, when the carbonyl modification pre-exists, which normally occurs under oxidative conditions. This modification also resulted in MPO heavy chain conformation changes to generate neo-antibodies, mainly IgM, to attack the targets, including kidneys, small vessels and lungs. Pathogenesis of hydralazine-associated ANCA-vasculitis and may illuminate a certain set of mechanisms of autoimmunity in general Related publications: Xi G, Mclnnis EA, Lardinois O, Hu P, Poulton JS, Free ME, Chen DP, Zeitler EM, Wu EY, Orzechowski NM, Derebail VK, Jennette JC, Falk RJ. Sequential carbonyl derivatives and hydrazone adduct formation on myeloperoxidase contribute to development of ANCA vasculitis. J Clin Invest. 2025 Feb 27;135(8):e178813. doi: 10.1172/JCI178813. PMID: 40020049; PMCID: PMC11996859.
Post-translation modifications of certain functional proteins play critical roles in mediating multiple intracellular signal transduction and cellular biological functions. Modifications include but are not limited to oxidation, phosphorylation, ubiquitination, etc., which mediate normal physiological or pathophysiological functions. These modifications have been detected in a variety of normal cellular settings or under disease conditions. Phosphorylation and ubiquitination of adapter proteins play vital roles in mediating physiological and pathophysiological vascular smooth muscle cell functions Related publications: Xi G*, Lamba SA, Mysh, M, Poulton JS*. Oxidative Stress Contributes to Slit Diaphragm Defects Caused by Disruption of Endocytosis. Kidney International Reports. 2024 Feb 9(2). PMID: 38344712 (Co-corresponding authors) Xi G, Shen X, Wai C, White MF, Clemmons DR. Hyperglycemia induces vascular smooth muscle cell dedifferentiation by suppressing insulin receptor substrate-1-mediated p53/KLF4 complex stabilization. J Biol Chem. 2019 Feb 15;294(7):2407-2421. doi: 10.1074/jbc.RA118.005398. Epub 2018 Dec 21. PMID: 30578299; PMCID: PMC6378959. Xi G, Shen XC, Wai C, Clemmons DR. Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained Src activation in response to insulin-like growth factor-I. J Biol Chem. 2013 May 31;288(22):15641-53. doi: 10.1074/jbc.M113.456046. Epub 2013 Apr 23. PMID: 23612968; PMCID: PMC3668724 Xi G, Shen X, Maile LA, Wai C, Gollahon K, Clemmons DR. Hyperglycemia enhances IGF-I-stimulated Src activation via increasing Nox4-derived reactive oxygen species in a PKCζ-dependent manner in vascular smooth muscle cells. Diabetes. 2012 Jan;61(1):104-13. doi: 10.2337/db11-0990. Epub 2011 Dec 6. PMID: 22148072; PMCID: PMC3237650
The plasticity of VSMCs is a very important feature for remodeling vessels. We focus on the differences between arterial SMCs and venous SMCs, and explore the underlying mechanisms which are responsible for the differences of clinical symptoms between arteries and veins. Our studies clearly demonstrated that not only different signaling pathways were used to mediate physiological or pathophysiological activities in arteries and veins but also, in the same signaling pathway, different sets of genes are utilized to mediate similar cellular functions. These studies provide potential druggable targets to treat artery or vein specific vascular diseases under different conditions. Difference and similarity of proteins expression in arterial porcine smooth muscle cells (ApSMCs) and venous porcine smooth muscle cells (VpSMCs). Related publications: Lee KA, Li W, Uriyanghai U, Wai C, Su H, Yang A, Li L, Sudarsanam VA, Poulton JS, Roy-Chaudhury P, Xi G*. Bulk RNA Sequencing Reveals Signature Differences in Key Cell Signaling Pathways Between Porcine Venous and Arterial Smooth Muscle Cells. Int J Mol Sci. 2025 Dec 11;26(24):11948. doi: 10.3390/ijms262411948. PMID: 41465376 (*Corresponding author) Su H, Uriyanghai U, Wai C, Arteaga EC, Wan H, Adam KP, Sudarsanam VA, Haddad SO, Yang A, Li L, Bahnson EM, Poulton JS, Roy-Chaudhury P, Xi G*. Uremic serum exposure leads to differential phenotypic switch in porcine arterial and venous smooth muscle cells. Am J Physiol Renal Physiol. 2025 Dec 1;329(6):F809-F819. doi: 10.1152/ajprenal.00217.2025. Epub 2025 Oct 25. PMID: 41138212 (*Corresponding author) Li L, Uriyanghai U, Wai C, Yuan H, Livingston EW, Bahnson EM, Sudarsanam V, Haddad S, Roy-Chaudhury P, Griffith BE, Xi G*. Temporal evolution of hemodynamics in murine arteriovenous fistula: a micro-CT based computational fluid dynamics study. PLoS Comput Biol. 2025 Aug 18;21(8):e1012985. PMID: 40825001 (*Corresponding author) Arteaga EC, Wai C, Uriyanghai U, Rudraraju M, Su H, Sudarsanam VA, Haddad SO, Poulton JS, Roy-Chaudhury P, Xi G*. Characterization of Protein Expression and Signaling Pathway Activation That May Contribute to Differential Biological Functions in Porcine Arterial and Venous Smooth Muscle Cells. Int J Mol Sci. 2025 Mar 28;26(7):3110. doi: 10.3390/ijms26073110. PMID: 40243809 (*Corresponding author)
