Mingui Fu, Ph.D.
Department(s) of Biomedical Sciences
UMKC School of Medicine
Education and Background
Xian Medical University, China
Ph.D. - Peking University Health Science Center
Fellowship - Morehouse School of Medicine
Fellowship - University of Texas Southwestern Medical Center
Meet Mingui Fu
Specialties and Research/Medical Interests
Biochemistry, Cell Biology, Pathology, Regulatory mechanisms of septic shock, Signal transduction in macrophage activation, RNA metabolism in immune regulation, Negative regulation of Toll-like receptor signaling, Molecular signaling of vascular endothelial inflammation, injury and repair, Novel therapeutic targets for human inflammatory diseases including atherosclerosis, sepsis and viral infection
The Roles of CCCH-Zinc Finger Proteins in the Regulation of Inflammation.
Nearly 60 CCCH-zinc finger proteins have been identified in humans and mice. These proteins are involved in the regulation of multiple steps of RNA metabolism, including mRNA splicing, polyadenylation, transportation, translation, and decay. Several CCCH-zinc finger proteins, such as tristetraprolin, Roquin and MCPIP1, are crucial for many aspects of immune responses via targeting mRNA degradation and other mechanisms. Others are involved in the regulation of cell differentiation and cancer cell growth. In the past ten years, we have been working on a novel CCCH-zinc finger containing protein, MCPIP1, in the regulation of both innate and adaptive immunity. Using transgenic and knockout mouse models, we are studying the physiological role and mechanisms of MCPIP1 in inflammatory response and immunity and the involvement of MCPIP1 in septic shock, atherosclerosis and autoimmune diseases.
Novel Molecular Regulators in Vascular Endothelial Inflammation, Injury and Repair.
Vascular endothelium is a multifunctional and critical interface between blood stream and vascular wall. Meanwhile, vascular endothelium is also the largest endocrine, paracrine and metabolic organ. Recent studies suggest that there is endothelial dysfunction at the early stage of cardiovascular diseases and stroke caused by atherosclerosis, hypertension and diabetes. In addition, the initial event in bacterial and viral infection-caused multi-organ injury is vascular endothelial damage and dysfunction. So that vascular endothelial inflammation and dysfunction is a common pathological step and basis for cardiovascular diseases and stroke and acute organ injury. Improving the function of vascular endothelium and repairing the damaged vascular endothelium would be a critical step for treatment of cardiovascular diseases and stroke and acute organ injury. Using expression profiling and bioinformatics, we recently identified an adipocyte-enriched protein, adiporedoxin, as a negative regulator of endothelial activation (Sci Rep, 2016). In addition, we have identified a TRIM protein as a novel determinant of vascular endothelial inflammation via targeting VCAM-1 degradation. Currently, we are studying the roles and mechanisms of these proteins in vascular inflammation, atherosclerosis, sepsis and cerebral small vascular disease.
(selected from 90 peer-reviewed papers)
Liang J, Wang J, Azfer A, Song W, Tromp G, Kolattukudy PE, Fu M#. A novel CCCH-Zinc finger protein family regulates proinflammatory activation of macrophages. J Biol Chem. 2008, 283:6337-6346.
Liang J, Lei T, Song Y, Yanes N and Fu M#. RNA-destabilizing factor Tristetraprolin negatively regulates NF-κB signaling. J Biol Chem. 2009, 284: 29383-29390.
Liang J, Saad Y, Lei T, Wang J, Qi D, Yang Q, Kolattukudy PE and Fu M#. MCP-induced protein 1 deubiquitinating TRAFs and negatively regulate JNK and NF-κB signaling. J Exp Med, 2010, 207:2959-73.
Qi D, Huang S, Miao R, She ZG, Quinn T, Chang Y, Liu J, Fan D, Chen YE, Fu M#. Monocyte chemotactic protein-induced protein 1 (MCPIP1) suppresses stress granule formation and determines apoptosis under stress. J Biol Chem. 2011, 286(48):41692-700.
Zhang Y, Breevoort SR, Angdisen J, Fu M, Schmidt DR, Holmstrom AR, Kliewer SA, Mangelsdorf DJ, Schulman IG. Liver LXRα expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in mice. J Clin Invest, 2012, 122(5):1688-99.
Zhang J, Zhang Y, Sun T, Chandalia M, Abate N, Fan D, Xin HB, Chen YE# and Fu M#. Dietary obesity induced Egr-1 in adipocytes facilitates energy storage via suppression of FOXC2. Sci Rep. 2013, 3:1476.
Niu J, Shi Y, Xue J, Xu M, Miao R, Huang S, Chen ZJ, Fu M, Wu Z-H. DNA damage-induced MCPIP1 negatively regulates NF-κB activation by facilitating USP10-dependent disassembly of linear polyubiquitin chain. EMBO J, 2013, 32:3206-3219.
Liu S, Qiu C, Miao R, Zhou J, Fu W, Zhu L, Zhang L, Xu J, Fan D, Li K, Fu M#, Wang T#. MCPIP1 restricts HIV infection and is rapidly degraded in activated CD4+ T cells. Proc Natl Acad Sci U S A., 2013, 110(47):19083-8.
Yao H, Ma R, Yang L, Hu G, Chen X, Duan M, Kook Y, Niu F, Liao K, Fu M, Hu G, Kolattukudy P, Buch S. MiR-9 promotes microglial activation by targeting MCPIP1. Nat Commun. 2014. 5:4386.
Jeltsch KM, Hu D, Brenner S, Zöller J, Heinz GA, Nagel D, Vogel KU, Rehage N, Warth SC, Edelmann SL, Gloury R, Martin N, Lohs C, Lech M, Stehklein JE, Geerlof A, Kremmer E, Weber A, Anders HJ, Schmitz I, Schmidt-Supprian M, Fu M, Holtmann H, Krappmann D, Ruland J, Kallies A, Heikenwalder M & Heissmeyer V. Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation. Nat Immunol. 2014, 15(11):1079-1089.
Huang S, Liu S, Fu JJ, Tony Wang T, Yao X, Kumar A, Liu G, Fu M#. Monocyte Chemotactic Protein-induced Protein 1 and 4 Form a Complex but Act Independently in Regulation of Interleukin-6 mRNA Degradation. J Biol Chem. 2015 Aug 21;290(34):20782-92.
Guo F, He H, Fu ZC, Huang S, Chen T, Papasian CJ, Morse LR, Xu Y, Battaglino RA, Yang XF, Jiang Z, Xin HB, Fu M#. Adipocyte-derived PAMM suppresses macrophage inflammation by inhibiting MAPK signaling. Biochem J. 2015 Oct 5. pii:BJ20150019.
Lu W, Ning H, Gu L, Peng H, Wang Q, Hou R, Fu M, Hoft DF, Liu J. MCPIP1 Selectively Destabilizes Transcripts Associated with an Antiapoptotic Gene Expression Program in Breast Cancer Cells That Can Elicit Complete Tumor Regression. Cancer Res. 2016 Mar 15;76(6):1429-40.
He H, Guo F, Li Y, Saaoud F, Kimmis BD, Sandhu J, Fan M, Maulik D, Lessner S, Papasian CJ, Fan D, Jiang Z, Fu M#. Adiporedoxin suppresses endothelial activation via inhibiting MAPK and NF-κB signaling. Sci Rep. 2016 Dec 12;6:38975.
Cao L, Fu M, Kumar S, Kumar A. Methamphetamine potentiates HIV-1 gp120-mediated autophagy via Beclin-1 and Atg5/7 as a pro-survival response in astrocytes. Cell Death Dis. 2016 Oct 20;7(10):e2425.
Jiang MX, Hong X, Liao BB, Shi SZ, Lai XF, Zheng HY, Xie L, Wang Y, Wang XL, Xin HB, Fu M#, Deng KY#. Expression profiling of TRIM protein family in THP1-derived macrophages following TLR stimulation. Sci Rep. 2017 Feb 17;7:42781.
Fu M#, Blackshear PJ. RNA-binding proteins in immune regulation: a focus on CCCH zinc finger proteins. Nat Rev Immunol. 2017 Feb;17(2):130-143.
Li Y, Huang X, Huang S, He H, Lei T, Saaoud F, Yu XQ, Melnick A, Kumar A, Papasian CJ, Fan D, Fu M#. Central role of myeloid MCPIP1 in protecting against LPS-induced inflammation and lung injury. Signal Transduct Target Ther. 2017 Dec 8;2:17066
Prashek J, Bouyain S, Fu M, Li Y, Berkes D, Yao X. Interaction between the PH and START domains of ceramide transfer protein competes with phosphatidylinositol 4-phosphate binding by the PH domain. J Biol Chem. 2017 Aug 25;292(34):14217-14228.
Qian Y, Li X, Miao R, Liu S, Xin HB, Huang X, Wang TT, Fu M#. Selective degradation of plasmid-derived mRNAs by MCPIP1 RNase. Biochem J. 2019 Oct 15;476(19):2927-2938.
Lichawska-Cieslar A, Konieczny P, Szukala W, Declercq W, Fu M, Jura J. Loss of keratinocyte Mcpip1 abruptly activates the IL-23/Th17 and Stat3 pathways in skin inflammation. Biochim Biophys Acta Mol Cell Res. 2020 Sep 29;1868(1):118866.
Peng H, Ning H, Wang Q, Lai J, Wei L, Stumpo DJ, Blackshear PJ, Fu M, Hou R, Hoft DF, Liu J. Tristetraprolin Regulates TH17 Cell Function and Ameliorates DSS-Induced Colitis in Mice. Front Immunol. 2020 Aug 14;11:1952.
Zhou Z, Li X, Qian Y, Liu C, Huang X, Fu M#. Heat shock protein 90 inhibitors suppress pyroptosis in THP-1 cells. Biochem J. 2020 Oct 30;477(20):3923-3934.
Li Y, Huang X, Guo F, Lei T, Li S, Monaghan-Nichols P, Jiang Z, Xin HB, Fu M#. TRIM65 E3 ligase targets VCAM-1 degradation to limit LPS-induced lung inflammation. J Mol Cell Biol. 2020 Apr 24;12(3):190-201.
Huang X, Li Y, Li X, Fan D, Xin HB, Fu M#. TRIM14 promotes endothelial activation via activating NF-κB signaling pathway. J Mol Cell Biol. 2020 Apr 24;12(3):176-189.