Research
Li group is studying the basic mechanism of microtubule dysfunction in the pathogenesis of inflammatory disease, particularly inflammatory cardiovascular disease. Li’s research group revealed the regulatory machinery of microtubule function in inflammasome activation and in cardiovascular diseases. Li’s group currently focuses on deciphering the basic microtubule-dependent cellular and molecular mechanisms intertwined with innate immune response, and how the relevant regulation contributes to the development of inflammatory cardiovascular disease. Li group established and optimized a set of multidisciplinary approaches to analyse microtubule function in cardiovascular cells, particularly with a current focus on cardiomyocytes.
The heart is an exquisite machine. Cardiomyocyte is a fascinating cell type with many unresolved biology and pathology. It emerges that intracellular microtubule provides essential mechanical force in controlling cardiomyocyte contractility, and dysfunctional regulation of this machinery contributes to heart failure. Our efforts are to understand the basic microtubule biology in cardiovascular cells, to untangle the regulatory machinery in controlling microtubule function under pathology, and to accelerate the translation of our relevant basic research findings into the clinics.
Publications
- Baldrighi M, Doreth C, Li Y, Zhao X, Warner EF, Chenoweth H, Kishore K, Umrania Y, Minde DP, Winkler S,Yu X, Lu Y, Knapton A, Harrison J, Clarke MC, Latz E, de Cárcer G, Malumbres M, Ryffel B, Bryant CE, Liu J, Lilley KS, Mallat Z, Li X* (2023). PLK1 inhibition dampens NLRP3 inflammasome-elicited response in inflammatory disease models. J Clin Invest. 133(21):e162129. This work is featured as JCI cover research article for the 1st-Nov. 2023 issue.
- Warner E, Li Y, Li X* (2022). Targeting microtubules for the treatment of heart disease. Circulation Research. 130(11):1723-1741. *Invited author and Corresponding author.
- Yu X, Chen X, Amrute-Nayak M, Allgeyer E, Zhao A, Chenoweth H, Clement M, Harrision J, Doreth C, Sirinakis G, Krieg T, Zhou H, Huang H, Tokuraku K, St Johnston D, Mallat Z, Li X* (2021). MARK4 controls ischaemic heart failure through microtubule detyrosination. Nature 594, 560-565. *Corresponding author. Altmetric impact is 855. This article is in the 99th percentile (ranked 662nd) of the 345,376 tracked articles of a similar age in all journals and the 92nd percentile (ranked 68th) of the 893 tracked articles of a similar age in Nature. This work is one of BHF research highlights of 2021.
- Lu Y, Basatemur G, Scott IC, Chiarugi D, Clement M, Harrison J, Jugdaohsingh R, Yu X, Newland SA, Jolin HE, Li X, Chen X, Szymanska M, Haraldsen G, Palmer G, Fallon PG, Cohen ES, McKenzie ANJ, Mallat Z (2020). Interleukin-33 Signaling Controls the Development of Iron-Recycling Macrophages. Immunity. 52(5):782-793.e5.
- Clement M, Chen X, Chenoweth HL, Teng Z, Thome S, Newland SA, Harrison J, Yu X, Finigan AJ, Mallat Z, Li X* (2019). MARK4 (Microtubule Affinity-Regulating Kinase 4)-Dependent Inflammasome Activation Promotes Atherosclerosis. Arterioscler Thromb Vasc Biol. 39(8):1645-1651. *Corresponding author. Covered by the ATVB Journal front editorial “Enigma of inflammasome activation by kinases”.
- Baldrighi M, Mallat Z, Li X* (2017). NLRP3 inflammasome pathways in atherosclerosis. Atherosclerosis. 267:127-138. *Corresponding author.
- Li X*, Thome S, Ma XD, Amrute-Nayak M, Finigan A, Kitt L, Masters L, James, JR, Shi YG, Meng GY, Mallat Z (2017). MARK4 regulates NLRP3 positioning and inflammasome activation through a microtubule-dependent mechanism. Nature Communications. 28;8:15986. *Corresponding author.
- Li X, Deroide N, Mallat Z (2014). The role of the inflammasome in cardiovascular diseases. J Mol Med. 92(4): 307-19.
- Li X, Deroide N, Mallat Z (2014). MFG-E8 in the vascular System. Book chapter of “MFG-E8 and inflammation”: 85-95
- Deroide N, Li X* Lerouet D, Van Vré E, Baker L, Harrison J, Poittevin M, Masters L, Nih L, Margaill I, Iwakura Y, Ryffel B, Pocard M, Tedgui A, Kubis N, Mallat Z (2013). MFGE8 inhibits inflammasome-induced IL-1β production and limits postischemic cerebral injury. J Clin Invest. 123(3):1176-81. *Co-first author.
- Sanghavi P, Laxani S, Li X, Bullock S, Gonsalvez G. Dynein associates with oskar mRNPs and is requied for their efficient net plus-end localization in Drosophila oocytes (2013). PloS One. 8(11): e80605.
- Li X*, Kuromi H, Brigg L, Green DB, Rocha J, Sweeney S, Bullock SL (2010) BicD binds clathrin heavy chain to promote its transport and augments synaptic vesicle recycling. EMBO Journal. 29(5): 992-1006. Covered by the EMBO Journal front headline article “The more, the better: the BICD family gets bigger”.
- Dienstbier M, Li X* (2009) BicD and its role in cargo sorting by microtubule-based motors. Biochem Soc. Trans. 37(Pt 5): 1066-1071. *Invited author, Co-first author and Corresponding author.
- Dienstbier M, Boehl F, Li X, Bullock SL (2009) Egalitarian is a selective RNA-binding protein linking mRNA localization signals to the dynein motor. Genes & Development. 23 (13): 1546-1558.
- Li X, Brunton V, Burgar H, Wheldon L, Heath JK (2004) FRS2-dependent Src activation is required for FGFR-induced phosphorylation of Sprouty and suppression of ERK activity. J Cell Sci. 117:6007-6017.
- Tang Z, Zhao Y, Mei F, Yang S, Li X, Lv J, Hou L, Zhang B (2004) Molecular cloning and characterization of a human gene involved in transcriptional regulation of hTERT. Biochem Biophys Res Commun. 324:1324-1332.
- Wang Q, Bai Z, Li X, Hou L, Zhang B (2004) The evidence of human Orphan Receptor COUP-TFII inhibiting telomerase activity through decreasing hTERT transcription. Cancer Lett. 214:81-90.
- Li X*, Wheldon L, Heath JK (2003) Sprouty: a controversial role in receptor tyrosine kinase signalling pathways. Biochem Soc. Trans. 31: 1445-1446. * Invited author, First author and Corresponding author.
