Dr Xuan Li

Dr Xuan Li

Principal Investigator, British Heart Foundation (BHF) Senior Basic Science Research Fellow

XL315@cam.ac.uk

Twitter: https://twitter.com/GroupXuan

LinkedIn: https://www.linkedin.com/in/xuan-li-20a8b0130/

External link: https://www.xuanlab.org

Biography 

Dr Xuan Li completed medical training in China and then had research training in biochemistry (CRUK PhD student at the University of Birmingham), microtubule cell biology (MRC Career Development Fellow at MRC-LMB, Cambridge) and cardiovascular medicine (University of Cambridge) in the UK before she established her own research group in Cambridge.

Li group is studying the basic mechanism of microtubule dysfunction in the pathogenesis of the inflammatory disease, particularly inflammatory cardiovascular disease. Li’s research group revealed the regulatory machinery of microtubule function in inflammasome activation and in cardiovascular diseases. Her 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.

Research Approach:

We use a set of multidisciplinary approaches to study microtubule dysfunction in cardiovascular diseases:

• Cardiovascular disease models & associated in vivo assessments

(Atherosclerosis; Myocardial infarction; Cardiomyopathy; Heart failure; Sepsis).

• Studies on clinical samples and clinical data.
• Primary cell isolation and culture (cardiomyocyte, Smooth muscle cell, Macrophage).
• Single cardiomyocyte physiology using IonOptix full calcium and contractility system.
• Cell phenotyping using advanced microscopy, flow cytometry, and ImageStream.
• Biochemistry, cell biology and biophysics of the microtubule cytoskeleton in cardiovascular cells (cardiomyocytes, smooth muscle cells, immune cells).
• Genetics and Bioinformatics

Current projects:

• To understand how microtubule dysfunction in cardiovascular cells contributes to cardiovascular disease development.
• To elucidate the interplay between inflammation and microtubule function in cardiovascular cells during the pathogenesis of cardiovascular diseases.
• To establish robust in vitro human cardiomyocyte culture to study microtubule function.
• To develop translational aspects of targeting relevant microtubule players to diagnose and treat cardiovascular diseases.

Selected Publications

1. 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. PLK1 inhibition dampens NLRP3 inflammasome-elicited response in inflammatory disease models. J Clin Invest. 2023. 133(21): e162129. The work is a featured cover research article.The work is highlighted as the editor’s pick in JCI This Month.

2. Warner E, Li Y, Li X. Targeting microtubules for the treatment of heart disease. Circulation Research. 2022. 130 (11):1723-1741.

3. 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. MARK4 controls ischaemic heart failure through microtubule detyrosination. Nature. 2021. 594, 560-565.  This work is one of BHF research highlights 2021.

4. Clement M, Chen X, Chenoweth HL, Teng Z, Thome S, Newland SA, Harrison J, Yu X, Finigan AJ, Mallat Z, Li X. MARK4 (Microtubule Affinity-Regulating Kinase 4)-Dependent Inflammasome Activation Promotes Atherosclerosis. Arterioscler Thromb Vasc Biol. 2019. 39(8):1645-1651. This work is covered by the ATVB Journal front editorial “Enigma of inflammasome activation by kinases”.

5. Li X*, Thome S, Ma XD, Amrute-Nayak M, Finigan A, Kitt L, Masters L, James, JR, Shi YG, Meng GY, Mallat Z. MARK4 regulates NLRP3 positioning and inflammasome activation through a microtubule-dependent mechanism. Nature Communications. 2017. 28;8:15986. *Corresponding author.