Veronique Angeli

Ph.D
Associate Professor, Department of Microbiology
Principal Investigator, Immunology Programme
28 Medical Drive, Centre for Life Sciences, Level 3,
Singapore 117456
Tel: 6516 7207
Email: micva@nus.edu.sg

                      

Major Research Interests

Lymphatic vessel biology and function

Increasing evidence in the literature the function of lymphatic vessel is not limited to support the transport of immune cells and fluid but it is also critical for the transport of lipids and particularly cholesterol. Indeed, we found that in absence of functional lymphatic vessels, cholesterol transport from peripheral tissues back to the liver and bile is significantly impaired, and as a consequence, cholesterol accumulates in peripheral tissues. More importantly, we showed that this lymphatic transport of cholesterol is mediated by the transporter scavenger receptor class B type I on lymphatic endothelial cells which challenges the current view of lymphatic endothelium as a passive barrier. We are now investigating the clinical relevance of our findings particularly in atherosclerosis, a chronic inflammatory disease of large arteries resulting in part from the accumulation of cholesterol.

Macrophage biology and function

In addition to their immune functions, macrophages, being integral components of the tissues in which they reside, also contribute to local homeostatic functions. These trophic functions of macrophages are highly dependent on the tissue and on changes in their environment to which they respond rapidly. By contrast, virtually nothing is known about the function of perivascular macrophages in healthy blood vessels. We have evidence that perivascular macrophages are critical for maintaining large arteries functional homeostasis in mice as severe depletion of macrophages in healthy aorta leads to ECM remodelling particularly increased collagen, vessel stiffness and contractility dysfunction. Further phenotypic analysis of macrophage populations in aorta revealed that macrophages expressing lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1) represent the major resident macrophage subset of the vessel wall’s outer adventitial layer. Comparative gene-expression analysis and functional assays in vitro suggest that these LYVE-1+ macrophages are responsible for the maintenance of aorta integrity through their action on smooth muscle cells and modulation of collagen expression. These findings unveil an essential role of perivascular macrophages in maintaining vascular tone and identify these cells as a putative target for vascular diseases. The contribution of LYVE-1+ macrophage in arterial diseases and the origin of these macrophages are currently under investigations.

Recent Publications

Wang JK, Yeo KP, Chun YY, Tan TTY, Tan NS, Angeli V, Choong C (2017) Fish scale-derived collagen patch promotes growth of blood and lymphatic vessels in vivo. Acta Biomater: S1742-7061(17): 30564-0 (In press)

Trigueros-Motos L, van Capelleveen JC, Torta F, Castaño D, Zhang LH, Chai C, Kang M, Dimova LG, Schimmel AWM, Tietjen I, Radomski C, Tan LJ, Hwee TC, Narayanaswamy P, Wu D, Dorninger F, Yakala GK, Barhdadi A, Angeli V, Dubé MP, Berger J, Dallinga-Thie GM, Tietge UJF, Wenk MR, Hayden MR, Hovingh GK, Singaraja RR (2017) ABCA8 Regulates Cholesterol Efflux and High-Density Lipoprotein Cholesterol Levels. Arterioscler Thromb Vasc Biol 37(10)

Yeo KP, Angeli V (2017) Bidirectional crosstalk between lymphatic endothelial cell and T cell and its implications in tumor immunity. Frontiers in Immunol 8: 83

Goh, CC, Li JL, Becker D, Weninger W, Angeli V, Ng LG (2016) Inducing ischemia-reperfusion injury in the mouse ear skin for intravital multiphoton imaging of immune responses. J. Vis. Exp. 2016(118): e54956

Soh SY, Faveeuw C, Thiam CH, Khoo LH, Yeo KP, Lim SY, Lim HY, Ng JX, Angeli V (2016) NKT cell hyporesponsiveness leads to unrestrained accumulation of marginal zone B cells in Hypercholesterolemic Apolipoprotein E-deficient mice. J Immunol 197(10): 3894-3904

Liu X, Baarsma HA, Thiam CH, Montrone C, Brauner B, Fobo G, Heier JS, Duscha S, Königshoff M, Angeli V, Ruepp A, Campillos M (2016) Systematic identification of pharmacological targets from small-molecule phenotypic screens. Cell Chem Biol 23(10): 1302-13

Chua YL, Liong KH, Huang CH, Wong HS, Zhou Q, Ler SS, Tang Y, Low CP, Koh HY, Kuo IC, Zhang Y, Wong WS, Peh HY, Lim HY, Ge MQ, Haczku A, Angeli V, MacAry PA, Chua KY, Kemeny DM (2016) Blomia tropicalis-specific TCR transgenic Th2 cells induce inducible BALT and severe asthma in mice by an IL-4/IL-13-dependent mechanism. J Immunol 197(10): 3771-81

Kumar S, Chen M, Li Y, Wong FH, Thiam CW, Hossain MZ, Poh KK, Hirohata S, Ogawa H, Angeli V, Ge R (2016) Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque stability in ApoE(-/-) mice. Sci Rep 6: 31130

Li JL, Lim CH, Tay FW, Goh CC, Devi S, Malleret B, Lee B, Bakocevic N, Chong SZ, Evrard M, Tanizaki H, Lim HY, Russell B, Renia L, Zolezzi F, Poidinger M, Angeli V, St John AL, Harris JE, Tey HL, Tan SM, Kabashima K, Weninger W, Larbi A, Ng LG (2016) Neutrophils self-regulate immune complex-mediated cutaneous inflammation through CXCL2. J Invest Dermatol 136(2): 416-24

Pin YK, Khoo K, Tham M, Karwai T, Hwee TC, Puaux AL, Phua ML, Kato M, Angeli V, Abastado JP (2015) Lymphadenectomy promotes tumor growth and cancer cell dissemination in the spontaneous RET mouse model of human uveal melanoma. Oncotarget