Name: Svetoslav Chakarov

Title：PI

Email: 184468@shsmu.edu.cn

Tel: 86-021-63846590-776796

Research Interests

Obesity, defined as excess fat mass, increases risks for multiple metabolic diseases, such as type 2 diabetes, cardiovascular disease and several types of cancer. The obesity epidemic has intensified efforts to understand the mechanisms controlling obesity-induced tissue remodeling. Adipose tissue associated macrophages (ATM) are hypothesized to play central roles in these diseases, through their role as inflammatory mediators. In addition to inflammation, a prototypical macrophage function, ATM perform ‘extra’ tissue-specific functions termed accessory functions. One such putative accessory function is their metabolic activity. However, the role of ATM metabolism in shaping tissue remodeling during obesity is poorly understood. In our study we propose to use a high dimensional flow cytometry-based proteomic screening combining metabolic activities, phenotype and epigenetic, called SCREEN3. This newly developed technic in our lab is easy to use and can be applied for human and mouse samples. In addition, the combination of SCREEN3 with human and mouse single cell RNA sequencing data will allow us to better understand ATM diversity in term of gene expression, phenotype, metabolism and epigenetic remodelling at steady state and during disease. Finally using Hyperion Imaging Mass Cytometry (IMC) we will validate and characterize the crosstalk between ATM and their adipose tissue microenvironment.

Ten Selected Papers

*co-corresponding authors; #co-first authors

1. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches.Chakarov S, Lim HY, Tan L, Lim SY, See P, Lum J, Zhang XM, Foo S, Nakamizo S, Duan K, Kong WT, Gentek R, Balachander A, Carbajo D, Bleriot C, Malleret B, Tam JKC, Baig S, Shabeer M, Toh SES, Schlitzer A, Larbi A, Marichal T, Malissen B, Chen J, Poidinger M, Kabashima K, Bajenoff M, Ng LG, Angeli V, Ginhoux F Science. 2019 Mar 15;363(6432). pii: eaau0964. doi: 10.1126/science.aau0964.

2. Determinants of resident tissue macrophage form and function. Bleriot C, Chakarov S, Ginhoux F, Immunity 2020 Jun 16 52, 957-970 doi: 10.1016/j.immuni.2020.05.014

3. Fate mapping via Ms4a3-expression history traces monocyte-derived cells. Liu Z, Gu Y, Chakarov S, Bleriot C, Kwok I, Chen X, Shin A, Huang W, Dress RJ, Dutertre CA, Schlitzer A, Chen J, Ng LG, Wang H, Liu Z, Su B, Ginhoux F Cell. 2019 Sep 5 178, 1509-1525 doi: 10.1016/j.cell.2019.08.009

4. Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung. Schyns J, Bai O, Ruscitti C, Radermecker C, De Schepper S, Chakarov S, Farnir F, Pirottin D, Ginhoux F, Boeckxstaens G, Bureau F, Marichal T Nat Commun. 2019 Sep 3; 10:3964 doi: 10.1038/s41467-019-11843-0

5. Hyaluronan receptor lyve-1-expressing macrophages maintain arterial tone through hyaluronan-mediated regulation of smooth muscle cell collagen. Lim HY, Lim SY, Tan CK, Thiam CH, Goh CC, Carbajo D, Chew SHS, See P, Chakarov S, Wang XN, Lim LH, Johnson LA, Lum J, Fong CY, Bongso A, Biswas A, Goh C, Evrard M, Yeo KP, Basu R, Wang JK, Tan Y, Jain R, Tikoo S, Choong C, Weninger W, Poidinger M, Stanley ER, Collin M, Tan NS, Ng LG, Jackson DG, Ginhoux F, Angeli V Immunity. 2018 Aug 21;49(2):326-341.e7. doi: 10.1016/j.immuni.2018.06.008.

6. Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinom Sharma A, Seow J, Dutertre CA, Pai R, Blériot C, Mishra A, Wong R, Singh G, Sudhagar S, Khalilnezhad S, Erdal S, Teo HM, Khalilnezhad A, Chakarov S, Kiat Hon Lim T, Chung Yaw Fui A, Kow Wei Chieh A, Cheow Peng Chung CP, Bonney G, Goh Kim Poh B, Chan J, Chow P, Ginhoux F, DasGupta R, Cell 2020 Oct 15 183, 1–18 doi: 10.1016/j.cell.2020.08.040

7. Exposure to bacterial CpG DNA protects from airway allergic inflammation by expanding regulatory lung interstitial macrophages. Sabatel C, Radermecker C, Fievez L, Paulissen G, Chakarov S, Fernandes C, Olivier S, Toussaint M, Pirottin D, Xiao X, Quatresooz P, Sirard JC, Cataldo D, Gillet L, Bouabe H, Desmet CJ, Ginhoux F, Marichal T, Bureau F Immunity. 2017 Mar 21;46(3):457-473. doi: 10.1016/j.immuni.2017.02.016.

8. Cell-autonomous FLT3L shedding via ADAM10 mediates conventional dendritic cell development in mouse spleen . Fujita K#, Chakarov S#, Kobayashi T, Sakamoto K, Voisin B, Duan K, Nakagawa T, Horiuchi K, Amagai M, Ginhoux F, Nagao K PNAS. 2019 Jul 16;116(29):14714-14723 doi: 10.1073/pnas.1818907116

9. Unsupervised high-dimensional analysis aligns dendritic cells across tissues and species. Guilliams M, Dutertre CA, Scott CL, McGovern N, Sichien D, Chakarov S, Van Gassen S, Chen J, Poidinger M, De Prijck S, Tavernier SJ, Low I, Irac SE, Mattar CN, Sumatoh HR, Low GHL, Chung TJK, Chan DKH, Tan KK, Hon TLK, Fossum E, Bogen B, Choolani M, Chan JKY, Larbi A, Luche H, Henri S, Saeys Y, Newell EW,   Lambrecht    BN,    Malissen   B,   Ginhoux    F   Immunity.    2016    Sep    20;45(3):669-684.    doi: 10.1016/j.immuni.2016.08.015. Epub 2016 Sep13.

10. Mpath maps multi-branching single-cell trajectories revealing progenitor cell progression during development. Chen J, Schlitzer A, Chakarov S, Ginhoux F, Poidinger M Nat Commun. 2016 Jun 30; 7:11988. doi: 10.1038/ncomms11988