Behmoaras Jacques Vincent

Associate Professor

Deputy Director

Email

Contact: 66011137

Education
2005 PhD in Molecular and Cellular Biology, University Paris V René Descartes, France
2001 MSc in Biology of Ageing, University Paris V René Descartes, France
2000 BSc in Biochemistry, University Paris VII Denis Diderot, France

Professional experience
I have obtained my PhD in 2005 in University of Paris where I got familiarized with quantitative genetics in vascular biology. After a postdoc at Imperial College London, (2005-2009), I setup my research programme, focusing on system-level understanding of macrophage biology in inflammatory disease, including chronic kidney disease and metabolic syndrome. To do so, I obtained the Imperial College Junior Research Fellowship (2009), followed by tenured academic positions (Lecturer, Senior lecturer, Reader in Immunogenetics) as well as >1.5 M extramural funding as a principal investigator in the Department of Immunology and Inflammation, Imperial College London. In 2021, I joined Duke-NUS Medical School as an Associate Professor and Deputy Director, Centre for Computational Biology, Program in Cardiovascular and Metabolic Disorders.
My main interest is to understand and target gene networks that controls macrophage function in complex inflammatory disorders. We use patient populations as well as animal models of chronic kidney disease, wound healing/fibrosis, metabolic syndrome and bone inflammation. We apply systems-genetics approaches to target macrophage activity. Our recent approaches pointed towards the importance of targeting macrophage energy metabolism, mitochondrial function and ion control in inflammatory and metabolic disease (Nature Communications 2017, Mol Metab 2018, Cell Reports 2019, Elife 2020, Br J Pharmacol 2021).

Two key areas of research in my group include:

• Macrophage immunometabolism in chronic kidney disease: We showed that targeting branched chain amino acid catabolism and iron homeostasis affect macrophage mitochondrial function and reduce the severity of chronic kidney disease (Nature Comm 2017, Cell Reports 2019 and J. Cell. Sci. 2020). We currently aim to understand and target the evolution of macrophage polarization and its immunometabolism at single cell resolution in the renal microenvironment. 

• Metabolic Syndrome. When molecular drivers of healthy adipogenesis are perturbed, this can cause hepatic steatosis. We use animal models of obesity and ageing (Mol Metab 2018) and combine deep phenotyping of bariatric patient-derived white adipose tissue (WAT) with ex vivo treatment of WAT explants (Br J Pharmacol 2021), in order to target macrophage dynamics during dysfunctional adipogenesis. By using a comprehensive panel of WAT phenotypes, we are currently focusing on machine learning approaches that can predict hepatic insulin resistance.

Selected Recent Publications  (¶corresponding)

2021 Buang N, Tapeng L, Gray V, Sardini A, Whilding C, Lightstone L, Cairns TD, Pickering MC, Behmoaras J, Ling GS, Botto M. Type I interferons affect the metabolic fitness of CD8 + T cells from patients with systemic lupus erythematosus. Nat Commun 2021 Mar 31;12(1):1980.  doi: 10.1038/s41467-021-22312-y.

2021 Olona A, Hateley C, Guerrero A, Ko JH, Johnson MR, Anand PK, Thomas D, Gil J and Behmoaras J¶. Cardiac glycosides cause cytotoxicity in human macrophages and ameliorate white adipose tissue homeostasis. Br J Pharmacol. 2021 Mar 4. doi: 10.1111/bph.15423. Online ahead of print.

2020 Ko JH, Olona A, Papathanassiu AE, Buang N, Park KS, Costa ASH, Mauro C, Frezza C and Behmoaras J¶. BCAT1 affects mitochondrial metabolism independently of leucine transamination in activated human macrophages. J Cell Sci. 2020 Nov 27;133(22):jcs247957. doi: 10.1242/jcs.247957.

2020 Pereira M, Ko JH, Logan J, Protheroe H, Kim KB, Tan ALM, Croucher PI, Park KS, Rotival M, Petretto E, Bassett JD¶, Williams GR¶ and Behmoaras J¶. A trans-eQTL network regulates osteoclast multinucleation and bone mass. Elife. 2020 Jun 19;9:e55549. doi: 10.7554/eLife.55549

2019 Guerrero A, Herranz N, Sun B, Wagner V, Gallage S, Guiho R, Wolter K, Pombo J, Irvine E, Innes AJ, Birch J, Glegola J, Manshaei S, Heide D, Dharmalingam G, Harbig J, Olona A, Behmoaras J, Dauch D, Uren AG, Zender L, Vernia S, Martínez-Barbera JP, Heikenwalder M, Withers DJ and Gil J. Cardiac glycosides are broad-spectrum senolytics. Nature Metabolism, 2019 Nov;1(11):1074-1088.

2019 Pereira M, Chen TD, Buang N, Olona A, Ko JH, Prendecki M, Costa ASH, Nikitopoulou E, Tronci L, Pusey CD, Cook HT, McAdoo SP, Frezza C and Behmoaras J¶. Acute iron deprivation reprograms human macrophage metabolism and reduces inflammation in vivo. Cell Reports. 2019 Jul 9;28(2):498-511

2019 Bagnati M, Moreno-Moral A, Ko JH, Nicod J, Harmston N, Imprialou M, Game L, Gil J, Petretto E¶ and Behmoaras J¶. Systems genetics identifies a macrophage cholesterol network associated with physiological wound healing. JCI Insight. 2019 Jan 24;4(2)

2018 Srivastava PK, Eyll JV, Godard P, Mazzuferi M, Delahaye-Duriez A, Steenwinckel JV, Gressens P, Danis B, Vandenplas C, Foerch P, Leclercq K, Mairet-Coello G, Cardenas A, Vanclef F, Laaniste L, Niespodziany I, Keaney J, Gasser J, Gillet G, Shkura K, Chong SA, Behmoaras J, Kadiu I, Petretto E, Kaminski RM, Johnson MR. A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target. Nat Commun. 2018 Sep 3;9(1):3561

2018 Olona A, Terra X, Ko, JH, Grau-Bové C, Pinent M, Ardevol A, Garcia Diaz A, Moreno-Moral A, Edin, M, Bishop-Bailey D, Zeldin DC, Aitman TJ, Petretto E, Blay M and Behmoaras J¶. Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis. Mol Metab, 2018 May;11:18-32

2018 Moreno-Moral A, Bagnati B, Koturan S, Ko, JH, Fonseca C, Harmston N, Game L, Martin J, Ong V, Abraham DJ, Denton CP, Behmoaras J¶, Petretto E¶. Changes in macrophage transcriptome associate with systemic sclerosis and mediate GSDMA contribution to disease risk. Ann Rheum Dis, 2018 Apr;77(4):596-601.

2017 Papathanassiu A¶, Ko JH, Imprialou M, Bagnati M, Srivastava PK, Vu HA, Cucchi D, McAdoo SP, Ananieva EA, Mauro C¶ and Behmoaras J¶. BCAT1 controls metabolic reprogramming in activated human macrophages and is associated with inflammatory diseases. Nat Commun, 2017 Jul 12;8:16040.

2017 Chen TD, Rotival M, Chiu LY, Bagnati M, Ko JH, Srivastava PK, Petretto E, Pusey CD, Lai PC, Aitman TJ, Cook HT and Behmoaras J¶. Identification of Ceruloplasmin as a Gene that Affects Susceptibility to Glomerulonephritis Through Macrophage Function. Genetics. 2017 Jun;206(2):1139-1151

2017 Srivastava PK, Bagnati M, Delahaye-Duriez A, Ko JH, Rotival M, Langley SR, Shkura K, Mazzuferi M, Danis B, van Eyll J, Foerch P, Behmoaras J, Kaminski RM, Petretto E, Johnson MR. Genome-wide analysis of differential RNA editing in epilepsy. Genome Res. 2017 Mar;27(3):440-450.

2016 Martínez-Micaelo N, González-Abuín N, Terra X, Ardévol A, Pinent M, Petretto E, Behmoaras J¶, Blay M¶. Identification of a nutrient-sensing transcriptional network in monocytes by using inbred rat models on a cafeteria diet. Dis Model Mech. 2016 Oct 1;9(10):1231-1239.

2015 Behmoaras J¶, Diaz AG, Venda L, Ko JH, Srivastava P, Montoya A, Faull P, Webster Z, Moyon B, Pusey CD, Abraham DJ, Petretto E, Cook TH, Aitman TJ¶. Macrophage epoxygenase determines a profibrotic transcriptome signature. J Immunol. 2015 May 15;194(10):4705-4716.

2015 Johnson MR, Behmoaras J, Bottolo L, Krishnan ML, Pernhorst K, Santoscoy PL, Rossetti T, Speed D, Srivastava PK, Chadeau-Hyam M, Hajji N, Dabrowska A, Rotival M, Razzaghi B, Kovac S, Wanisch K, Grillo FW, Slaviero A, Langley SR, Shkura K, Roncon P, De T, Mattheisen M, Niehusmann P, O'Brien TJ, Petrovski S, von Lehe M, Hoffmann P, Eriksson J, Coffey AJ, Cichon S, Walker M, Simonato M, Danis B, Mazzuferi M, Foerch P, Schoch S, De Paola V, Kaminski RM, Cunliffe VT, Becker AJ and Petretto E. Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus. Nat Commun. 2015 Jan 23;6:6031.

2015 Rotival M, Ko JH, Srivastava PK, Kerloc'h A, Montoya A, Mauro C, Faull P, Cutillas PR, Petretto E¶ and Behmoaras J¶. Integrating phosphoproteome and transcriptome reveals new determinants of macrophage multinucleation. Mol Cell Proteomics. 2015 Mar;14(3):484-98.

2014 Kang H, Kerloc’h A, Rotival M, Xu X, Zhang Q, D’Souza Z, Kim M, Scholz JC, Ko JH, Srivastava PK, Genzen JR, Cui W, Aitman TJ, Game L, Melvin JE, Hanidu A, Dimock J, Zheng J, Souza D, Behera AK, Nabozny G, Cook HT, Bassett JHD, Williams GR, Li, J, Vignery A¶, Petretto E¶ and Behmoaras J¶. Kcnn4 is a regulator of macrophage multinucleation in bone homeostasis and inflammatory disease. Cell Reports, 2014 21;8(4):1210-24.