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Jeremie Boucher
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Jeremie Boucher Group

Research group
Pågående forskning
Project owner
University of Gothenburg

Short description

Jeremie Boucher, PhD, Adjunct Senior Lecturer (Associate Professor) in Molecular Medicine.

About Jeremie Boucher Group

Jeremie Boucher, PhD, Adjunct Senior Lecturer (Associate Professor), aims to identify novel targets and pathways for the treatment of obesity and type 2 diabetes. He is also employed as a Principal Scientist at AstraZeneca, where he is coordinating and driving the early discovery programs for the treatment of metabolic diseases. This constitutes a unique opportunity to quickly translate the research findings of his lab into potential medicine to improve patients’ life.

Adipose tissue plays a central role in the development of insulin resistance and diabetes. The Boucher lab is working on modulating adipose tissue phenotype for the treatment of metabolic diseases:

  1. Increasing brown adipose tissue abundance or activity or converting white into brown adipocytes holds promise for the treatment of metabolic diseases. We are characterizing the molecular pathways controlling the development, differentiation and function of white, beige and brown adipose cells, and the role that BMPs and the transcription factors PPARa and g play in those processes
  2. Senescence (aging of cells) of adipose tissue is closely associated with common cardiometabolic complications including type 2 diabetes and cardiovascular diseases. We are investigating the key drivers of senescence in the different adipose tissue cells (endothelial cells, mesenchymal stem cells, adipocytes) in metabolic diseases, how senescent cells communicate with other cells and tissues to impact metabolism, and how to inhibit senescence in adipose

International Collaborations

Jeremie Boucher has an extensive national and international collaboration network with researchers from Harvard Medical School, University of Pennsylvania, University of Virginia, University of Campinas, INSERM, the Novo Nordisk Foundation Center for Basic Metabolic Research, and the Integrated Cardio Metabolic Centre/Karolinska Institute

Jeremie Boucher

Contact Information

Jeremie Boucher

jeremie.boucher@gu.se
Jeremie.Boucher@astrazeneca.com

Visiting addresses:
The Lundberg Laboratory for Diabetes Research
Blå Stråket 5,
Sahlgrenska University Hospital,
SE-413 45 Göteborg

Astrazeneca
Pepparedsleden 1,
SE-431 50 Mölndal

Research Summary

Adipose tissue plays a central role in the development of insulin resistance and diabetes. Increasing fatty acid storage and utilization in adipose tissues in order to limit ectopic lipid accumulation into non adipose tissues, is essential to restore insulin sensitivity and treat type 2 diabetes. Mammals have two major types of adipose tissues, white and brown. White fat is essential for fatty acid storage, while brown fat is an essential component of non-shivering thermogenesis, and has the ability to utilize fatty acid and generate heat due to the unique presence of the protein UCP1. Under certain circumstances such as chronic cold exposure, white adipocytes can be converted into brown-like fat cells or beige cells with high oxidative and energy wasting capacity, a process called browning of white fat.

In humans, brown fat is inversely correlated with body mass index, and its activation is associated with metabolic improvements. In animal models, brown adipose tissue deficiency is associated with obesity and diabetes while increasing brown fat or browning of white fat has protective effects. Thus, activating brown fat or inducing browning of white adipose tissue has attractive potential for the treatment of obesity and diabetes.

Our lab investigates the molecular pathways that control the development, differentiation and function of white and beige/brown adipose cells. The ligand-gated transcription factor PPARg has been shown to play a major role in these processes. We have identified novel PPARg modulator small molecules that can convert human white adipocytes into UCP1-expressing brown-like adipocytes. Our lab aims at identifying the molecular mechanisms responsible for the white-to-brown adipocyte phenotypic switch, as well as identifying novel factors essential for brown adipocyte development and function. We are also investigating the roles that Bone Morphogenetic Proteins (BMPs) and the transcription factors PPARa play in those processes.

Senescence (aging of cells) is another area of research focus. Senescence of adipose tissue cells is closely associated with common cardiometabolic complications including type 2 diabetes and cardio-vascular disease. We are investigating the key drivers of senescence in the different adipose tissue cells (endothelial cells, mesenchymal stem cells, adipocytes) in metabolic diseases, how senescent cells communicate with other cells and tissues to impact metabolism, and how to inhibit senescence in adipose tissue.

Key Publications

2020

S. Maurer, M.Harms, J. Boucher. The colorful versatility of adipocytes: white-to-brown transdifferentiation and its therapeutic potential in man. FEBS Journal, in press; https://doi.org/10.1111/febs.15470; 2020

T. Kroon, M. Harms, S. Maurer, L. Bonnet, I. Alexandersson, A. Lindblom, A. Ahnmark, D. Nilsson, P. Gennemark, G. O’Mahony, V. Osinski, C. McNamara, J. Boucher. PPARa and PPARg synergize to induce robust browning of white fat in vivo. Mol. Metab. 36:100964 ; 2020

I. Alexandersson, M.J. Harms, J. Boucher. Isolation and culture of human mature adipocytes using Membrane mature Adipocyte Aggregate Cultures. J. Vis. Exp., 156 ; 2020

J. M. Hoffmann, J. R Grünberg, A. Hammarstedt, T. Kroon, T. U. Greiner, S. Maurer, I. Elias, V. Palsdottir, F. Bosch, J. Boucher, S. Hedjazifar, U. Smith. BMP4 gene therapy enhances insulin sensitivity but not adipose tissue browning in obese mice. Mol. Metab. 32, 15-26; 2020

S. Hedjazifar, R.K. Shahidi, A. Hammarstedt, L. Bonnet, C. Church, J. Boucher, M. Blüher, U. Smith. The Novel Adipokine Gremlin 1 Antagonizes Insulin Action and is Increased in Type 2 Diabetes and NAFLD/NASH. Diabetes, 69(3), 331-341; 2020

2019

M. J. Harms, Q. Li, S. Lee, C. Zhang, B. Kull, S. Hallen, A. Thorell, I. Alexandersson, C.E. Hagberg, X. Peng, A. Mardinoglu, K. Spalding, J. Boucher. Mature human white adipocytes cultured under membranes maintain identity, function, and can transdifferentiate into brown-like adipocytes. Cell Reports 27: 213-225, 2019

C. Morgantini, J. Jager, X. Li, L. Levi, V. Azzimato, A. Sulen, E. Barreby, C. Xu, M. Tencerova, E. Näslund, C. Kumar, F. Verdeguer, S. Straniero, K. Hultenby, N. K. Björkström, E. Ellis, M. Rydén, C. Kutter, T. Hurrey, V. Lauschke, J. Boucher, A. Tomčala, G. Krejčová, A. Bajgar, M. Aouadi. Liver macrophages regulate systemic metabolism through non-inflammatory factors. Nature Metabolism, 1: 445–459, 2019

2018

Carolina E. Hagberg,,Qian Li, Maria Kutschke, Debajit Bhowmick, Endre Kiss, Irina G. Shabalina, Matthew J. Harms, Olga Shilkova, Viviana Kozina, Jan Nedergaard, Jeremie Boucher, Anders Thorell, and Kirsty L. Spalding. Flow Cytometry of Mouse and Human Adipocytes for the Analysis of Browning and Cellular Heterogeneity. Cell Reports 2018 Sep 4; 24(10):2746-2756 | PubMed

2017

Cai W, Sakaguchi M, Kleinridders A, Gonzalez-Del Pino G, Dreyfuss JM, O'Neill BT, Ramirez AK, Pan H, Winnay JN, Boucher J, Eck MJ, Kahn CR. Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression. Nat Commun. 2017 Mar 27;8:14892

2016

Boucher J* , Softic S*, El Ouaamari A, Krumpoch MT, Kleinridders A, Kulkarni RN, O'Neill BT, Kahn CR. Differential Roles of Insulin and IGF-1 Receptors in Adipose Tissue Development and Function. Diabetes. 2016 Aug;65(8):2201-13

Softic S*, Boucher J*, Solheim MH, Fujisaka S, Haering MF, Homan EP, Winnay J, Perez-Atayde AR, Kahn CR. Lipodystrophy Due to Adipose Tissue-Specific Insulin Receptor Knockout Results in Progressive NAFLD. Diabetes. 2016 Aug;65(8):2187-200

El Ouaamari A, Dirice E, Gedeon N, Hu J, Zhou JY, Shirakawa J, Hou L, Goodman J, Karampelias C, Qiang G, Boucher J, Martinez R, Gritsenko MA, De Jesus DF, Kahraman S, Bhatt S, Smith RD, Beer HD, Jungtrakoon P, Gong Y, Goldfine AB, Liew CW, Doria A, Andersson O, Qian WJ, Remold-O'Donnell E, Kulkarni RN. SerpinB1 Promotes Pancreatic β Cell Proliferation. Cell Metab. 2016 Jan 12;23(1):194-205

2014

Boucher J , Charalambous M, Zarse K, Mori MA, Kleinridders A, Ristow M, Ferguson-Smith AC, Kahn CR. Insulin and insulin-like growth factor 1 receptors are required for normal expression of imprinted genes. Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):14512-7

Ussar S, Lee KY, Dankel SN, Boucher J, Haering MF, Kleinridders A, Thomou T, Xue R, Macotela Y, Cypess AM, Tseng YH, Mellgren G, Kahn CR. ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes. Sci Transl Med. 2014 Jul 30;6(247):247ra103

Mori MA, Thomou T, Boucher J, Lee KY, Lallukka S, Kim JK, Torriani M, Yki-Järvinen H, Grinspoon SK, Cypess AM, Kahn CR. Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy. J Clin Invest. 2014 Aug;124(8):3339-51

Boucher J , Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states.

Cold Spring Harb Perspect Biol. 2014 Jan 1;6(1). pii: a009191. Review.

2013

Bagchi M, Kim LA, Boucher J, Walshe TE, Kahn CR, D'Amore PA. Vascular endothelial growth factor is important for brown adipose tissue development and maintenance. FASEB J. 2013 Aug;27(8):3257-71

Liew CW*, Boucher J*, Cheong JK, Vernochet C, Koh HJ, Mallol C, Townsend K, Langin D, Kawamori D, Hu J, Tseng YH, Hellerstein MK, Farmer SR, Goodyear L, Doria A, Blüher M, Hsu SI, Kulkarni RN. Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance. Nat Med. 2013 Feb;19(2):217-26

2012

Vernochet C, Mourier A, Bezy O, Macotela Y, Boucher J, Rardin MJ, An D, Lee KY, Ilkayeva OR, Zingaretti CM, Emanuelli B, Smyth G, Cinti S, Newgard CB, Gibson BW, Larsson NG, Kahn CR. Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance. Cell Metab. 2012 Dec 5;16(6):765-76

Boucher J , Mori MA, Lee KY, Smyth G, Liew CW, Macotela Y, Rourk M, Bluher M, Russell SJ, Kahn CR.

Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling. Nat Commun. 2012 Jun 12;3:902

2010

Boucher J , Macotela Y, Bezy O, Mori MA, Kriauciunas K, Kahn CR. A kinase-independent role for unoccupied insulin and IGF-1 receptors in the control of apoptosis. Sci Signal. 2010 Dec 7;3(151):ra87

Winnay JN, Boucher J, Mori MA, Ueki K, Kahn CR. A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response. Nat Med. 2010 Apr;16(4):438-45

2008

Dray C, Knauf C, Daviaud D, Waget A, Boucher J, Buléon M, Cani PD, Attané C, Guigné C, Carpéné C, Burcelin R, Castan-Laurell I, Valet P. Apelin stimulates glucose utilization in normal and obese insulin-resistant mice. Cell Metab. 2008 Nov;8(5):437-45

2005

Boucher J , Masri B, Daviaud D, Gesta S, Guigné C, Mazzucotelli A, Castan-Laurell I, Tack I, Knibiehler B, Carpéné C, Audigier Y, Saulnier-Blache JS, Valet P. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology. 2005 Apr;146(4):1764-71

Grants and Awards

  • 2020-2024: Swedish Foundation for Strategic Research (SSF)
  • 2019-2021: Post-doctoral fellowship, AstraZeneca
  • 2018-2020: Post-doctoral fellowship, AstraZeneca
  • 2017: Wallenberg Academy Fellowship of the Knut and Alice Wallenberg Foundation, Sweden
  • 2016-2018: Post-doctoral fellowship, AstraZeneca
  • 2015-2017: Post-doctoral fellowship, AstraZeneca
  • 2013: Adipose tissue biology Keystone Symposia scholarship
  • 2012: Endocrine society travel award
  • 2008: Endocrine society travel award
  • 2004: ATER fellowship (Temporary Assignment for Research and Teaching)
  • 2001-2003: MENRT fellowship from French Ministry of National Education, Research and Technology
  • 2000: M.Sc. fellowship from Ecole Doctorale Biologie Sante Biotechnologie, Toulouse

Group Members

Laurianne Bonnet

Post-doctoral fellow
Ph.D from Aix-Marseille University

Tobias Kroon

Post-doctoral fellow
Ph.D in Pharmacology, SLU, Uppsala, Sweden
M.Sc. in Pharmacy, University of Gothenburg, Sahlgrenska Academy, Sweden

Ida Alexandersson

Industrial PhD
M.Sc. in Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden

Alumni

 

Matthew Harms

Post-doctoral fellow, AstraZeneca
Ph.D in Cell and Molecular Biology, University of Pennsylvania, USA
B.S. in Physiology from the University of California Santa Barbara, USA

Stefanie Maurer

Post-doctoral fellow, AstraZeneca
Ph.D in Physiology, Technical University of Munich, Germany
M.Sc. in Nutritional Sciences, Technical University of Munich, Germany

Daniel Nilsson

Post-doctoral fellow
Ph.D from Sahlgrenska academy/University of Gothenburg
M.Sc. from Stanford DNA Sequencing and Technology Center, California, USA