Theme 3: Immunometabolic dialogue in obesity and its comorbidities
Dr David Dombrowicz
UMR1011. Inserm
European Genomic Institute for Diabetes
Université de Lille - CHU Lille
Institut Pasteur de Lille.
1, r. Prof. Calmette BP245
59019 Lille Cedex - France
Tel. + 33 320 87 79 67
Mobile. + 33 685 28 47 16
Fax. + 33 320 87 73 60
Summary biography :
David Dombrowicz, a biologist and botanist by training, received his Ph.D. in endocrinology in 1991 from the University of Liege (Belgium).
During his post-doctoral fellowship at the NIH, NIAID (Bethesda, MD) in the laboratory of Dr. Jean-Pierre Kinet, he performed the first inactivation of the alpha and beta subunits of the high-affinity IgE receptor FcepsilonRI and studied the role of this receptor as well as FcgammaRIII/CD16 in anaphylactic reactions. In 1996, he joined the Inserm Unit headed by Professor André Capron at the Pasteur Institute in Lille. As co-leader of the team, he studied with Professor Monique Capron the role of Fc receptors, in particular their expression and function on eosinophils and in allergic and inflammatory diseases (asthma, atopic dermatitis and colitis). He then studied the immunoregulatory properties of prostaglandin D2 and nuclear receptors, in particular peroxisome proliferator-activated receptors (PPAR).
Since 2005, he is a research director at Inserm. In 2010, he joined the Inserm Unit headed by Bart Staels, at the Pasteur Institute of Lille, to lead a team working on nuclear receptor immunoinflammation and immunometabolism.
D. Dombrowicz is the author of more than 90 papers and has an H-factor of 35.
Orcid. 0000-0002-0485-8923. Researcher ID. F-7044-2013.
Awards and honours:
In 2018. D. Dombrowicz received a Publons Award (Top 1% of reviewers for immunology) and in 2017 he was in the "Top 3" reviewers of the Journal of Allergy and Clinical Immunology.
In 1999, Dombrowicz received the Pharmacia Allergy Research Foundation Award and in 2013, the Ming K. Jeang Award for Excellence in Cell and Tissue Biology. Jeang Award for Excellence in Cell and Biosciences (article Kostadinova et al. Cell & Bioscience 2012, 2:34. (2013)
D. Dombrowicz is a regular member of international evaluation committees for NIH, EU (FP6, FP7, H2020, IMI)....
Keywords :
Inflammation, Immune cells, Nuclear receptors, Type 2 diabetes, Obesity, Atherosclerosis, NASH, NAFLD, Psoriasis, Atopic dermatitis, Allergic asthma
Research areas:
We are studying the contribution of immune cells to obesity and its complications (type 2 diabetes, atherosclerosis and NASH) with a focus on regulation by immuno-expressed nuclear receptors (FXR, RORalpha and Rev-erbalpha) and the impact of metabolism on immune cells and responses.
1. Although the expression of bile acid receptors in lymphoid cells has been identified by the team, their role is unknown. Using a mouse model of mapping the expression and inactivation of cell-specific genes, metabolic and immune phenotyping analyses and omics approaches, we are investigating the contribution of FXR and TGR5 expression by lymphocytes to the development of obesity and related pathologies.
2. RORalpha is a receptor for cholesterol and its derivatives with a wide cellular distribution in the immune system, while Rev-erb, a binding heme, has an antagonistic effect. Both receptors are involved in the control of circadian clocks. We are studying the impact of RORalpha expression in T-cell subpopulations and in myeloid cells as well as Rev-erbalpha expression in T-cells in metabolic diseases.
3. We have shown that fatty acids modulate the innate inflammatory response through metabolic reprogramming, the impact of other diet-related compounds on the innate and adaptive response will be studied. We have reported on the alteration of immune populations, particularly T cells, associated with the progression of NALFD from steatosis to NASH in patients and in preclinical models; we will further investigate how T cells interact with other immune populations, particularly innate lymphoid cells, and contribute to disease progression.
Competencies :
• Preclinical disease models: Type 2 diabetes, Obesity, Atherosclerosis, NASH, Food allergies, Colitis, Allergic asthma, Atopic dermatitis, Psoriasis, Contact hypersensitivity.
• Translational studies (collaborations with Prof. D. Staumont-Sallé, Department of Dermatology, University Hospital of Lille; Prof. F. Pattou, Inserm U1190 and Department of Metabolic Surgery, University Hospital of Lille and Prof. S. Francque, Department of Hepatology, AZ Antwerpen (Belgium).
• Cytometry : Flow cytometry, mass cytometry, cell sorting.
• Metabolic Immunophenotyping platform. www.egid.fr/plateformes/
• Invasive Plethysmography.
• Histology: Immunohistochemistry, Microdissection by laser capture.
• Intracellular metabolism: "Seahorse" oximetry.
• Genetically modified mice.
• Molecular biology: (RT-PCR, microarrays
- D.A. Mogilenko, J.T. Haas, L. Lhomme, S. Fleury, S. Quemener, M. Levavasseur, C. Becquart, J. Wartelle, A. Bogomolova, L. Pineau, O. Molendi-Coste, S. Lancel, H. Dehondt, C. Gheeraert, A. Melchior, C. Dewas, A. Nikitin, S. Pic, N. Rabhi, J.S. Annicotte, S. Oyadomari, T. Velasco-Hernandez, J. Cammenga, M. Foretz, B. Viollet, M. Vukovic, A. Villacreces, K. Kranc, P. Carmeliet, G. Marot, A. Boulter, S. Tavernier, L. Berod, M.P. Longhi, C. Paget, S. Janssens, D. Staumont-Salle, E. Aksoy, B. Staels, D. Dombrowicz. Metabolic and innate immune cues merge into a specific inflammatory response via the UPR. Cell, 2019, 177, 1201-1216 (with Editorial material)
- J.T. Haas, L. Vonghia, D.A.Mogilenko, A. Verrijken, O. Molendi-Coste, S. Fleury, A. Deprince, A. Nikitin, E. Woitrain, L. Ducrocq-Geoffroy, S. Pic, B. Derudas, H. Dehondt, C. Gheeraert, L. Van Gaal, A. Driessen, P. Lefebvre, B. Staels, S. Francque, D. Dombrowicz. Transcriptional network analysis implicates altered hepatic immune function in NASH development and resolution. Nat. Metab., 2019, 1, 604-614
- R. Paumelle, J.T. Haas, N. Hennuyer, E. Bauge, Y. Deleye, D. Mesotten, L. Langouche, J. Vanhoutte, C. Cudejko, K Wouters, S.A. Hannou, V. Legry, S. Lancel, F. Lalloyer, A. Polizzi, S. Smati, P. Gourdy, E. Vallez, E. Bouchaert, B. Derudas, H. Dehondt, C. Gheeraert, S. Fleury, A. Tailleux, A. Montagner, W. Wahli, G. Van Den Berghe, H. Guillou, D. Dombrowicz, B. Staels. Hepatic PPARα is critical in the metabolic adaptation to sepsis. J. Hepatol, 2019, 70, 963-973
- L. Everaere, S. Ait-Yahia, O. Molendi-Coste, H. Vorng, S. Quemener, P. Le Vu, S. Fleury, E. Bouchaert, Y. Fan, C. Duez, P. De Nadai, B. Staels, D. Dombrowicz*, A. Tsicopoulos. Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity. J. Allergy Clin. Immun., 2016, 138, 1309-1318 (with Editorial material) (*co-corresponding author)
- V. Julia, L. Macia, D. Dombrowicz. The impact of diet on asthma and allergic diseases. Nat. Rev. Immunol., 2015, 15, 308-322
Contact for post-doctoral candidates:
david.dombrowicz@inserm.fr
Team members :
Team Director
Dr. David DOMBROWICZ
Post-doctoral researchers
- Dr. Laurent L'HOMME
- Vance Gao
Thesis students
- Valentine Guinot
Engineers and Assistant Engineers
- Sébastien FLEURY
- Samuel PIC
- Sandrine QUEMENER
- Marie-Laure JOSEPH