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Research interest

Our team aims to identify new hormonal systems, which coordinate insulin sensitivity and mitochondria biology/energetics across tissues. More specifically we study novel hormones and blood factors mediating the cross talk between liver and adipose tissue in response to feeding cues, such as fasting-refeeding, caloric restriction and obesigenic diets. Our research aims to increase the understanding of the complex physiology of feeding and energy balance and directly works on the development of new therapeutics factors of T2Diabetes and the new diagnostic biomarkers of early diabetes. In hypothesis-driven approaches we perform all steps from the discovery to preclinical testing of novel metabolic factors. The successful candidate will utilize basic molecular biology, biochemistry methods, recombinant protein and adeno-, AAV, lentiviral systems and will work with mouse models of obesity and diabetes. The candidate will work with a young PI, who offers extensive training and mentoring in a highly equipped and multidisciplinary environment.

Project description

Currently, guidelines for diagnosis and treatment of Type 2 diabetes mellitus (T2DM) do not differentiate between sexes. T2DM is more frequently diagnosed at lower age and body mass index in men; however, the most prominent risk factor, which is obesity, is more common in women. Longitudinal studies in humans and mouse models of obesity have shown that females show delayed appearance of insulin resistance despite obesity, compared to males. Sex hormones and epigenetic factors are known to have a great impact on insulin signaling and energy metabolism. In the current project we focus on adipocyte cell-autonomous and sex hormones independent physiological pathways, which underlie sexual dimorphic responses during development of obesity and insulin resistance. We have recently discovered the role of adipocyte acting metalloproteases in this process, and we have already developed transgenic animals to study their role. The candidate will follow an interatomic approach to identify interaction partners and cleaved proteins targeted by those metalloproteases. In addition, he/she will develop enzymatic (high throughput) assays for identification of small molecules, which can affect metalloprotease activity. Finally, the candidate will work with transgenic mice, diabetic mouse models, ovariectomy and gonadectomy mouse models.

Selected Publications

2017 : Duteil D, Tosic M, Willmann D, Georgiadi A, Kanouni T, Schüle R. Lsd1 prevents age-programed loss of beige adipocytes. Proc Natl Acad Sci U S A. 2017 May 16;114(20):5265-5270.

2016: Bosma M, Gerling M, Pasto J, Georgiadi A, Graham E, Shilkova O, Iwata Y, Almer S, Söderman J, Toftgård R, Wermeling F, Boström EA, Boström PA. FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice. Nat Commun. 2016 Apr 12;7:11314

2014: Tjeerdema N, Georgiadi A, Jonker JT, van Glabbeek M, Alizadeh Dehnavi R, Tamsma JT, Smit JW, Kersten S, Rensen PC. Inflammation increases plasma angiopoietin-like protein 4 in patients with the metabolic syndrome and type 2 diabetes. BMJ Open Diabetes Res Care. 2014 Dec 3;2(1):e000034.

Mattijssen F, Georgiadi A, Andasarie T, Szalowska E, Zota A, Krones-Herzig A, Heier C, Ratman D, De Bosscher K, Qi L, Zechner R, Herzig S, Kersten S. Hypoxia-inducible lipid droplet-associated (HILPDA) is a novel peroxisome proliferator-activated receptor (PPAR) target involved in hepatic triglyceride secretion. J Biol Chem. 2014 Jul 11;289(28):19279-93.

Roberts LD, Boström P, O'Sullivan JF, Schinzel RT, Lewis GD, Dejam A, Lee YK, Palma MJ, Calhoun S, Georgiadi A, Chen MH, Ramachandran VS, Larson MG, Bouchard C, Rankinen T, Souza AL, Clish CB, Wang TJ, Estall JL, Soukas AA, Cowan CA, Spiegelman BM, Gerszten RE. β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors. Cell Metab. 2014 Jan 7;19(1):96-108.

2013 : Georgiadi A, Wang Y, Stienstra R, Tjeerdema N, Janssen A, Stalenhoef A, van der Vliet JA, de Roos A, Tamsma JT, Smit JW, Tan NS, Müller M, Rensen PC, Kersten S. Overexpression of angiopoietin-like protein 4 protects against atherosclerosis development.

2012 : Georgiadi A, Boekschoten MV, Müller M, Kersten S. Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart. Physiol Genomics. 2012 Mar 19;44(6):352-61. 

Buler M, Aatsinki SM, Skoumal R, Komka Z, Tóth M, Kerkelä R, Georgiadi A, Kersten S, Hakkola J. Energy-sensing factors coactivator peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and AMP-activated protein kinase control expression of inflammatory mediators in liver: induction of interleukin 1 receptor antagonist. J Biol Chem. 2012 Jan 13;287(3):1847-60.

2010 : Lichtenstein L, Mattijssen F, de Wit NJ, Georgiadi A, Hooiveld GJ, van der Meer R, He Y, Qi L, Köster A, Tamsma JT, Tan NS, Müller M, Kersten S. Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages. Cell Metab. 2010 Dec 1;12(6):580-92.

Georgiadi A, Lichtenstein L, Degenhardt T, Boekschoten MV, van Bilsen M, Desvergne B, Müller M, Kersten S. Induction of cardiac Angptl4 by dietary fatty acids is mediated by peroxisome proliferator-activated receptor beta/delta and protects against fatty acid-induced oxidative stress. Circ Res. 2010 Jun 11;106(11):1712-21

Reviews: Scheideler M, Herzig S, Georgiadi A. Endocrine and autocrine/paracrine modulators of brown adipose tissue mass and activity as novel therapeutic strategies against obesity and type 2 diabetes. Horm Mol Biol Clin Investig. 2017 Aug 29;31(2). 

Boström PA, Graham EL, Georgiadi A, Ma X. mpact of exercise on muscle and nonmuscle organs. IUBMB Life. 2013 Oct;65(10):845-50

Georgiadi A, Kersten S. Mechanisms of gene regulation by fatty acids. Adv Nutr. 2012 Mar 1;3(2):127-34