PhD SP3

Mechanism of hyperglycemic control of histone code in metabolic inflammation and microvascular complications

Supervisor (Mannheim): Julia Kzhyshkowska
Co-Supervisor (Groningen): Marco Harmsen
Graduate: Luis Ernesto Garcia

Project description

Histone code is an essential mechanism of epigenetic memory induced by diabetic conditions. Pharmacological targeting of epigenetic networks to reduce cardiovascular disease was suggested. However, the gap of knowledge is the role of the histone code in the pathological macrophage/endothelial cells interactions in hyperglycemic conditions resulting in vascular diabetic complications. We aims of the PhD project are: 1) to identify histone-modifying enzymes responsible for the hyperglycemia-induced epigenetic changes in macrophages; 2) to identify the reversibility of hyperglycemic memory fixed in the histone code, 3) to identify the effect of the blockade of histone modifying enzymes on the macrophages/endothelial functional interactions. 

References

1. *Ovsiy I et al, Sci Rep. 2017 Dec 4;7(1):16847.
2. *Moganti K, Li F et al Immunobiology. 2017 Oct;222(10):952-959.
3. *Riabov V, et al. Acta Biomater. 2017 Apr 15;53:389-398.
4. *Rendra E et al. Immunobiology. 2018 Dec 1.
5. Lapenna A et al. Nat Rev Immunol. 2018 Nov;18(11):689-702
6. Davis FM and Gallagher KA. Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):623-634.
7. Rajasekar P et al. 1, O'Neill CL. J Diabetes Res. 2015;2015:436879

*Own Publications

Methods used

1. molecular biology, epigenetic, protein-protein interaction, immunological and advanced imaging techniques, including chromatic immunoprecipitation, RT-PCR, flow cytometry, confocal microscopy
2. mouse models for hyperglycemia and diabetic complication
3. functional analysis of primary mouse and human macrophages and endothelial cells
4. analysis of monocytes from patients with diabetes and complications

Collaboration Partners

• Peter Nawroth and Thomas Fleming, University of Heidelberg
• Marianne Rots, University Medical Centre Groningen
• Benito Yard, Mannheim