22.3. 2018, Mitochondriální fyziologie

PhD project: The role of immune system in pulmonary hypertension

The main feature of pulmonary arterial hypertension is arterial wall remodeling towards thickening of vessel wall that leads to an increase of pulmonary arterial pressure, right ventricular hypertrophy, its failure and premature death. Remodeling of artery wall is complex and changes in energy metabolism and apoptotic resistance of cells within wall layers leading to cell hyperproliferation are part of it. Recent studies recognized pro-inflammatory reactions of immune cells as participants in wall remodeling.   In collaboration with US partner, we study fibroblasts from adventitia as a major player in attraction and activation of immune cells. We use unique animal model of calves with hypoxia induced pulmonary hypertension. This study will investigate involvement of metabolic changes in fibroblasts in production of cytokines and further interplay with cells of immune system. This should contribute to understanding of pulmonary hypertension development that can uncover potential target(s) for pharmacology.

Candidate´s profile (requirements):

MSc degree or equivalent in cell biology, physiology or related fields with self-motivation for the biomedical research and interest in short stay in collaborating laboratory in US.

Relevant publications:

•D'Alessandro A, El Kasmi KC, Plecitá-Hlavatá L, Ježek P, Li M, Zhang H, Gupte SA, Stenmark KR. Hallmarks of Pulmonary Hypertension: Mesenchymal and Inflammatory Cell Metabolic Reprogramming. Antioxid Redox Signal. 2018 Jan 20;28(3):230-250.

•Plecitá-Hlavatá L, D'alessandro A, El Kasmi K, Li M, Zhang H, Ježek P, Stenmark KR. Metabolic Reprogramming and Redox Signaling in Pulmonary Hypertension. Adv Exp Med Biol. 2017;967:241-260.

•Zhang H, Wang D, Li M, Plecitá-Hlavatá L, D'Alessandro A, Tauber J, Riddle S, Kumar S, Flockton A, McKeon BA, Frid MG, Reisz JA, Caruso P, El Kasmi KC, Ježek P, Morrell NW, Hu CJ, Stenmark KR. Metabolic and Proliferative State of Vascular Adventitial Fibroblasts in Pulmonary Hypertension Is Regulated Through a MicroRNA-124/PTBP1 (Polypyrimidine Tract Binding Protein 1)/Pyruvate Kinase Muscle Axis. Circulation. 2017 Dec 19;136(25):2468-2485.

•Plecitá-Hlavatá L, Tauber J, Li M, Zhang H, Flockton AR, Pullamsetti SS, Chelladurai P, D'Alessandro A, El Kasmi KC, Ježek P, Stenmark KR. Constitutive Reprogramming of Fibroblast Mitochondrial Metabolism in Pulmonary Hypertension. Am J Respir Cell Mol Biol. 2016 Jul;55(1):47-57

•Li M, Riddle S, Zhang H, D'Alessandro A, Flockton A, Serkova NJ, Hansen KC, Moldvan R, McKeon BA, Frid M, Kumar S, Li H, Liu H, Caánovas A, Medrano JF, Thomas MG, Iloska D, Plecitá-Hlavatá L, Ježek P, Pullamsetti S, Fini MA, El Kasmi KC, Zhang Q, Stenmark KR. Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1. Circulation. 2016 Oct 11;134(15):1105-1121.

Supervisor: Lydie Plecitá-Hlavatá,PhD.