Inhaltspezifische Aktionen

CardioMetabolism and Bioenergetics (Pavez-Giani)

CardioMetabolism and Bioenergetics

Research focus

The CardioMetabolism and Bioenergetics group investigates how mitochondrial function and cellular energy flux govern cardiac development, adaptation, and disease. Our research is grounded in translational bioenergetics, aiming to define and therapeutically reprogram bioenergetic states to restore cellular function in human disease.
We focus on cardiogenetic disorders driven by mitochondrial dysfunction, including defects in oxidative phosphorylation and ATP synthase assembly, as well as the impact of mtDNA heteroplasmy on cardiac bioenergetics. Using human induced pluripotent stem cells (hiPSCs) and advanced cardiac assembloid models, we recapitulate disease in a human, developmentally relevant context. These systems enable us to capture critical transitions in mitochondrial function during cardiomyocyte maturation and to identify heteroplasmy-dependent thresholds that drive energetic collapse. Our work integrates high-resolution bioenergetic and multi-omics approaches, including metabolic flux analysis, native complexomics, proteomics, metabolomics, and transcriptomics, to map how energy metabolism is rewired in disease. We are particularly interested in how mitochondrial structural defects and heteroplasmy levels converge on impaired membrane potential, respiratory capacity, and calcium handling. A central objective of the lab is to translate these insights into targeted therapeutic strategies, including metabolic modulation, activation of adaptive signaling pathways, and gene-regulatory approaches. By linking mechanism to functional rescue, we aim to establish broadly applicable strategies to correct bioenergetic failure in mitochondrial and cardiometabolic disease.

Team

Dr. Mario Pavez-Giani, PhD

Dr. Mario Pavez-Giani, PhD

Junior Group Leader | Principal investigator

mario.pavez-giani@uni-giessen.de
Dr. Esteban Palacios-Contreras

Dr. Esteban Palacios-Contreras

Postdoctoral Researcher

Project: "Pharmacological Resolution of the Mitochondrial Metabolic Cliff: Reversing Pathological Remodeling in mtDNA-related Cardiomyopathy"

Maedeh Ahmadirouzbahani

Maedeh Ahmadirouzbahani

Master student

Project: "Preclinical research into new treatment methods for cardiomyopathy caused by Complex V deficiency."

We are always seeking passionate and driven medical, master and PhD students who are interested in completing a thesis, and joining our translational research team.
If a topic resonates with you, please do not hesitate to reach us out via email – we’d be happy to hear from you!

Selected Publications

  1. Fell J.*, Pavez-Giani MG.*, … Hasenfuss G., Zimmermann WH., Wollnik B., Cyganek L. Targeting Interleukin-8 mediated cellular crosstalk reverses hypertrophic cardiomyopathy and cardiac fibrosis in Noonan syndrome. Circulation 2026 Apr 16. doi: 10.1161/CIRCULATIONAHA.125.074155.
  2. Pavez-Giani M. and Zelarayán L. Zeb2os: A Noncoding Obstacle to Healing Hearts. Circ Res. 2026;138:e328125. 2026 Feb 27;138(5):e328125. doi: 10.1161/CIRCRESAHA.126.328125. 
    Schogen E., … Pavez-Giani MG., Doroudgar S., Sossalla S. and Zelarayán L. Enhancing KLF15 Activity in Cardiomyocytes: A Novel Approach to Prevent Pathological Reprogramming and Fibrosis via Nuclease-Deficient dCas9VPR. Sig Transduct Target Ther. 2026 Mar 3;11(1):76. doi: 10.1038/s41392-026-02593-9.
  3. Zink, Annika; Dai, Dao-Fu; Wittich, Annika; Henke, Marie-Thérèse;…Pavez-Giani, Mario… et al. (2025): Pluripotent stem cell-based drug discovery uncovers sildenafil as a treatment for mitochondrial disease. Cell. 2026 Mar 19;189(6):1656-1679.e42. doi: 10.1016/j.cell.2026.02.008.
  4. Dobner J., Nguyen T., Pavez-Giani MG, Cyganek L., Distelmaier F., Krutmann J., Prigione A., Rossi A. mtDNA analysis using Mitopore. Mol Ther Methods Clin Dev. 2024 Mar 12;32(2):101231. 
    Bomer N*, Pavez-Giani MG*, Grote Beverborg N, Cleland J, van Veldhuisen DJ, van der Meer P. Micronutrient deficiencies in heart failure: mitochondrial dysfunction as a common pathophysiological mechanism? J Intern Med. 2022 Jun;291(6):713-731. 
    Pavez-Giani MG and Cyganek L. Recent Advances in Modeling Mitochondrial Cardiomyopathy Using Human Induced Pluripotent Stem Cells. Front Cell Dev Biol. 2022 Jan 10;9:800529
  5. Bomer N*, Pavez-Giani MG*, Hoes MF, Deiman FE, Piek A, Simonides W, Boer RA, Berezikov E, Westenbrink D, Silljé HWH, van der Meer P. Identification of DIO2 as a regulator of metabolic reprogramming and mitochondrial function in heart failure. Int J Mol Sci. 2021 Nov 2;22(21):11906.
  6. Pavez-Giani MG, Sánchez-Aguilera PI, Bomer N, Miyamoto S, Booij HG, Giraldo P, Oberdorf-Maass SU, Nijholt KT, Yurista SR, Milting H, van der Meer P, Boer RA de, Heller Brown J, Sillje HWH, Westenbrink BD. ATPase Inhibitory Factor-1 Disrupts Mitochondrial Ca2+ Handling and Promotes Pathological Cardiac Hypertrophy through CaMKIIδ. Int J Mol Sci 2021;22.