Peter Mirtschink Group
Transcriptional & Metabolic Plasticity in Cardiometabolic Disease
Our research centers on how cellular metabolism and gene regulation converge to drive disease progression in non-communicable, chronic inflammatory disease. By integrating advanced transcriptomic and metabolomic approaches, our work examines how immune cells and e.g. cardiomyocytes adapt their energy pathways during stress conditions such as obesity, diabetes, or ischemic injury. Specifically, we explore how hypoxia-inducible factor (HIF-1 and HIF-2) signalling and non-coding RNAs shape transcriptional programs that either exacerbate or mitigate tissue damage. A second major theme is the development and mechanistic study of RNA-based therapies (e.g., antisense oligonucleotides, siRNAs), focusing on their intracellular trafficking and the potential to precisely modulate disease-driving genes. Ultimately, our goal is to leverage these insights to design personalized interventions targeting cellular metabolism—ranging from small-molecule inhibitors and lipid-lowering agents to next-generation RNA therapeutics—that combat pathological remodeling and chronic inflammation.
Future Projects and Goals
- Project 1: Immunometabolism & Heart Disease
- Profiling metabolic changes in cardiac immune cells post-MI and in LP-induced heart failure
- Investigating HIF isoforms in macrophage vs. neutrophil function and tissue repair
- Project 2: RNA-Based Therapeutics
- Developing siRNA and antisense strategies
- Project: 3 Metabolomics & Precision Medicine
- High-throughput quantitative metabolomics (NMR & MS) to identify signature “metabotypes”
- Linking metabolic fingerprints to therapy responsiveness in heart failure, obesity, diabetes, and fatty liver disease
- Project 4: Hypoxia Signaling as a Druggable Target
- Exploring HIF1α/HIF2α roles in activated neutrophils/macrophages
- Evaluating PHD inhibitors for selective immune modulation in ischemic heart conditions
- Project 4: Regulation of Adipogenesis & Adipocyte Fate by Inflammatory Signalling
- Collaborative effort (with Chavakis & Wolfrum groups) examining how inflammatory stimuli and/or infection epigenetically reprogram adipocyte progenitors
- Investigating “inflammatory memory” in adipocyte precursors, which may predispose to obesity and metabolic dysfunction upon future high-caloric challenge
- Integrating lineage tracing, in vivo infection or LPS models, and state-of-the-art metabolomics to elucidate inflammatory imprinting on adipose tissue development
Methodological and Technical Expertise
- NMR- and LC-MS–based metabolomics (targeted/untargeted)
- Transcriptomics (RNA-seq, ChIP), epigenomics (ATAC-Seq), single-cell analyses
- 7T MRI for metabolic imaging
- Animal models of chronic inflammatory diseases
- Primary cell culture (cardiomyocytes, endothelial cells, immune cells, adipocyte progenitors)
- Advanced metabolic profiling
- Automated pipelines for NMR and LC-MS
- Biomarker discovery, patient stratification, therapy monitoring