Pawel Swietach

Pawel Swietach studies how the chemical microenvironment—especially pH, oxygen and core metabolites—governs cell function across the heart, cancers and blood. His group integrates imaging, physiology, quantitative modelling and bespoke assays to connect discovery with translation. Cardiac physiology and metabolism. The Group has studied how localized proton signals shape cardiac function by coupling to calcium handling and energetics. Landmark studies revealed coupled Ca²⁺/H⁺ transport on mobile cytoplasmic buffers, providing a mechanism for acid–calcium crosstalk in myocytes, and identified a carbonic-anhydrase–rich extramitochondrial domain that improves CO₂ venting, preserves matrix pH and supports myocardial energetics. More recently, the lab linked propionate metabolism to epigenetic remodeling in the heart—histone propionylation/acetylation with transcriptional and functional consequences—highlighting how metabolites program cardiac performance. Key diseases of focus are inherited disorders, notably propionic acidemia, and conditions including diabetes, ischaemia, and maladaptive hypertrophy. Cancer pH biology. The Group has made major contributions in defining acidity as a driver of tumour progression and selection. Recent milestones uncovered stromal mechanisms that vent tumour-generated acid through anion exchangers and gap-junctional networks—relieving the energetic burden on cancer cells and shaping invasion niches, as well as adaptive mechanisms that enable cells to acquire an acid-resistant phenotype and thrive in otherwise harsh conditions. Ongoing efforts are focusing on how to exploit acidic microenvironments as therapeutic and diagnostic opportunities. Blood and oxygen transport. An highly translational programme quantifies how red cells pick up and release oxygen. Single-cell O₂-exchange imaging established that cytoplasmic diffusion—restricted by haemoglobin and pathlength—is an important barrier to gas transport. Building on this biophysics, the lab developed FlowScore, a flow-cytometric proxy of O₂-unloading kinetics intended to grade the functional quality of stored blood. These tools aim to match donors to patients more effectively and to inform storage strategies. Key beneficiaries of our research include blood banks, and transfusion and transplant medicine.

[2025] Acidosis attenuates the hypoxic stabilization of HIF-1α by activating lysosomal degradation. White B. et al, (2025), J Cell Biol, 224 [2025] Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of blood. Rabcuka J. et al, (2025), EBioMedicine, 111 [2024] CRISPR-Cas9 screen identifies oxidative phosphorylation as essential for cancer cell survival at low extracellular pH. Michl J. et al, (2024), Cell Rep, 43 [2024] Phenotypic screen of sixty-eight colorectal cancer cell lines identifies CEACAM6 and CEACAM5 as markers of acid resistance. Michl J. et al, (2024), Proc Natl Acad Sci U S A, 121 [2024] Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells.