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After a heart attack (also called myocardial infarction), the heart forms a scar as part of its healing process. This can sometimes lead to dangerous complications like heart failure or heart rhythm disorders. The immune system, particularly B cells interacting with other cells like monocytes and platelets, plays a crucial role in this healing process. Most research on this topic comes from mouse studies, but how it applies to humans is unclear.

This research project focuses on the unwanted side effects of immunotherapy, which activates the immune system to fight cancer. These side effects, known as immune-mediated adverse events (irAEs), can interfere with or necessitate the discontinuation of life-saving cancer therapies. The aim of the project is to identify new molecular targets in various  tissue affected by irAEs (skin, intestine, liver, etc.) as well as patients’ blood.

In the MalheuR project, Karolina Gente and her team are investigating how cancer patients with rheumatic diseases can be given the best possible treatment. Since 2018, more than 1,200 patients in Heidelberg have been registered to enable a systematic analysis of the interactions between cancer and rheumatic diseases. The interdisciplinary research team is using clinical data and blood samples to identify biomarkers that may allow more precise treatment decisions.

CAR-T cells are engineered immune cells designed to specifically target and destroy cancer cells. While they have shown great success in treating blood cancer, they face significant challenges in solid tumors. These challenges include limited penetration into the tumor and functional suppression by the tumor microenvironment. In this project, the researchers combine CAR-T cells with agents that stimulate the innate immune system, which could enhance the efficacy of CAR-T cells in solid tumor settings.

TMEM70 deficiency is a mitochondrial genetic condition that display a detrimental impact on cardiac function. It participates in the assembly of ATP synthase, which is responsible for most energy generation provided by mitochondria. Patients with TMEM70 mutations have a high incidence of cardiac disease and early-onset death. Unfortunately, therapeutic interventions remain elusive, and are limited to symptomatic and supportive care. The researchers suggest the chemical AMPK modulation as a potential therapeutic strategy.

Pathological cardiac fibrosis is a common coexisting condition in cardiovascular diseases. There are currently no therapies that can directly reverse fibrosis. The team of scientists has shown that the transcription factor Sox9 plays a crucial role in scar formation after a heart attack. However, the exact mechanisms by which it regulates cardiac fibrosis are still unclear. Cardiac fibroblasts produce extracellular matrix (ECM) after injury, and an excessive deposition of ECM leads to pathological fibrosis.

Cardiac magnetic resonance imaging (MRI) has become indispensable for the diagnosis and assessment of many cardiovascular diseases. However, during the time-consuming examination, repeated breath-holding is necessary for the image acquisition. Moreover, the extensive examination can only be carried out by specially trained personnel. Artificial intelligence (AI) methods could make a decisive contribution to overcoming these limitations.

In light of the increasing life expectancy and the associated increase in individuals with cognitive impairment (e.g., dementia), there is a growing importance to understand and prevent cognitive decline in older adults. The objective of the current project is to identify individual profiles of demographic, lifestyle and health-related factors that are collectively responsible for the maintenance of brain structure and cognitive performance in older males and females. It will first be tested whether the profiles are adequate predictors of cognitive performance.

Highly potent broadly neutralizing antibodies are a promising option for the treatment and prevention of HIV infection. Similar to available antiretroviral drugs, however, antibodies must be administered regularly due to their limited half-life. This project therefore aims to develop effective strategies for the endogenous expression of broadly neutralizing antibodies. To achieve durable sustained production of combinations of antibody-based agents after a single administration, optimized gene vectors based on adeno-associated viruses (AAV) will be generated.

In modern intensive care medicine, we have the ability to replace most organs at least temporarily and to remove various toxins and harmful substances from the bloodstream. These options range from dialysis in kidney failure to liver dialysis in liver failure, as well as the use of adsorption devices to eliminate substances such as cytokines, bilirubin, or myoglobin. To enable a more targeted use of these procedures in the future, the function of each device and the underlying disease must be understood in detail.