Breast cancer affects 1 in 7 women, and the risk of death from metastatic (stage 4) disease remains high. In recent years, chemotherapy and mastectomy have improved the overall survival of breast cancer patients and reduced the incidence of breast cancer in at-risk individuals. However, these treatments are non-specific, and do not eliminate the risk of cancer development, patient relapse, or...
Targeted metabolomics workflows are often constrained by limited analyte coverage and high per-sample costs of commercial kit-based assays, leading to incomplete metabolic insights. Here, we present a comprehensive and cost-efficient targeted metabolomics platform that combines broad analyte coverage with high throughput across diverse biological matrices. Utilizing the MetaSci Complete...
Immunotherapy has revolutionized cancer treatment, yet its efficacy remains limited to a subset of patients due to tumor-intrinsic resistance, variable immune responses, and a suppressive tumor microenvironment (TME). To address this challenge, we are developing a patient-centric reporting system that initially integrates comprehensive genomic and transcriptomic profiling to inform clinical...
Currently, theranostic options for triple-negative breast cancer (TNBC) are critically lacking. As a promising strategy, the KiSS-1 receptor (KiSS-1R) has been reported for potential molecular imaging and targeted radionuclide therapy. The interaction of kisspeptins (KPs) and their receptor (KiSS-1R) is vital for the reproductive axis and has been reported to exhibit tumor-suppressing...
Introduction
Sleep disturbances and chronotype have been implicated in cancer-related outcomes, yet their impact on health-related quality of life (HRQoL) in colorectal cancer (CRC) patients remains underexplored. This study examines longitudinal associations between sleep characteristics, chronotype, and HRQoL in early onset (EO) (≤50 years) and late onset (LO) (>50 years) CRC...
Spinal cord injury (SCI) is a debilitating neurological condition resulting in partial or complete loss of motor and sensory function. Its complex pathophysiology, involving both immediate mechanical damage and secondary degenerative processes, presents major challenges for treatment. Among neuroregenerative approaches, anti-Nogo-A antibody (NG101) therapy promotes axonal regeneration and has...
Inflammatory Bowel Diseases (IBD), including Crohn’s disease and ulcerative colitis, have been estimated to affect between 10 and 40 per 100.000 people in Europe, with an increasing burden over the last few decades [1]. The presence of chronic inflammation associated to these diseases is a known risk factor for the development of colorectal cancer [2]. In this work, we seek to better...
Tumors are complex ecosystems shaped by both the identity and spatial organization of diverse cell types. Understanding how these factors evolve during cancer progression may help reveal coordinated multicellular behaviors linked to disease outcome. In this study, we profiled 522 colorectal samples using multiplexed ion beam imaging (MIBI-TOF) and a 42-marker panel capturing cell lineage,...
Introduction and aim: The translation of new radiotracers into clinical application use is a complex and often daunting process. The core function of a multidisciplinary team is to bring together professionals with expertise in several areas to expand diagnostic and treatment options for patients. One such tracer, [89Zr]Zr-DFO-trastuzumab, has been successfully implemented in other...
Pairs of individuals who live together for long periods of time, e.g., spouses, tend to share similar lifestyles, behaviours, and risk events. As environmental exposures can affect the epigenome, it is hypothesised that pairs of long-term cohabiting couples may exhibit greater similarity in their DNA methylation marker patterns.
Using the ESTHER study, a population-representative cohort...
Due to the high variation in surface receptor expression, breast cancer (BCa) is a highly heterogeneous disease presenting significant challenges for early detection and treatment. Four molecular subtypes have been identified including estrogen receptor (ER)- and progesterone receptor (PR)-positive BCa. ER and PR are overexpressed in ≈ 80% of all BCa which promotes cell proliferation. The...
More than 150 proteins contribute to the formation and regulation of various RNA modifications in humans. These modifications play a crucial role in cell function by influencing RNA splicing, stability, translocation, translation, and ultimately gene expression. To explore the impact of RNA-modifying proteins on cancer cell function, we conducted comprehensive CRISPR-Cas9 dropout screens...
Background and Aims: The prognostic value of body mass index (BMI) in colorectal cancer (CRC) remains debated, partly due to disease-related weight loss. DNA methylation (DNAm)-based biomarkers that reflect long-term adiposity may offer more stable prognostic insights. We aimed to evaluate whether blood-based DNAm-BMI scores are associated with mortality in CRC patients and how they compare to...
The development of immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitors (ICIs) cause morbidity, necessitates treatment cessation and limits ICI efficacy. Comparing different first- and second-line irAE treatments, we found that glucocorticosteroids, TNFα blockade, and α4β7-integrin inhibition reduced anti-tumor immunity in mice. We compared these...
We investigated two competing terms for influenza in English, Spanish, German, French, and Italian: "influenza" and "grippe" to determine what may have driven the choice in disease name under these competing options. Of the two, "grippe" is more commonly used in Indo-European languages. Using minimum edit distance (Levenshtein distance) we determined the available space in each language for an...
The African trypanosome, T. brucei, is a unicellular pathogen responsible for sleeping sickness in humans and nagana in animals. Following transmission by the tsetse fly, the parasite replicates extracellularly in the bloodstream, where it faces constant exposure to the host's immune response. To evade this immune challenge, T. brucei employs an effective strategy of antigenic variation,...
The quantification of therapeutics and associated biomarkers is crucial for understanding drug efficacy and patient response in personalized medicine, and in clinical studies. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers unique advantages for high resolution quantitative analysis of small-molecules, peptides and even proteins that are used as therapeutics (including...
Identifying major histocompatibility complex (MHC)-bound peptides recognized by specific T-cell receptors (TCRs) is key to developing personalized T-cell therapies. We developed an unbiased pipeline combining immunopeptidomics with TCR functional assays in pancreatic ductal adenocarcinoma (PDAC). MHC class I peptides were fractionated by liquid chromatography (LC) and identified via mass...
High-risk human papillomaviruses (HPVs) are involved in cervical and oropharyngeal cancers, causing over 730 000 new cases and 350 000 deaths worldwide every year. The viral oncoproteins E6 and E7, essential for induction and maintenance of the malignant phenotype, are ideal therapy targets. Proteolysis Targeting Chimeras (PROTACs) are small molecules triggering proteasomal degradation of...
Genetic engineering of T cells to express tumor antigen-specific T cell receptors (TCRs) is a promising approach in cancer immunotherapy. While the cytotoxic potential against cancer of these engineered TCR T cells is critical, their therapeutic efficacy also depends on their ability to migrate, infiltrate, proliferate, and persist within the complex tumor microenvironment (TME). This is...
The tumor microenvironment (TME) is a complex and dynamic ecosystem composed of cancer cells, stromal cells, immune cells, various signaling molecules, and extracellular matrix components. Dynamic processes within the solid TME drive response or resistance to treatment, highlighting the importance of developing tools capable of precisely targeting these intricate mechanisms. Beyond...
Anelloviruses are circular ssDNA viruses and endemic in the human population, causing persistent, yet dynamic infections. Due to the lack of in vitro models, their interaction with the human host, namely the innate immune system, is largely unknown. However, they must be under constant control through (innate) immune mechanisms, since immunosuppression leads to viral rebound. To date,...
Diacylglycerol kinases (DGKs), specifically DGK zeta (DGKζ) and DGK alpha (DGKα), are lipid kinases that regulate T-cell activation by modulating diacylglycerol (DAG) levels at the immunological synapse in a non-redundant fashion. T-cells deficient for DGKζ or DGKα are hyperresponsive and were shown to mediate enhanced immunity against viral infections and tumors. Further experimental evidence...
To overcome stress-induced protein imbalance, cells have evolved a protective mechanism called the heat shock response (HSR). In mammals, this response is primarily regulated by heat shock transcription factor 1 (Hsf1). Under stress conditions, Hsf1 activates genes involved in various cellular processes, including protein folding and degradation, membrane organisation, chromatin regulation,...
Objective:
Cancer-related fatigue is one of the most common burdens of cancer patients. To date, most studies focused on fatigue during or after cancer treatment. However, investigating pretreatment fatigue may identify underlying factors beyond cancer therapy and enable timely fatigue management.
Methods: 232 breast cancer patients and 41 healthy women were recruited via the NCT Heidelberg...
Biomolecular condensates formed via phase separation are emerging as key modulators of signal transduction. In Wnt signaling, Dishevelled proteins (DVL), particularly DVL2, form such condensates ("signalosomes") upon pathway activation, but how these condensates are regulated remains poorly understood. This project investigates the regulatory roles of casein kinase 1 (CK1) and the RNA helicase...
The world is aging, and improving the health of the elderly is crucial. Elderly individuals are particularly susceptible to immune system failure, leading to increased vulnerability to infectious diseases. Immune responses exhibit sex-specific patterns due to a combination of hormonal and genetic factors, including the number of X chromosomes and the expression of genes escaping X-inactivation...
Menin inhibitors represent a novel class of targeted therapies for acute myeloid leukemia (AML), particularly in patients with KMT2A rearrangements (KMT2A-r) and NPM1 mutations (NPM1mut). These inhibitors disrupt the Menin-KMT2A complex, silencing leukemogenic gene expression, promoting differentiation, and leading to disease eradication. However, the precise mechanisms by which the...
In vivo gene delivery has emerged as powerful tool for novel therapeutic concepts. A major challenge is the development of vectors capable of mediating highly selective gene transfer specifically into therapy-relevant cells. For this purpose, we have developed the concept of rational-based receptor-targeting of AAV vectors harnessing designed ankyrin repeat proteins (DARPins) in order to...
Background: Our study explored the pathway from nutrition literacy through diets up to nutritional status and hemoglobin levels of adolescents and youth in SSA.
Methods: The study used data from the ARISE-NUTRINT cohort, which was collected in 2024. A total of 9019 participants aged 10 – 24 years were recruited from seven SSA countries. Principal component analysis was used to identify...
In diabetic patients, factors such as dyslipidemia and hypoxia drive kidney damage. Our previous research using induced renal epithelial cells (iRECs) and a pharmacological mouse model of diabetes combined with a high-fat diet demonstrated that palmitic acid (PA), a saturated fatty acid induces ER stress and lipotoxicity in proximal tubular cells in vitro and in vivo, whereas monounsaturated...
Pancreatic ductal adenocarcinoma (PDAC), responsible for over 90% of pancreatic cancer cases, remains one of the deadliest cancers, with a 5-year survival rate of just ~11%. Its incidence is increasing by 0.5–1% annually due to ageing populations and rising obesity, and it is projected to become the second leading cause of cancer-related deaths.
The Reichert lab at the Technical University of...
Although most cells of an organism carry the same genetic content, they show diverse properties, develop distinct functions and form different tissues. This is enabled by gene regulation, the precise timely and spatially controlled activation and repression of genes. However, how cell-type specific transcriptional induction of genes is initiated, is still not fully understood. One factor...
ZBTB7A is a transcription factor critical for hematopoietic lineage commitment, particularly in promoting erythroid differentiation. In acute myeloid leukemia (AML), ZBTB7A mutations are frequently associated with the t(8;21) translocation, which generates the RUNX1::RUNX1T1 fusion and defines a patient subgroup with relatively favorable outcomes. However, relapse remains a significant...
