Program

The circadian clock, our endogenous time-generating system, regulates behavioral, physiological, and cellular processes. Disruptions to this clock, such as those caused by shift work, jet lag, or genetic alterations, are associated with an increased risk of various diseases, including obesity, diabetes, cardiovascular diseases, and cancer. Circadian medicine, the study of how time affects health and disease, has emerged as a promising approach to enhance health and performance and to optimize treatment timing. However, the potential of circadian medicine is limited by the lack of non-invasive tools for characterizing the circadian clock.
 To address this challenge, we developed TimeTeller, a non-invasive methodology to analyze circadian rhythms. Currently employed in various clinical studies, TimeTeller profiles circadian rhythms based on gene expression measurements. Through mathematical modeling and bioinformatics analysis, we derive predictions regarding optimal time windows for performance and treatment administration.
 By aligning an individual's circadian clock with optimal times for daily routines and incorporating personal health information across lifestyle, care, and research settings, we can improve physical and mental performance and enhance the effectiveness of certain therapies.

The mammalian intestine contains trillions of microbes, a community that is dominated by members of the domain Bacteria but also includes members of Archaea, Eukarya, and viruses. The vast repertoire of this microbiome functions in ways that benefit the host. The mucosal immune system co-evolves with the microbiota beginning at birth, acquiring the capacity to tolerate components of the community while maintaining the capacity to respond to invading pathogens. The gut microbiota is shaped and regulated by multiple factors including our genomic composition, the local intestinal niche and multiple environmental factors including our nutritional repertoire and bio-geographical location. Moreover, it has been recently highlighted that dysregulation of these genetic or environmental factors leads to aberrant host-microbiome interactions, ultimately predisposing to pathologies ranging from chronic inflammation, obesity, the metabolic syndrome and even cancer. We have identified various possible mechanisms participating in the reciprocal regulation between the host and the intestinal microbial ecosystem, and demonstrate that disruption of these factors, in mice and humans, lead to dysbiosis and susceptibility to common multi-factorial disease. Understanding the molecular basis of host-microbiome interactions may lead to development of new microbiome-targeting treatments.

This seminar will highlight groundbreaking findings from four recent Randomized Controlled Trials (RCTs) – DIRECT, CASCADE, CENTRAL, and DIRECT PLUS – exploring the significant impacts of lifestyle and dietary interventions on aging. The  2-year Dietary Intervention Randomized Controlled Trial (DIRECT) and  a 4-year follow-up (A Dietary Intervention- Randomized Controlled Trial (DIRECT) Study), compared the effects of dietary strategies on cardiometabolic risk and plaque regression. The 2-year CASCADE trial(The CArdiovasCulAr Diabetes & Ethanol (CASCADE) Trial), addressed the effect of moderate alcohol in type 2 diabetes. The  CENTRAL (Diet and Body Composition (CENTRAL)) whole-body MRI trial focused on dynamic of human-specific fat depots and fuel metabolism across dietary strategies. The DIRECT PLUS trial (Effects of Green-MED Diet Via the Gut-fat-brain Axis (DIRECT-PLUS)) explored the effect of the diet and specific high- polyphenols foods as Mankai on the gut-fat-brain axis. In this trial, new horizons were explored related to Autologous Fecal Microbiota Transplantation, brain atrophy attenuation, and epigenetics. The talk will discuss transformative effects of various dietary interventions to significantly reduce age-related health decline. The seminar will cover reductions in vascular stiffness, carotid atherosclerosis, and brain atrophy, emphasizing the role of diet and exercise in promoting cardiovascular and cognitive longevity. The lecture will discuss the crucial role of the gut microbiome in aging and how dietary patterns optimize its composition and will gain insights into epigenetic changes and their influence on biological aging, showcasing how interventions can attenuate the aging process beyond weight loss.

Liquid Biopsy has been defined as the analysis of tumor cells or products released from primary or metastatic tumor tissues into the blood or other body fluids. Over the past ten years, CTCs, ctDNA and extracellular vesicles have received enormous attention as new biomarkers and subject of translational research. In particular, CTC and ctDNA research has opened new avenues for a better understanding of tumor biology in cancer patients, including intra-patient heterogeneity and evolution towards resistance to therapy. Although both biomarkers are already used in numerous clinical trials, their clinical utility is still under investigation with first promising results. Clinical applications include early cancer detection, improved cancer staging, early detection of relapse, real-time monitoring of therapeutic efficacy and detection of therapeutic targets and resistance mechanisms. In particular, interventional clinical studies are required to demonstrate clinical utility of liquid biopsy as an important prerequisite for the introduction of this new diagnostic approach into clinical practice. Moreover, assay harmonization and standardization as conducted by international consortia like the European Liquid Biopsy Society (ELBS; www.elbs.eu) is essential. Here, I will discuss the potential and current challenges of liquid biopsy research for understanding human cancer biology and the implementation of this new diagnostic approach into clinical studies with emphasis on solid tumors.

Chronic inflammatory disease (e.g. Inflammatory Bowel Disease, rheumatoid Arthritis, etc.) are characterized by a systemic disease behavior requiring long-life pharmacological intervention. Despite the introduction of targeted therapies (e.g. anti-TNF, anti-IL12/23, etc.) the overall long-term remission rate is low and leads to frequent changes in drug therapy. Although several strategies are pursued to develop biomarker for individual therapy stratification, the path towards clinical implementation of molecular biomarker into routine medicine is still unclear. Within the “Molecular Inflammation Board on stage” we will discuss and exemplify in real-world IBD cases, how implementation of molecular medicine can be translated into patient care.