Today insulin resistance (IR) is reaching pandemic proportions and it is predicted to emerge a leading worldwide morbidity by 2030. Immune cells, including the so-called adipose tissue macrophages (ATMs) have key roles in the development of this disease. Pharmacological intervention to shape ATM differentiation and function may be a straightforward approach to prevent or combat IR. However the stem cell origin of ATMs is still unclear, which blocks the development of such prevention or treatment strategies. Recent reports show that some specific sets of macrophages develop from embryonic hematopoietic stem cells (eHSCs) and not from the bone marrow as it was postulated before. Our preliminary studies raise the possibility that eHSCs are present in the mouse and the human adipose tissue and these stem cells replenish the ATMs in adulthood. The major scientific objectives of this project are to (a) address the critical question whether ATMs are derived from eHSCs, and (b) define whether the eHSC-derived ATMs can cause IR. These are novel and non-conventional ideas on the determination of IR and are challenging the current wisdom on ATM origin. The deliverables of this project may open a new path to alleviate or prevent IR through eHSCs.

MitO2Health aims to develop and empirically prove a radically new pathophysiological model of Major Depressive Disorder (MDD) as a systemic energy deficiency disease. Traditionally, MDD is conceptualized as a neurotransmitter deficiency in the brain. However, with pioneering methods my group has provided evi-dence for reduced mitochondrial energy production in MDD, characterizing it as a cellular-metabolic disorder with a lowered production of adenosine triphosphate (ATP). Reduced mitochondrial bioenergy production and impairments in oxygen (O2) homeostasis (reduced levels of erythrocytes, less hemoglobin and its lower O2-binding affinity due to oxidative stress), as well as oxidative stress and inflammation (the “MitO2Health parameters”) were consistently associated with an increased risk for MDD, but have been neglected so far in MDD research and therapy. In MitO2Health we will more comprehensively than ever before investigate the physiological mechanisms underlying MDD and will provide first longitudinal evidence on the mutual in-terplay between the MitO2Health parameters and MDD. Moreover, we will apply cognitive-behavioral therapy (CBT) as randomized treatment condition to test whether CBT-related MDD symptom reduction is coupled to a normalization of the MitO2Health parameters. We will treat 100 MDD patients with 6 months of CBT and compare them to 100 MDD patients of a waiting-list group and 100 healthy controls. Clinical and biological status will be assessed at four points over 18 months. We will thus characterize the biomarker pro-files of MDD treatment response and resistance as well as MDD symptom recurrence during a follow-up pe-riod. MitO2Health will not only establish a modern etiological model of MDD, but also identify biomarkers of individual therapy response and relapse. This will lead to new diagnostic standards and inspire personalized MDD treatment concepts that will fundamentally improve clinical outcomes in psychotherapy and psychiatry.

This is a higher education student and staff mobility project, please consult the website of the organisation to obtain additional details.

This is a project for higher education student and staff mobility between Programme Countries and Partner Countries. Please consult the website of the organisation to obtain additional details.