Principal Investigator
We aim to understand how distinct types of programmed cell death differentially affect inflammatory responses and disrupt tissue homeostasis to cause disease. Currently, we have a strong focus on the role of cell death-induced inflammation in the regulation of metabolic dysfunction induced by obesity and ageing associated disorders.
Cell death is important for many pathophysiological processes. However, uncontrolled cell death can lead to chronic inflammation and autoimmunity. Cell death-induced inflammation is also associated with cancer. Different cell death programs release specific factors that impact on immune responses and tumorigenesis in a distinctive manner. Our goal is to study the impact of different forms of programmed cell death on disease pathogenesis and to exploit this therapeutically by controlling the levels of cell death and by rewiring cell death programs to the host’s advantage.
Our goal is to study the impact of different forms of programmed cell death on disease pathogenesis and to exploit this therapeutically by controlling the levels of cell death and by rewiring cell death programs to the host’s advantage.
We showed that not only necroptosis, but also apoptosis can induce inflammation. This discovery challenges the current understanding of apoptosis as an immunologically silent mode of cell death. Recently, we discovered that LUBAC has a prominent role in regulating metabolic dysfunction during obesity and ageing.
We aim to study the mechanisms dictating β-cell death in the context of autoimmunity and during obesity, and find common and unique features in T1/2D. Furthermore, we aim to explore the interplay between cell death and obesity-induced inflammation and to understand the contribution of adipocyte death during obesity in metabolic syndromes (including T2D) and in the tumor microenvironment (Fig. 3). Our mission is to understand disease aetiology at the molecular level to identify potential treatments for autoimmune and inflammation-driven disorders, including cancer.
TNFR1 activation, the best characterized immune receptor, results in downstream events that cause: i) inflammation/survival via NF-kB/MAPK ii) apoptosis, or pyroptosis, via FADD/RIPK1/Casp-8 or, iii) necroptosis via RIPK1/RIPK3 and MLKL. In normal physiology, TNFR1-signalling output is skewed towards inflammation/survival; however, in pathological conditions this balance is shifted towards cell death induction.
Principal Investigator