BEAT IT team

Research interests:  Pathologies of the immune system represent a major threat to healthy aging because of their abundance and limited therapeutic options. In our group, we study molecular mechanisms that control cell survival and fate decisions in B lymphocytes and their progenitors, through genetic mouse models and in vitro culture systems. Since 2015 we have identified the integration of miRNAs in B cell survival and selection, with the miR-17-92 miRNAs playing key roles in promoting autoimmunity. A similar principle holds in the control of malignant B cell outgrowth and MYC-driven lymphoma cell fitness where the miR-17-92 target gene BIM takes center stage. Separate lines of work have revealed CHK1-mediated DNA damage control as key element of normal B cell development, germinal center B cell fitness and antibody-mediated immunity. Recent achievements include the identification and characterization of the epigenetic TET enzymes as critical regulators of B-cell lineage specification and optimal humoral immune responses. Additional new insights relate to the tumor suppressor functions of TET2 operating in hematopoietic progenitors and B lymphocytes.

Other BEAT IT members: Sarah Spöck (PhD candidate)

Website:Experimental immunology lab (Medical University of Innsbruck)

Research interests: Our research focuses on the bioinformatic analysis of multimodal tumor data, and on the development of computational methods to guide and advance precision and personalized medicine. Our group has a special focus on cancer immunology: we integrate bioinformatics, systems biology, and machine learning techniques to shed light on the rules governing tumor-immune cell interactions. By characterizing the landscape of cancer neoantigens, the composition of the tumor immune contexture, and the intricate crosstalk governing cell-cell interactions in the tumor microenvironment, we aim at extracting mechanistic rationale to improve cancer therapy.

Other BEAT IT members: Irene Rigato (PhD candidate), Lorenzo Merotto (PhD candidate), Felix Petschko (PhD candidate)

Website:Computational Biomedicine lab (University of Innsbruck)

Research interests:  We aim to understand how cell death is inflammatory and use this knowledge to better treat human diseases. Cell death usually does not provoke an immune response. Due to their bacterial origins, mitochondria possess their own genome called mitochondrial (mt)DNA. Our bodies react to this in a similar way to “foreign” bacteria, and mount a rapid response to warn surrounding cells. Using super-resolution microscopy, we found that mtDNA can be released from mitochondria during cell death, invoking this immune response. Understanding this process could help to develop better treatments for cancer, and could be the cause of some auto-inflammatory diseases. The usual outcome of cell death is complete destruction of the cell. We have shown that under conditions of sub-lethal stress the cell death machinery is only partially engaged and the cell stays alive (a process we called “minority MOMP”). However, the cell accumulates DNA damage and becomes genomically unstable, which can transform the cell into a cancer cell. We recently showed that mitochondrial dysfunction is the underlying basis of this process, since “unwell” mitochondria become more likely to undergo permeabilisation. Given that minority MOMP has roles in innate immunity and inflammation, as well as cancer, we can use these findings to modulate minority MOMP. Our Approach: we use existing methods to understand inflammatory cell death, and we are rapid adopters of new technologies and tools to answer biological questions.

Other BEAT IT members: Nadine Kinz (PhD candidate)

Website:Cell death and inflammation lab (Medical University of Innsbruck)

Research interests:  Within the Cell Death Signalling Lab run by division head Andreas Villunger, we currently explore the cross talk of the cell death and the cell cycle machinery. Thereby, we focus on understanding signaling events that define thresholds for cell death or survival after mitotic errors. Two aspects keep us busy. How are mitotic errors communicated to the BCL2 family network that controls mitochondrial apoptosis and how is p53, a major tumor suppressor, engaged in this context. Within these studies, we have recently shown that mitotic arrest drives BAX/BAK-mediated cell death by degradation of anti-apoptotic MCL1 and increased abundance of pro-apopotic BIM and NOXA (Figure 1). Following up this finding, we now interrogate who abundance of these proteins is controlled in mitotic cells.

Other BEAT IT members: Johannes Weiss (MD, PhD candidate) Paul Yannick Luca Petermann (PhD candidate)

Website: Cell death signalling lab (Medical University of Innsbruck)