Gruppe Kaufmann

Short Curriculum Vitae

Prof. Dr. THOMAS KAUFMANN, PhD

Date of Birth:  May 16, 1976

Nationality:  Swiss

Office Address:  Institute of Pharmacology
  Medical Faculty
  University of Bern
  Inselspital, INO-F
  3010 Bern, CH-Switzerland
  Email: thomas.kaufmann@pki.unibe.ch
  Tel: +41 (0)31 632 32 89

ACADEMIC DEGREES
2014 Associate Professor, Medical Faculty, University of Bern (CH)
2011 'Venia Docendi' (Habilitation) in Experimental Pharmacology, University of Bern (CH)
2003  PhD in Biochemistry, Institute of Biochemistry, University of Fribourg (CH)
2000  Diploma in Biochemistry, Institute of Biochemistry, University of Fribourg (CH)

CAREER HISTORY AND POSITIONS HELD
2013-  Principal Investigator (Dozent I), Institute of Pharmacology, University of Bern, Switzerland
2008-2013 SNSF Assistant Professor, Institute of Pharmacology, University of Bern, Switzerland
2004-2007 Postdoctoral research fellow with Prof Andreas Strasser, Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research (WEHI), Melbourne, Australia
2003-2004 Postdoctoral research fellow Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Germany
2000 - 2003 PhD-student with Prof Christoph Borner, Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Germany
1995-2000 Studies in Biochemistry, University of Fribourg, Switzerland

GRANTS, FELLOWSHIPS AND AWARDS
2014 - 2017 SNSF Project Grant (D-A-CH) 310030E-150805
2014 - 2017 SNSF Project Grant 31003A_149387
2013 - 2015 Swiss Cancer League Research Grant; KFS-3014-08-2012
2012 - 2014 3R Foundation Research Grant; 127-11
2012 – 2013 Prolongation SNSF Professorship, Swiss National Science Foundation; PP00P3_139190/1
2008 – 2012 SNSF Professorship, Swiss National Science Foundation; PP00A-119203
2011 Best Poster Award, 19th ECDO meeting, Sep 14-17 2011, Stockholm (SWE)
2009 Research grant from the ‘Novartis Foundation for Biological-Medical Research’, Novartis, Basel (CH)
2006 – 2007 Postdoctoral fellowship for advanced researchers, Swiss National Science Foundation; PA00A-111430
2006 Postdoctoral fellowship ‘Novartis Foundation, formerly Ciba-Geigy-Jubiläumsstiftung’ (Novartis, Switzerland)
2005/2006 Postdoctoral fellowship ‘Roche Research Foundation’ (Roche, Switzerland)
2004 – 2005 Postdoctoral fellowship for prospective researchers, Swiss National Science Foundation; PBFRA-104383
2004 ’Faculty Prize’, Faculty of Science, University of Fribourg (CH)
2000 ’Syngenta Crop Protection Monthey SA 2000’ prize

MEMBERSHIPS AND HONORARY POSTS
- Member of the World Allergy Organization (WAO) Special Committee on Eosinophils, Mast Cells & Basophils (since 2013)
- Editorial Board Member of peer-reviewed journals: Allergy, Cell Death and Disease, Frontiers in Molecular and Cellular Oncology
- Member of the expert committee 'Cell Biology' within the Graduate School for Cellular and Biomedical Sciences, University of Bern; since 2009
- Member of the following associations: Swiss Society for Allergology and Immunology (SAAI), since 2013; European Cell Death Organization (ECDO), since 2008; Swiss Society of Experimental Pharmacology (SSEP), since 2008; Swiss Society for Biochemistry (BIO), since 2000; Swiss Society for Cell Biology, Molecular Biology and Genetics (ZMG), since 2000

Our group is interested in the molecular mechanisms of programmed cell death (PCD), in particular apoptosis and necroptosis, and the link between cell death and innate immune signaling. A focus in the latter lies on myeloid cells, in particular granulocytes (neutrophils and basophils) and mast cells, which are central players of innate immunity. Apoptosis is recognized as the most relevant (patho-) physiological form of PCD, whereas the physiological role of necroptosis is less well understood. Given that apoptosis suppresses necroptosis, the latter is hypothesized to serve as backup, proinflammatory, PCD upon infection with pathogens that actively block apoptosis.

We observed that upon activation of death receptors (Fas/CD95 or TNF-R1) on the surface of neutrophils the outcome ranges from activation of the cells and production of proinflammatory cytokines to PCD by apoptosis or by necroptosis. This outcome is tightly regulated and - among others - depends on the so-called inhibitor of apoptosis (IAPs) family. Our ongoing projects in the lab identify the IAP member XIAP as an antagonist of necroptosis downstream of death receptors. Interestingly, XIAP, which was initially identified as an inhibitor of apoptotic caspases and also carries E3 ligase activity (RING domain), clearly has important functions beyond blocking caspases. Our data indicate that XIAP may act more upstream in death receptor signaling pathways than previously assumed; the exact molecular functions of XIAP’s E3 ligase activity are under investigation. Taken together, XIAP can be placed at the intersection of cell death and inflammation.

Granulocytes isolated from mice can only be obtained in low numbers, which makes biochemical analyses difficult, and – in the case of basophils – almost impossible. We have established a protocol to generate conditionally immortalized progenitor cells (“Hoxb8 cells”) that are committed to the macrophage/neutrophil- or the basophil lineages. Those cells can be differentiated in vitro into mature granulocytes in nearly unlimited numbers. An advantage of “Hoxb8” cells over primary granulocytes lies in the straightforward possibility of further genetic manipulation, such as overexpression of genes of interest reconstitution of gene deficient cells lines with particular mutants of that same gene. Regarding basophils and mast cells, we are interested how cytokines, such as IL-3, or binding of IgE and subsequent crosslinking of the high affinity IgE receptor by antigen, activate these cells, and if/how those stimuli increase cellular viability. On the other hand, selective killing of activated basophils or mast cells (or activated immune cells in general) is an intriguing concept to target immunological disorders, including allergies. Newly developed drugs aiming at inducing apoptosis in cancer cells (so called BH3-mimetics) are tested in our lab for their potential to kill activated leukocyte populations selectively.

Currently of great interest to our group is the pro-apoptotic family member BOK. BOK has raised much interest recently, as it is deleted in human cancers with surprisingly high frequency. Several cancer models with our newly developed Bok-deficient mouse strain are ongoing in our lab and in collaboration with others to test the potential tumour suppressor potential of Bok. Other BOK related projects focus on the molecular function of this still rather enigmatic protein. So far we have demonstrated that BOK is much more widely expressed than previously reported and, intriguingly, we found that although it has the potential to induce apoptosis when highly expressed, BOK localizes preferentially to the membranes of the ER and Golgi apparatus rather than to mitochondria. The subcellular localization of BOK correlates with its association with IP3 receptors (Ca2+ channels on the ER) and a deregulated ER stress response of Bok-deficient cells. Interestingly, BOK is prominently also found in nuclear fractions. We are currently testing the biophysical properties of recombinant BOK on artificial lipid vesicles and isolated organelles, the role of BOK at the ER/Golgi and the role of BOK in the nucleus, for which we hypothesize a role in the regulation of cellular proliferation.