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Intracellular cytokine profile of T lymphocytes in patients with chronic obstructive pulmonary disease

During my MD-PhD, I led a project aimed at the in depth characterization of nintedanib, which is a relatively new anti-angiogenic small molecule tyrosine kinase inhibitor, in the Rip1Tag2 mouse model of pancreatic neuroendocrine tumors. We recently published this work in “Clinical Cancer Research” [380]. In addition, together with Laura Pisarsky, we were investigating mechanisms of resistance to anti-angiogenic tyrosine kinase inhibitors (nintedanib, sunitinib) in a mouse model of breast cancer and in the Rip1Tag2 model. The manuscript of the latter project has been submitted for publication. Furthermore, I was involved in a project that identified an immature B-cell population serving as a surrogate marker in order to monitor tumor angiogenesis and response to anti-angiogenic compounds in several mouse models of cancer [548]. Subsequent to these research articles, I wrote a book chapter describing our routinely used tumor angiogenesis assays in the Rip1Tag2 mouse model. This chapter will be part of an edition of the lab protocol series “Methods in Molecular Biology” on tumor angiogenesis assays.

Furthermore, I am currently investigating the impact of a yet unpublished TKI of focal adhesion kinase (BI853520) on primary tumor growth and the metastatic cascade in several breast cancer mouse models. However, this project is not yet mature enough to be included in the present thesis. Lately, I was involved in the preclinical validation of Rho-Kinase 1 and 2 (ROCK1/2) as a potential metastasis-inhibiting target (Meyer-Schaller et al., manuscript in preparation).

Additionally, I have summarized the current knowledge about the relevance of EMT in the process of breast cancer metastasis published in a review in “FEBS Letters” [358]. Based on discussions I had during the preparation of this review, I have significantly contributed to the design and initiation of a new project in the Christofori laboratory, which aims to decipher the role of EMT in metastasis in different preclinical breast cancer metastasis mouse models involving sophisticated lineage-tracing and fate-mapping approaches.

Last but not least, I was supervising three master students (2 medical and 1 biology student) and I was engaged in teaching of medical students at the Faculty of Medicine of the University of Basel: During four years, I was a tutor in “Problem oriented Tutorials”, gave students insights into biomedical research with animals in the context of laboratory visits during the “Wissenschaftsmonats” and I was giving workshops about “nutrition and cancer” on the “Thementag Ernährung”.

9.

Curriculum Vitae

Personal Information

Name Bill

First name Ruben Michael

Nationality Swiss

Date and Place of Birth 22.08.1985, Meiringen (Switzerland)

Status not married, 2 children (Leona *2012, Lilja *2015)

Contact Morillonstrasse 2

3007 Bern Switzerland

Tel: (+41) 78 663 67 91 E-mail: [email protected]

Education and Professional Training

Nov 2011- present MD-PhD studies in Medical-Biological Research

Department of Biomedicine University of Basel, Switzerland

Laboratory of Prof. Dr. Gerhard Christofori,

Dec 2011 Promotion to Dr. med.

University of Bern, Switzerland

Fall 2011 “Eidgenössisches Staatsexamen Humanmedizin”

Jul 2011 Master of Medicine

University of Bern, Switzerland Oct 2005- Jul 2011 Medical studies

University of Bern, Switzerland Jul 2008- Jan 2010 Medical thesis

Theodor Kocher Institute University of Bern, Switzerland

Thesis: The role of PSGL-1 in the immunopathogenesis of experimental autoimmune encephalomyelitis.

Jun 2005 Matura

Gymnasium Hofwil, Münchenbuchsee, Switzerland

2001- 2005 Gymnasium

Hofwil, Münchenbuchsee, Switzerland, “Talentförderungsklasse Sport”

Research Experience and Courses

April 2012 Felasa Course

Category B; LTK Module 1: Introductory course in Laboratory Animal Science

Nov 2010 Research internship in tumor biology

Department of Biomedicine University of Basel, Switzerland

Laboratory of Prof. Dr. Gerhard Christofori, Sept- Oct 2010 Research internship in neuro-oncology

University Hospital Zurich, Switzerland Laboratory of Prof. Dr. Michael Weller

Sept- Nov 2009 Research internship in immunology

Department of Pathology

Harvard Medical School, Boston, USA Laboratory of Prof. Dr. Ulrich von Andrian, Aug- Sept 2007 Research internship in neuro-immunology

Theodor Kocher Institute University of Bern, Switzerland

Laboratory of Prof. Dr. Britta Engelhardt,

Teaching

2012- present Supervision of master students

David Johansson, medical master student Stefanie Tiede, biology master student

Philip Schmassmann, medical master student

2012- 2015 Teaching of medical students at the Faculty of Medicine, University of Basel, Switzerland

- Problem oriented Tutorial (PoT) - “Thementag Ernährung”

- Laboratory visit

Oct 2007- Apr 2009 Teaching assistant in histology courses of first- and second- year medical students at the Faculty of Medicine, University of Bern, Switzerland

Oct- Dec 2007 Tutor of first- year medical students at the Faculty of Medicine, University of Bern, Switzerland

Conferences and Symposia

May 2015 Scientific Meeting of the Swiss national MD-PhD program

Basel, Switzerland (poster presentation)

Jan 2015 Keystone Symposium Integrating Biology and Tumor

Metabolism

Vancouver, Canada (poster presentation)

Sept 2014 Kinome III Meeting

Basel, Switzerland (poster presentation)

May 2014 ENBDC workshop

Methods in mammary gland biology and breast cancer Weggis, Switzerland (poster presentation)

March 2014 Keystone Symposium Tumor Metabolism

Whistler, Canada (poster presentation)

Oct 2013 MD/PhD-MSc Basel and Zurich joint Retreat

Monte Verità, Switzerland (poster presentation)

May 2013 European Cancer Center Meeting

Strasbourg, France (poster presentation)

Apr 2013 NCCR Molecular Oncology Concluding Symposium

Lausanne, Switzerland (poster presentation)

Feb 2013 Department of Biomedicine Basel PhD winter retreat

Hasliberg, Switzerland (oral presentation)

Jan 2013 Charles Rodolph Brupbacher Symposium

Zurich, Switzerland

Nov 2012 Scientific Meeting of the Swiss national MD-PhD program

Solothurn, Switzerland (poster presentation)

Jun 2012 International Vascular Biology Meeting 2012 Wiesbaden,

Germany (poster presentation)

May 2012 European Cancer Center Meeting

Freiburg i. B., Germany

Nov 2010 Day of Clinical Research 2010

Department of Clinical Research, University of Bern, Switzerland (poster presentation)

Jun 2009 Training course neuro-immunology within the COST action

Neurinfnet

University of Minho, Braga, Portugal (poster presentation)

Jun 2009 Researcher Meeting of the Swiss Multiple Sclerosis Society

Interlaken, Switzerland (poster presentation)

Memberships/Fellowships/Awards

2012 “1. Fakultätspreis” of the Faculty of Medicine, University of Bern, for the best Medical thesis

2012- 2014 MD-PhD Fellowship of the Swiss National Science Foundation (3 years)

2008- 2014 Member of the Swiss Students Foundation

(www.studienstiftung.ch)

Publication List

Bill R, Döring A, Deutsch U, Engelhardt B. 2010. PSGL-1 is dispensable for the development

of active experimental autoimmune encephalomyelitis in SJL/J mice. J Neuroimmunol. 2011.

Bill R, Christofori G. 2015. The relevance of EMT in breast cancer metastasis: Correlation or

causality? FEBS Letters. 2015. Review article.

Fagiani E, Bill R, Pisarsky L, Ivanek R, Rüegg C, Christofori G. An immature B cell population from peripheral blood serves as surrogate marker for monitoring tumor angiogenesis and anti-angiogenic therapy in mouse models. Angiogenesis. 2015.

Bill R*, Fagiani E*, Zumsteg A, Antoniadis H, Johansson D, Haefliger S, Albrecht I, Hilberg F,

Christofori G. Nintedanib is a highly effective therapeutic for neuroendocrine carcinoma of the pancreas (PNET) in the Rip1Tag2 transgenic mouse model. Clinical Cancer Research. 2015.

Pisarsky L*, Bill R*, Ernesta Fagiani, Ryan William Goosen, Jörg Hagmann, and Gerhard Christofori. Targeting metabolic symbiosis to overcome resistance to anti-angiogenic therapy. (submitted)

Bill R, Christofori G. The Rip1Tag2 mouse model. Book chapter in Tumor angiogenesis

assays, Methods in Molecular Biology, Springer (in preparation).

Bill R, Tiede S, Fagiani E, Meyer-Schaller N, Haefliger S, Schmassmann P, Christofori G.

Influence of the novel Focal Adhesion Kinase (FAK) Inhibitor BI853520 on breast cancer primary tumor growth and metastasis (in preparation).

10. Acknowledgements

First of all, I would like to thank Prof. Dr. Gerhard Christofori for giving me the great opportunity to perform my MD-PhD thesis in his laboratory. I appreciated his role as a “consultant” rather than simply being “the boss”, allowing us to realize that the success of our career lies in our own hands. The freedom to develop new ideas, experiments and even projects enabled us to evolve into independent scientist with a critical view on the research of others and our own. I am convinced that with his tremendous experience and international network, I can get significant advices when it comes to important decisions in my future career.

Secondly, I am grateful to the current and previous members of the Christofori laboratory for technical inputs, critical questions, discussions and fun moments. I thank Dr. Ernesta Fagiani and Laura Pisarsky for fruitful collaborations in my two main projects. In addition, special thanks go to Dr. Maren Diepenbruck, Dr. Lorenz Waldmeier, Dr. Nathalie Meyer-Schaller, Dr. Ryan Goosen and Dr. Robert Ivanek for significant technical support, manuscript revisions and scientific discussions.

What would I have done without Helena Antoniadis, Isabel Galm, Ursula Schmieder, Petra Schmidt, Miranda Brito, Roland Jost, Angelika Offinger, Erika Visscher, Manfred Sieber, Pascal Lorentz and the other members of the Mattenstrasse administrative, infrastructure, IT and animal house staff? Thank you very much!

I am further highly grateful for the help of the students I have supervised: David Johansson, Philipp Granacher, Stefanie Tiede and Philip Schmassmann. Many thanks also to the civil service guys who have supported our laboratory: Patrick Stillhard, Andrea Vettiger and Simon Häfliger.

Furthermore, I would like to thank the members of my PhD committee, Prof. Dr. Markus Affolter and Prof. Dr. Curzio Rüegg for helping to improve my projects.

Many thanks also to my family for their amazing support ever since.

Last but not least and most importantly, dear Claudia, thank you for your love, for taking care of so many things, for being a great mother and understanding when I was treating mice instead of spending time with the family on countless weekends. Leona and Lilja, your smiles often adjusted the focus to the important things in life.