Prof. Klaudia Brix

The Brix-group has a cell biological orientation and integrates itself into the research network provided by the Molecular Life Scientists and Chemists at Constructor University Bremen.

cilia +++ GPCRs +++ proteases of the thyroid gland (incl. cancer) +++ proteases of the central nervous system +++ proteases of the gastro-intestinal tract (incl. cancer) +++ plant-derived bioactive substances +++ quantitative cell biology for tissue profiling

Research Agenda

The main interest of our research group is on the significance of proteolysis in the brain and in epithelia like epidermis of the skin, intestinal mucosa, and the thyroid gland. We focus on cathepsins of the cysteine peptidase family and analyse their involvement in physiological versus pathological conditions using human and rodent cell lines and advanced cell-labelling techniques. Moreover, we work on hormonally regulated proteases, the kallikreins.

Our research group generated fluorescent protein-tagged proteases as tools to visualize the transport pathways of proteolytic enzymes in eukaryotic cells by live-cell imaging, and studied the function of cysteine cathepsins in systemic approaches comprising transgenic mouse models.

We are interested in understanding how proteases are important for ageing, cell migration during wound healing of the skin and in thyroid cancer.

The group has studied G-protein coupled receptors like the trace amine-associated receptors, their trafficking and significance for thyroid regulation, and we plan to analyze their signaling significance on primary cilia.

In 2020, we started to investigate cysteine cathepsin-mediated activation of the Spike protein of the SARS-CoV‑2 causing COVID-19; the focus of these projects is on thyroid epithelial cells, enterocytes and neurons.

Thus, the main research interests are in the field of

• biomedical significance of proteolysis in the CNS and in epithelial organs

• GPCR trafficking and significance for thyroid regulation

• SARS-CoV-2 Spike protein activation by cysteine cathepsins at primary cilia and microvilli of epithelial cells and neurons

Throughout our projects, we employ computational methods in order to make sense of microscopic images not only qualitatively, but also quantitatively.

Klaudia Brix is an expert in protease cell biology.  Her work specializes in understanding the roles of cathepsins and kallikreins in both normal physiology and disease, particularly with respect to trafficking pathways.  Her group looks into the significance of proteases for physiological thyroid function. The group focused more recently on rerouting of protease traffic in breast, colorectal and thyroid carcinomas.  The group is further interested in regulation of proteolysis and how this is connected to G-protein coupled receptor signaling.  After completing her undergraduate and postgraduate training at the University of Bonn, Klaudia took up her current position of Professor of Cell Biology at Constructor University (previously known as Jacobs University Bremen).  Her teaching activities comprise molecular cell biology, biomedicine, and chemical biology.  Klaudia Brix was Chair of the 2012 GRC on Proteolytic Enzymes and Their Inhibitors and of the 2018 GRC on Protein Processing, Trafficking, and Secretion.  Klaudia Brix was Co-Coordinator of the Germany-wide, DFG-funded priority program “Thyroid Trans Act” from 2012 to 2019.  She is currently a Member of the Core Group of the EU-COST action ProteoCure.

Qualifications and Career

University Education

1997                 Habilitation in Cell Biology, University of Bonn, Germany

1985 – 1987      Dissertation, Cell Biology with a minor in Organic Chemistry, University of Bonn, Germany; Supervisor: Prof. Dr. Wilhelm Stockem; Topic: Structure and Function of the microfilament system of cellular fragments of the acellular slime mold Physarum polycephalum

1978 – 1985      Studies in Biology, University of Bonn, Germany

Career

2006 – present  Full Professor of Cell Biology, Study Program Chair BCCB – Biochemistry and Cell Biology, School of Science, Constructor University (previously known as IUB and Jacobs University), Bremen, Germany; Research group leader, PI of KFO 115; Co-Coordinator and PI of SPP 1629

2002 – 2006     Associate Professor of Cell Biology, School of Science, Constructor University (then, IUB), Bremen, Germany; Research group leader, PI of FOR 367 and KFO 115

1998 – 2002    Assistant Professor, University of Bonn, Germany; Member of Research Focus “Molecular Biology and Cell Biology", Member and research group leader in the “Bonner Forum Biomedizin”, therein: Manager of the program to support young scientists in biomedical research, Scientific Supervisor of the Reference Center for Confocal Laser Scanning Microscopy, PI of SFB 284 (2000-2002); Supervision of 26 Diploma Students and 9 PhD Students

1998 – 2001      Acting Professor (C3 Substitute), University of Bonn, Germany; Vice Chair of the Institute of Cell Biology

1996 – 1997      Lise-Meitner-Fellow, University of Bonn, Germany; Habilitation stipend program of North Rhine-Westphalia, Germany

1989-1996        Postdoctoral Fellow, University of Bonn, Germany; PI of SFB 284

1989                 Postdoctoral Fellow, University of Düsseldorf, Germany; Cardiovascular Research Department

1987 – 1988      Postdoctoral Fellow, University of Bonn, Germany; Priority Program "Cytoskeleton"

Supervision / Mentoring / Responsibilities in Undergraduate and Graduate Programs

BSc / Fall 2002 –   Lectures, Practical Courses, and Bachelor of Science Theses Supervisor in the Undergraduate Majors "Biochemistry and Cell Biology" and “Medicinal Chemistry and Chemical Biology”; Program Representative from Fall 2003 and Program Coordinator from Fall 2006 to Spring 2014, Deputy SPC from Fall 2019 to Spring 2021, Study Program Chair from Fall 2021; Co-Initiator and Organisor of an Exchange Program with New York University, Medical School; major contributions to the curriculum reforms in the School of Engineering and Science 2008 and 2012 and to the accreditation in 2019/2020; University Studies Courses; co-proposer of the 3C-model before JU-wide adoption in AY 2015/16

MSc / 2002 – 2015 Representative of the Specialization Area "Cellular and Molecular Biology" in the Graduate Program "MoLife"; Lectures, Journal Clubs, and Supervision of Laboratory Rotations and Master of Science Theses of Graduate Students of the Life Sciences Program "MoLife"; Supervision and co-supervision of Master’s Students, 12 finished successfully with MSc in BioRec and MoLife

PhD / Fall 2002 –  Supervision and co-supervision of PhD-Students; 5 finished successfully with PhD in Cell Biology in 2006, one in 2009, two in 2012, two in 2014, one in 2015, one in 2017, one in 2018, and two in 2022; 15 in total

Visiting Fellows  Host of visiting Students from Denmark, Germany, Greece, Italy, Poland, Slovenia, and Switzerland since Fall 2002; external PhD-examiner for Universities in Africa, Australia and Europe since Fall 2002

      European Thyroid Association, 2020 – 2021, ETA Project COVID-19 grant 2020

      DFG, COVID-19 Focus Funding, 2020 - 2022

      HAORI Stiftung Bremen, 2020 – 2024, Neuronal cilia as potential viral entry sites

Book and eBook

Proteases: Structure and Function, Klaudia Brix & Walter Stöcker (Eds.), Springer-Verlag Wien 2013. http://www.springer.com/de/book/9783709108840#aboutBook, ISBN 978-3-7091-0884-0, ISBN 978-3-7091-0885-7 (eBook)., doi:10.1007/978-3-7091-0885-7

Chapter 1 – Protease Families, Evolution and Mechanism of Action. Neil D. Rawlings; Chapter 2 – Kinetics of the Interaction of Peptidases with Substrates and Modifiers. Antonio Baici, Marko Novinec, Brigita Lenarčič; Chapter 3 – Compartmentalization of Proteolysis. Klaudia Brix, Christopher J. Scott, Margarete M.S. Heck; Chapter 4 – Cathepsins: Getting in Shape for Lysosomal Proteolysis. Ann H. Erickson, Ciro Isidoro, Lukas Mach, John S. Mort; Chapter 5 – Limited and Degradative Proteolysis in the Context of Posttranslational Regulatory Networks: Current Technical and Conceptional Advances. Stefan Tholen, Maria Magdalena Koczorowska, Zon Weng Lai, Joern Dengjel, Oliver Schilling; Chapter 6 – Exploring Systemic Functions of Lysosomal Proteases: The Perspective of Genetically Modified Mouse Models. Martina Gansz, Ursula Kern, Christoph Peters, Thomas Reinheckel; Chapter 7 – Astacins: Proteases in Development and Tissue Differentiation. Walter Stöcker and F. Xavier Gomis-Rüth; Chapter 8 – Proteases in Death Pathways. Andreas Flütsch and Markus G. Grütter; Chapter 9 – ADAM Proteases in Physiology and Pathophysiology: Cleave to Function in Health or to Cause Disease. Joachim Grötzinger and Stefan Rose-John; Chapter 10 – Proteases in the Nervous System. Holger Cynis, Stefan F. Lichtenthaler, Leona Wagner, Hans-Ulrich Demuth; Chapter 11 – Proteases in the Mammalian Digestive System. S. Gaylen Bradley, Toni M. Antalis, Judith S. Bond; Chapter 12 – Calpains in Health and Disease. John Anagli, Kevin K.W. Wang, Yasuko Ono, Hiroyuki Sorimachi; Chapter 13 – Metalloproteinases in Cartilage Matrix Breakdown: The Roles in Rheumatoid Arthritis and Osteoarthritis. Hideaki Nagase and Gillian Murphy; Chapter 14 – MMP-Mediated Collagen Remodeling and Vessel Functions. Agnès Noel and Nor Eddine Sounni; Chapter 15 – Proteases in Cancer: Significance for Invasion and Metastasis. Bonnie F. Sloane, Karin List, Barbara Fingleton, Lynn Matrisian

Book Chapters

6. Brix, K., M. Qatato, J. Szumska, V. Venugopalan, M. Rehders (2019). Thyroglobulin storage, processing and degradation for thyroid hormone liberation. In: The Thyroid and Its Diseases, edited by Markus Luster, Leonidas Duntas, and Leonard Wartofsky. Springer International Publishing AG, part of Springer Nature 2019. https://doi.org/10.1007/978-3-319-72102-6_3

5. Kuhnert, N., I.H. Said, A. Shrestha, A. Rezk, A. Grimbs, J. Nolzen, H. Schepker, K. Brix, D. Albach, and M. Ullrich (2018). Section: Medicinal Chemistry, Chapter 10: Rhododendron Natural Products as Sources of Novel Antibiotics. In: Rhododendrons International, pp. 142-151.

4. Brix, K. (2018). Host cell proteases: cathepsins. In: Activation of Viruses by Host Proteases, edited by Eva Böttcher-Friebertshäuser, Wolfgang Garten, and Hans Dieter Klenk. Springer-Verlag. REVIEW. ISBN 978-3-319-75474-1.

3. Brix, K., C.J. Scott, M.M.S. Heck (2013) Compartmentalization of Proteolysis. In: Proteases: Structure and Function, edited by Klaudia Brix and Walter Stöcker, Springer-Verlag Wien.

2. Brix, K. (2005) Chapter 05: Lysosomal Proteases: Revival of the Sleeping Beauty. In: Lysosomes, edited by Paul Saftig, Eurekah.com. Landes Bioscience. www.eurekah.com/abstract.php?chapid=2255&bookid=129&catid=15

1. Stockem, W., J. Kukulies, and K. Brix (1987). Analysis of cytoplasmic actomyosin functions in Physarum polycephalum by fluorescent analog cytochemistry. Internationales Symposium an der Akademie der Wissenschaften, Mainz. In: Fortschritte der Zoologie, 34: Nature and Function of Cytoskeletal Proteins in Motility and Transport. K.-E. Wohlfarth-Bottermann editor. Gustav Fischer Verlag, Stuttgart. 25-30.