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

 

102. Sereesongsaeng, N., J.F. Burrows, C.J. Scott, K. Brix, and R.E. Burden (2023) Cathepsin V regulates cell cycle progression and histone stability in the nucleus of breast cancer cells. Front. Pharmacol. 14, 1271435. https://doi.org/10.3389/fphar.2023.1271435.

101. Chen, Y. A. Barba-Bon, B. Grüner, M. Winterhalter, M.A. Aksoyoglu, S. Pangeni, M. Ashjari, K. Brix, G. Salluce, Y. Folgar-Camean, J. Montenegro, and W.M. Nau (2023) Metallacarborane Cluster Anions of the Cobalt Bisdicarbollide-Type as Chaotropic Carriers for Transmembrane and Intracellular Delivery of Cationic Peptides. J. Am. Chem. Soc. 145, 13089-13098. https://doi.org/10.1021/jacs.3c01623.

100. Dogru, A.G., M. Rehders, and K. Brix (2023) Investigations on primary cilia of Nthy-ori 3-1 cells upon cysteine cathepsin inhibition or thyrotropin stimulation. Int. J. Mol. Sci. 24, 9292. https://doi.org/10.3390/ijms24119292.

99. Venugopalan, V., M. Rehders, J. Weber, L. Rodermund, A. Al-Hashimi, T. Bargmann, J. Golchert, V. Reinecke, G. Homuth, U. Völker, F. Verrey, J. Kirstein, H. Heuer, U. Schweizer, D. Braun, E.K. Wirth, and K. Brix (2022) Lack of L-type amino acid transporter 2 in murine thyroid tissue induces autophagy. J. Mol. Endocrinol. 2022 Dec 7;70(1): e220060. https://doi.org/10.1530/JME-22-0060.

98. Yu, D.M.T. / Dauth, S., M.B. Margineanu, V. Snetkova, M. Rehders, S. Jordans, and K. Brix (2022) Characterization of cysteine cathepsin expression in the central nervous system of aged wild-type and cathepsin-deficient mice. Appl. Sci. 12, 2608. https://doi.org/10.3390/app12052608.

97. Tamhane, T., R.W. Njenga, R.E. Burden, H. Büth, G.M. Maelandsmo, M.H. Haugen, C.J. Scott, and K. Brix (2021) Trafficking of Full-Length and N-Terminally Truncated Cathepsin B in Human Colorectal Carcinoma Cells. Appl. Sci. 11, 11936. https://doi.org/10.3390/app112411936.

96. Kerp, H., K. Renko, G.S. Hönes, K. Brix, J. Köhrle, L.C. Moeller, and D. Führer (2021) Age-dependent response to T4 overtreatment and recovery on systemic and organ level. J. Mol. Endocrinol. 67, 161-172. https://doi.org/10.1530/JME-21-0109.

95. Qatato, M., V. Venugopalan, A. Al-Hashimi, M. Rehders, A.D. Valentine, Z. Hein, U. Dallto, S. Springer, and K. Brix (2021) Trace Amine-Associated Receptor 1 Trafficking to Cilia of Thyroid Epithelial Cells. Cells 10, 1518. https://doi.org/10.3390/cells10061518.

94. Venugopalan, V., Al-Hashimi, A., Weber, J., Rehders, M., Qatato, M., Wirth, E.K., Schweizer, U., Heuer, H., Verrey, F., and K. Brix (2021b) The Amino Acid Transporter Mct10/Tat1 Is Important to Maintain the TSH Receptor at Its Canonical Basolateral Localization and Assures Regular Turnover of Thyroid Follicle Cells in Male Mice. Int. J. Mol. Sci. 22, 5776. https://doi.org/10.3390/ijms22115776.

93. Kunath, A., J. Weiner, K. Krause, M. Rehders, A. Pejkovska, M. Gericke, M.L. Biniossek, S. Dommel, M. Kern, A. Ribas-Latre, O. Schilling, K. Brix, M. Stumvoll, N. Klöting, and J.T. Heiker / M. Blüher (2021) Role of Kallikrein 7 in Body Weight and Fat Mass Regulation. Biomedicines 9, 31. https://doi.org/10.3390/biomedicines9020131.

92. Venugopalan, V., A. Al-Hashimi, M. Rehders, J. Golchert, V. Reinecke, G. Homuth, U. Völker, M. Manirajah, A. Touzani, J. Weber, M.S. Bogyo, F. Verrey, E.K. Wirth, U. Schweizer, H. Heuer, J. Kirstein, and K. Brix (2021a) The Thyroid Hormone Transporter Mct8 Restricts Cathepsin-Mediated Thyroglobulin Processing in Male Mice through Thyroid Auto-Regulatory Mechanisms that Encompass Autophagy. Int. J. Mol. Sci. 22, 462. https://doi.org/10.3390/ijms22010462.

91. Ziros, P.G., C.O. Renaud, D.V. Chartoumpekis, M. Bongiovanni, I.G. Habeos, X.-H. Liao, S. Refetoff, P.A. Kopp, K. Brix, and G.P. Sykiotis (2021) Mice hypomorphic for Keap1, a negative regulator of the Nrf2 antioxidant response, show age-dependent diffuse goiter with elevated thyrotropin levels. Thyroid 31, 23-35. Received 17 Jan 2020 / Accepted: 9 July 2020. https://doi.org/10.1089/thy.2020.0044.

90. Al-Hashimi, A., V. Venugopalan, M. Rehders, N. Sereesongsaeng, Z. Hein, S. Springer, E. Weber, D. Führer, M.S. Bogyo, C.J. Scott, R.E. Burden, and K. Brix (2020b) Procathepsin V is secreted in a TSH regulated manner from human thyroid epithelial cells and is accessible to an activity-based probe. Int. J. Mol. Sci. 21(23), 9140. https://doi.org/10.3390/ijms21239140.

89. Al-Hashimi, A., V. Venugopalan, N. Sereesongsaeng, S. Tedelind, A.M. Pinzaru, Z. Hein, S. Springer, E. Weber, D. Führer, C.J. Scott, R.E. Burden, and K. Brix (2020a) Significance of nuclear cathepsin V in normal thyroid epithelial and carcinoma cells. BBA – Molecular Cell Research 1867, 118846. ShareLink: https://authors.elsevier.com/a/1blp8c5IDcJ7S. https://doi.org/10.1016/j.bbamcr.2020.118846.

88. Falkowski, K., E. Bielecka, I.B. Thøgersen, O. Bochenska, K. Płaza, M. Kalinska, L. Sasiadek, M. Magoch, A. Pecak, M. Wisniewska, N. Gruba, M. Wysocka, A. Wojtysiak, M. Brzezinska-Bodal, K. Sychowska, A. Pejkovska, M. Rehders, G. Butler, C.M. Overall, K. Brix, G. Dubin, A. Lesner, A. Kozik, J.J. Enghild, J. Potempa, and T. Kantyka (2020) Kallikrein-Related Peptidase 14 Activates Zymogens of Membrane Type Matrix Metalloproteinases (MT-MMPs) — A CleavEx Based Analysis. Int. J. Mol. Sci. 21(12), 4383. https://doi.org/10.3390/ijms21124383.

87. Biebermann, H. / K. Brix / D. Führer (2020) Seven Years of Active Thyroid Hormone Research in Germany: Thyroid Hormone Action beyond Classical Concepts. Exp. Clin. Endocrinol. Diabetes 128(6-07), 355-357. https://doi.org/10.1055/a-1163-7355.

86. Brix, K., J. Szumska, J. Weber, M. Qatato, V. Venugopalan, A. Al-Hashimi, and M. Rehders (2020) Auto-regulation of the thyroid gland beyond classical pathways. Exp. Clin. Endocrinol. Diabetes 128(6-07), 437-445. https://doi.org/10.1055/a-1080-2969.

85. Dauth, S., H. Rakov, R.F. Sirbulescu, I. Ilies, J. Weber, B. Batbajar Dugershaw, D. Braun, M. Rehders, E.K. Wirth, D. Führer, U. Schweizer, and K. Brix (2020) Function of cathepsin K in the central nervous system of male mice is independent of its role in the thyroid gland. Cell. Mol. Neurobiol. 40, 695-710. https://doi.org/10.1007/s10571-019-00765-6.

84. Szumska, J., Z. Batool, A. Al-Hashimi / V. Venugopalan / V. Skripnik, N. Schaschke, M. Bogyo, and K. Brix (2019) Treatment of rat thyrocytes in vitro with cathepsin B and L inhibitors results in disruption of primary cilia leading to redistribution of the trace amine associated receptor 1 to the endoplasmic reticulum. Biochimie 166, 270-285. https://doi.org/10.1016/j.biochi.2019.07.010.

83. Brix, K. / H. Biebermann / D. Führer (2019) Priority program „Thyroid Trans Act“ (SPP1629) of the German Research Foundation – New Aspects in Thyroid Research. Nuklearmediziner 42, 1-5

82. Gruba, N. / E. Bielecka, M. Wysocka, A. Wojtysiak, M. Brzezińska-Bodal, K. Sychowska, M. Kalińska, M. Magoch, A. Pęcak, K. Falkowski, M. Wiśniewska, L. Sąsiadek, K. Płaza, E. Kroll, A. Pejkovska, M. Rehders, K. Brix, G. Dubin, T. Kantyka, and J. Potempa / A. Lesner (2019) Development of chemical tools to monitor human kallikrein 13 (KLK13) activity. Int. J. Mol. Sci. 20(7). pii: E1557. https://doi.org/10.3390/ijms20071557.

81. Engels, K. / H. Rakov, G.S. Hönes, K. Brix, J. Köhrle, D. Zwanziger, L.C. Moeller, and D. Führer (2019) Aging alters phenotypic traits of thyroid dysfunction in male mice with divergent effects on complex systems but preserved thyroid hormone action in target organs. J. Gerontol. A Biol. Sci. Med. Sci. pii: glz040. https://doi.org/10.1093/gerona/glz040

80. Qatato, M. / J. Szumska, V. Skripnik, E. Rijntjes, J. Köhrle, and K. Brix (2018). Canonical TSH Regulation of Cathepsin-Mediated Thyroglobulin Processing in the Thyroid Gland of Male Mice Requires Taar1 Expression. Front. Pharmacol. 9:221. https://doi.org/10.3389/fphar.2018.00221.

79. Fischer, J., C. Rutz, D. Zwanziger, N. Khajavi, A. Müller, M. Rehders, K. Brix, C.L. Worth, D. Führer, H. Krude, B. Wiesner, and R. Schülein / H. Biebermann (2018). Evidence of G-protein coupled receptor and substrate transporter heteromerization at a single molecule level. Cell. Mol. Life Sci. 75, 2227-2239, https://doi.org/10.1007/s00018-017-2728-1.

78. Rakov, H., K. Engels, G.S. Hönes, K. Brix, J. Köhrle, L.C. Moeller, D. Zwanziger, and D. Führer (2017). Sex-specific phenotypes of hyperthyroidism and hypothyroidism in aged mice. Biology of Sex Differences 8, 38. https://doi.org/10.1186/s13293-017-0159-1.

77. Oettmeier, C., K. Brix, and H.-G. Döbereiner (2017). Topical Review: Physarum polycephalum – a new take on a classic model system. J. Phys. D: Appl. Phys. 50, no. 41. https://doi.org/10.1088/1361-6463/aa8699.

76. Couture, F., A.M. Jansen, P. Taghert, and K. Brix (2017). EJCB - Molecular basis of protein fates in the secretory and endocytic pathways, and beyond. Eur. J. Cell Biol. 96, 369–371. https://doi.org/10.1016/j.ejcb.2017.06.006

75. Badziong, J., S. Ting, S. Synoracki, V. Tiedje, K. Brix, G. Brabant, L.C. Moeller, K.W. Schmid, D. Führer, and D. Zwanziger (2017). Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism. Eur. J. Endocrinol. 177, 243-250. https://doi.org/10.1530/EJE-17-0279

74. Hakeem Said, I.H., A. Rezk, I. Hussain, A. Grimbs, A. Shrestha, H. Schepker, K. Brix, M.S. Ullrich, and N. Kuhnert (2017). Metabolome comparison of bioactive and inactive Rhododendron extracts and identification of an antibacterial cannabinoid(s) from Rhododendron collettianum. Phytochem. Anal. 28, 454–464. https://doi.org/10.1002/pca.2694

73. Grimbs, A., A. Shrestha, A.S.D. Rezk, S. Grimbs, I. Hakeem Said, H. Schepker, M.-T. Hütt, D.C. Albach, K. Brix, N. Kuhnert, and M.S. Ullrich (2017). Bioactivity in Rhododendron: A systemic analysis of antimicrobial and cytotoxic activities and their phylogenetic and phytochemical origins. Frontiers in Plant Science, 8, Article 551. https://doi.org/10.3389/fpls.2017.00551

72. Weber, J., J. McInnes, C. Kizilirmak, M. Rehders, M. Qatato, E.K. Wirth, U. Schweizer, F. Verrey, H. Heuer, and K. Brix (2017). Interdependence of thyroglobulin processing and thyroid hormone export in the mouse thyroid gland. Eur. J. Cell Biol. 96, 440-456. https://doi.org/10.1016/j.ejcb.2017.02.002

71. Engels, K. / H. Rakov, D. Zwanziger, S.G. Hoenes, M. Rehders, K. Brix, J. Köhrle, L.C. Moeller, D. Führer (2016). Efficacy of protocols for induction of chronic hyperthyroidism in male and female mice. Endocrine 54, 47-54. https://doi.org/10.1007/s12020-016-1020-8

70. Elsadig Karar, M.G., L. Quiet, A. Rezk, R. Jaiswal, M. Rehders, M.S. Ullrich, K. Brix, and N. Kuhnert (2016). Phenolic profile and in vitro assessment of cytotoxicity and antibacterial activity of Ziziphus spina-christi leaf extracts. Med. Chem. (Los Angeles) 6, 143-156. https://doi.org/10.4172/2161-0444.1000339

69. Tamhane, T., R. Illukkumbura, S. Lu, G.M. Maelandsmo, M.H. Haugen, and K. Brix (2016). Nuclear cathepsin L activity is required for cell cycle progression of colorectal carcinoma cells. Biochimie 122, 208-218. https://doi.org/10.1016/j.biochi.2015.09.003

68. Tamhane, T., B.K. Wolters, R. Illukkumbura, G.M. Maelandsmo, M.H. Haugen, and K. Brix (2015). Construction of a plasmid coding for green fluorescent protein tagged cathepsin L and data on expression in colorectal carcinoma cells. Data in Brief 5, 468-475. https://doi.org/10.1016/j.dib.2015.09.022

67. Rezk, A., A. Al-Hashimi, W. John, H. Schepker, M.S. Ullrich, and K. Brix (2015b). Assessment of cytotoxicity exerted by leaf extracts from plants of the genus Rhododendron towards epidermal keratinocytes and intestine epithelial cells. BMC Complement Altern Med. 15:364. https://doi.org/10.1186/s12906-015-0860-8

66. Szumska, J., M. Qatato, M. Rehders, D. Führer, H. Biebermann, D.K. Grandy, J. Köhrle, and K. Brix (2015). Trace amine-associated receptor 1 localization at the apical plasma membrane domain of Fisher rat thyroid epithelial cells is confined to cilia. Eur. Thyroid J. 4 (Suppl. 1), 30-41. https://doi.org/10.1159/000434717

65. Führer, D. / K. Brix / H. Biebermann (2015). Understanding the healthy thyroid state in 2015. Eur. Thyroid J. 4 (Suppl. 1), 1-8. https://doi.org/10.1159/000431318

64. Brix, K., J. McInnes, A. Al-Hashimi, M. Rehders, T. Tamhane, M.H. Haugen (2015). Proteolysis mediated by cysteine cathepsins and legumain - recent advances and cell biological challenges. Protoplasma 252, 755-774. https://doi.org/10.1007/s00709-014-0730-0.

63. Rezk, A., J. Nolzen, H. Schepker, D.C. Albach, K. Brix, and M.S. Ullrich (2015a). Phylogenetic spectrum and analysis of antibacterial activities of leaf extracts from plants of the genus Rhododendron. BMC Complementary & Alternative Medicine 15:67. https://doi.org/10.1186/s12906-015-0596-5.

62. Engels, K. / H. Rakov, D. Zwanziger, L.C. Moeller, G. Homuth, J. Köhrle, K. Brix, and D. Führer (2015) Differences in mouse hepatic thyroid hormone transporter expression with age and hyperthyroidism. Eur. Thyroid J. 4 (Suppl. 1),81-86. https://doi.org/10.1159/000381020

61. Fischer, J., G. Kleinau, A. Müller, P. Kühnen, D. Zwanziger, A. Kinne, M. Rehders, L.C. Moeller, D. Führer, A. Grüters, H. Krude, K. Brix, and H. Biebermann (2015). Modulation of monocarboxylate transporter 8 oligomerization by specific pathogenic mutations. J. Mol. Endocrinol. 54, 39-50. https://doi.org/10.1530/JME-14-0272

60. Haugen, M.H., K. Boye, J.M. Nesland, S.J. Pettersen, E.V. Egeland, T. Tamhane, K. Brix, G.M. Maelandsmo, and K. Flatmark (2015).  High expression of the cysteine proteinase legumain in colorectal cancer - Implications for therapeutic targeting. Eur. J. Cancer 51, 9-17. https://doi.org/10.1016/j.ejca.2014.10.020.

59. Mühlhaus, J., J. Dinter, D. Nürnberg, M. Rehders, M. Depke, J. Golchert, G. Homuth, C.-X. Yi, S. Morin, J. Köhrle, K. Brix, M. Tschöp, G. Kleinau, H. Biebermann (2014). Analysis of Human TAAR8 and Murine Taar8b Mediated Signaling Pathways and Expression Profile. Int. J. Mol. Sci. 15, 20638-20655. https://doi.org/10.3390/ijms151120638

58. Tamhane, T. / M. Arampatzidou, V. Gerganova, M. Tacke, R. Illukkumbura, S. Dauth, N. Schaschke, C. Peters, T. Reinheckel, and K. Brix (2014). The activity and localization patterns of cathepsins B and X in cells of the mouse gastrointestinal tract differ along its length. Biol. Chem. 395, 1201-1219. https://doi.org/10.1515/hsz-2014-0151

57. Führer, D. / K. Brix / H. Biebermann (2014). Übersicht / Review article: Schilddrüsenhormonwirkung – jenseits klassischer Konzepte. Das Schwerpunktprogramm „THYROID TRANS ACT“ (SPP1629) der Deutschen Forschungsgemeinschaft. Thyroid hormone action beyond classical concepts. The priority programme „THYROID TRANS ACT“ (SPP1629) of the German Research Foundation. Dtsch. Med. Wochenschr. 139, 492-496. https://doi.org/10.1055/s-0034-1369822

56. Müller, S., A. Faulhaber, C. Sieber, D. Pfeifer, T. Hochberg, M. Gansz, S.D. Deshmukh, S. Dauth, K. Brix, P. Saftig, C. Peters, P. Henneke, and T. Reinheckel (2014). The endolysosomal cysteine cathepsins L and K are involved in macrophage-mediated clearance of Staphylococcus aureus and the concomitant cytokine induction. FASEB J. 28, 162-175. https://doi.org/10.1096/fj.13-232272.

55. McInnes, J., M. Rehders, J.R. McFaline-Figueroa, K. Brix, L.A. Pon, and E. Nevoigt (2013). Defects in mitochondrial distribution during the prolonged lag phase of Saccharomyces cerevisiae preceding growth in glycerol as the sole source of carbon. FEMS Yeast Res. 13, 706-710. https://doi.org/10.1111/1567-1364.

54. Haugen, M.H., H.T. Johansen, S.J. Pettersen, R. Solberg, K. Brix, K. Flatmark, and G.M. Maelandsmo (2013). Nuclear legumain activity in colorectal cancer. PLoS One 8(1), e52980. https://doi.org/10.1371/journal.pone.0052980

53. Arampatzidou, M., A. Schütte, G.C. Hansson, P. Saftig, and K. Brix (2012). Effects of cathepsin K deficiency on intercellular junction proteins, luminal mucus layers, and extracellular matrix constituents in the mouse colon. Biol. Chem. 393, 1391-1403. https://doi.org/10.1515/hsz-2012-0204

52. Dauth, S. / M.M. Schmidt, M. Rehders, F. Dietz, S. Kelm, and R. Dringen / K. Brix (2012). Characterization and metabolism of astroglia-rich primary cultures from cathepsin K-deficient mice. Biol. Chem. 393, 959-970. https://doi.org/10.1515/hsz-2012-0145

51. Arampatzidou, M., K. Mayer, M.E. Iolyeva, S. Gebre Asrat, M. Ravichandran, T. Günther, R. Schüle, T. Reinheckel, and K. Brix (2011). Studies of intestinal morphology and cathepsin B expressing in a transgenic mouse aiming at intestine-specific expression of Cath B-EGFP. Biol. Chem. 392, 983-993. https://doi.org/10.1515/BC.2011.096

50. Dauth, S., R.F. Sirbulescu, S. Jordans, M. Rehders, L. Avena, J. Oswald, A. Lerchl, P. Saftig, and K. Brix (2011). Cathepsin K deficiency in mice induces structural and metabolic changes in the central nervous system that are associated with learning and memory deficits. BMC Neuroscience 12, 74. https://doi.org/10.1186/1471-2202-12-74

49. Brix, K. / D. Führer / H. Biebermann (2011). Molecules important for thyroid hormone synthesis and action – known facts and future perspectives. Thyroid Research 4 (Suppl 1), S9. https://doi.org/10.1186/1756-6614-4-S1-S9

48. Tedelind, S., S. Jordans, H. Resemann, G. Blum, M. Bogyo, D. Führer, and K. Brix (2011). Cathepsin B trafficking in thyroid carcinoma cells. Thyroid Research 4 (Suppl 1), S2. https://doi.org/10.1186/1756-6614-4-S1-S2

47. Dauth, S., M. Arampatzidou, M. Rehders, D.M.T. Yu, D. Führer, and K. Brix (2011). Thyroid cathepsin K – roles in physiology and thyroid disease. Clin. Rev. Bone Miner. Metab. 9, 94-106. https://doi.org/10.1007/s12018-011-9093-7

46. Arampatzidou, M., M. Rehders, S. Dauth, D.M.T. Yu, S. Tedelind, and K. Brix (2011). Imaging of protease functions – current guide to spotting cysteine cathepsins in classical and novel scenes of action in mammalian epithelial cells and tissues. It. J. Anat. Embryol. 116, 1-19.

45. Rehders, M., B.B. Grosshäuser, A. Smarandache, A. Sadhukhan, U. Mirastschijski, J. Kempf, M. Dünne, K. Slenzka, and K. Brix (2011). Effects of lunar and mars dust simulants on HaCaT keratinocytes and CHO-K1 fibroblasts. Adv. Space Res. 47, 1200-1213. https://doi.org/10.1016/j.asr.2010.11.033

44. Tedelind, S., K. Poliakova, A. Valeta, R. Hunegnaw, E. Lemma Yemanaberhan, N.-E. Heldin, J. Kurebayashi, E. Weber, N. Kopitar-Jerala, B. Turk, M. Bogyo, and K. Brix (2010). Nuclear cysteine cathepsin variants in thyroid carcinoma cells. Biol. Chem. 391, 923-935. https://doi.org/10.1515/BC.2010.109.

43. Uzunova, V.D., C. Cullinane, K. Brix, W.M. Nau, and A.I. Day (2010). Toxicity of cucurbit[7]uril and cucurbit[8]uril: an exploratory in vitro and in vivo study. Org. Biomol. Chem. 8, 2037-2042. https://doi.org/10.1039/B925555A

42. Berger, M., A. Farcas, M. Geertz, P. Zhelyaszkova, K. Brix, A. Travers, and G. Muskhelishvili (2010). Coordination of genomic structure and transcription by the main bacterial nucleoid-associated protein HU. EMBO Reports 11, 59-64. https://doi.org/10.1038/embor.2009.232

41. Donfack, P., M. Rehders, K. Brix, P. Boukamp, and A. Materny (2010). Micro Raman spectroscopy for monitoring alterations between human skin keratinocytes HaCaT and their tumorigenic derivatives A5RT3 – toward a Raman characterization of a skin carcinoma model. J. Raman Spectrosc. 41, 16-26. https://doi.org/10.1002/jrs.2400

40. Jordans, S., S. Jenko-Kokalj, N.M. Kühl, S. Tedelind, W. Sendt, D. Brömme, D. Turk, and K. Brix (2009). Monitoring compartment-specific substrate cleavage by cathepsins B, K, L, and S at physiological pH and redox conditions. BMC Biochemistry 10, 23. https://doi.org/10.1186/1471-2091-10-23

39. Vreemann, A., H. Qu, K. Mayer, L. Bjorkholt Andersen, M.I. Stefana, S. Wehner, M. Lysson, A.M. Farcas, C. Peters, T. Reinheckel, J. Kalff, and K. Brix (2009). Cathepsin B release from rodent intestine mucosa due to mechanical injury results in extracellular matrix damage in early post-traumatic phases. Biol. Chem. 390, 481-492. https://doi.org/10.1515/BC.2009.055

38. Mayer, K., A. Vreemann, H. Qu, and K. Brix (2009). Release of endo-lysosomal cathepsins B, D, and L from IEC6 cells in a cell culture model mimicking intestinal manipulation. Biol. Chem. 390, 471-480. https://doi.org/10.1515/BC.2009.047

37. Mayer, K., M.E. Iolyeva, U. Meyer-Grahle, and K. Brix (2008). Intestine-specific expression of green fluorescent protein-tagged cathepsin B: proof-of-principle experiments. Biol. Chem. 389, 1085-1096. https://doi.org/10.1515/BC.2008.360

36. Waldron, E., C. Heilig, A. Schweitzer, N. Nadella, S. Jaeger, A.M. Martin, S. Weggen, K. Brix, and C.U. Pietrzik (2008). LRP1 modulates APP trafficking along early compartments of the secretory pathway. Neurobiology of Disease 31, 188-197. https://doi.org/10.1016/J.nbd.2008.04.006

35. Brix, K., A. Dunkhorst, K. Mayer, and S. Jordans (2008). Cysteine cathepsins: Cellular roadmap to different functions. Biochimie 90, 194-207. https://doi.org/10.1016/j.biochi.2007.07.024

34. Kubica, M., K. Guzik, J. Koziel, M. Zarebski, W. Richter, B. Gajkowska, A. Golda, A. Maciag-Gudowska, K. Brix, L. Shaw, T. Foster, and J. Potempa (2008). A potential new pathway for Staphylococcus aureus dissemination: The silent survival and intracellular proliferation of S. aureus phagocytosed by human monocyte-derived macrophages. PLoS ONE 3, e1409. https://doi.org/10.1371/journal.pone.0001409

33. Ong, P.C., S. McGowan, M.C. Pearce, J.A. Irving, W.-T.Kan, S.A. Grigoryev, B. Turk, G.A. Silverman, K. Brix, S.P. Bottomley, and J.C. Whisstock, R. Pike (2007). DNA accelerates the inhibition of human cathepsin V by serpins. J. Biol. Chem. 282, 36980-36986.  https://doi.org/10.1074/jbc.M706991200

32. Büth, H., P.L. Buttigieg, R. Ostafe, M. Rehders, S.R. Dannenmann, N. Schaschke, H.-J. Stark, P. Boukamp, and K. Brix (2007). Cathepsin B is essential for regeneration of scratch-wounded normal human epidermal keratinocytes. Eur. J. Cell Biol. 86, 747-76. https://doi.org/10.1016/j.ejcb.2007.03.009

31. Brix, K., and S. Jordans (2005). News & Views: Watching proteases in action. Nat. Chem. Biol. 1, 186-187. https://doi.org/10.1038/nchembio0905-186.

30. Büth, H., B. Wolters, B. Hartwig, R. Meier-Bornheim, H. Veith, M. Hansen, C.P. Sommerhoff, N. Schaschke, W. Machleidt, N.E. Fusenig, P. Boukamp, and K. Brix (2004). HaCaT keratinocytes secrete lysosomal cysteine proteinases during migration. Eur. J. Cell Biol. 83, 781-795.

29. Friedrichs, B., C. Tepel, Th. Reinheckel, J. Deussing, K. von Figura, V. Herzog, Ch. Peters, P. Saftig, and K. Brix (2003). Thyroid functions of mouse cathepsins B, K, and L. J. Clin. Invest. 111, 1733-1745

28. Novak, N., C. Tepel, S. Koch, K. Brix, Th. Bieber, and St. Kraft (2003). Evidence for a differential expression of the FceRIg chain in dendritic cells of atopic and nonatopic donors. J. Clin. Invest. 111, 1047-1056.

27. Linke, M., V. Herzog, and K. Brix (2002). Trafficking of lysosomal cathepsin B – green fluorescent protein to the surface of thyroid epithelial cells involves the endosomal/lysosomal compartment. J. Cell Sci. 115, 4877-4889.

26. Linke, M., S. Jordans, L. Mach, V. Herzog, and K. Brix (2002). Thyroid stimulating hormone upregulates secretion of cathepsin B from thyroid epithelial cells. Biol. Chem. 383, 773-784.

25. Krüger, O., J.L. Beny, F. Chabaud, O. Traub, M. Theis, K. Brix, S. Kirchhoff, and K. Willecke (2002). Altered dye diffusion and upregulation of connexin37 in mouse aortic endothelium deficient in connexin40. J. Vasc. Res. 39, 160-172.

24. Brix, K., M. Linke, C. Tepel, and V. Herzog (2001). Cysteine proteinases mediate extracellular prohormone processing in the thyroid. Biol. Chem. 382, 717-725.

23. Hitzel, C., H. Kanzler, A. König, M.P. Kummer, K. Brix, V. Herzog, and N. Koch (2000). Thyroglobulin type I-like domains in invariant chain fusion proteins mediate resistance to cathepsin L digestion. FEBS Lett. 485, 67-70.

22. Tepel, C., D. Brömme, V. Herzog, and K. Brix (2000). Cathepsin K in thyroid epithelial cells: Sequence, localization, and possible function in extracellular proteolysis of thyroglobulin. J. Cell Sci. 113, 4487-4498.

21. Saber-Lichtenberg, Y., K. Brix, A. Schmitz, J.E. Heuser, J.H. Wilson, L. Lorand, and V. Herzog (2000). Covalent cross-linking of secreted bovine thyroglobulin by transglutaminase. FASEB J. 14, 1005-1014.

20. Dombrowski, F., L. Klotz, H.J. Hacker, Y. Li, D. Klingmüller, K. Brix, V. Herzog, and P. Bannasch (2000). Hyperproliferative hepatocellular alterations after intraportal transplantation of thyroid follicles. Am. J. Pathol. 156, 99-113.

19. Lemansky, P., K. Brix, and V. Herzog (1999). Subcellular distribution, secretion and posttranslational modifications of clusterin in thyrocytes. Exp. Cell Res. 251, 147-155.

18. Brix, K., W. Summa, F. Lottspeich, and V. Herzog (1998). Extracellularly occuring histone H1 mediates the binding of thyroglobulin to the cell surface of mouse macrophages. J. Clin. Invest. 102, 283-293.

17. Lemansky, P., K. Brix, and V. Herzog (1998). Iodination of mature cathepsin D in thyrocytes as an indicator for its transport to the cell surface. Eur. J. Cell Biol. 76, 53-62.

16. Brix, K., R. Wirtz, and V. Herzog (1997). Paracrine interaction between hepatocytes and macrophages after extrathyroidal proteolysis of thyroglobulin. Hepatology 26, 1232-1240.

15. Graebert, K.S., H. Bauch, W. Neumüller, K. Brix, and V. Herzog (1997). Epithelial folding in vitro: Studies on the cellular mechanism underlying evagination of thyrocyte monolayers. Exp. Cell Res. 231, 214-225.

14. Brix, K., P. Lemansky, and V. Herzog (1996). Evidence for extracellularly acting cathepsins mediating thyroid hormone liberation in thyroid epithelial cells. Endocrinology 137, 1963-1974.

13. Brix, K., and V. Herzog (1994). Extrathyroidal release of thyroid hormones from thyroglobulin by J774 mouse macrophages. J. Clin. Invest. 93, 1388-1396.

12. Stockem, W., and K. Brix (1994). Analysis of microfilament organization and contractile activities in Physarum. Int. Rev. Cytol. 149, 145-215.

11. Steffan, B., K. Brix, and W. Pütz (1993). Biosynthesis of Shermilamine B. Tetrahedron 49, 6223-6228.

10. Ohl, C., K. Brix, and W. Stockem (1991). Studies on microplasmodia of Physarum polycephalum. VIII. Quantitative analysis of contractile activities and microfilament organization. Cell Tissue Res. 264, 283-291.

9. Brix, K., A. Reinecke, and W. Stockem (1990). Dynamics of the cytoskeleton in Amoeba proteus. III. Influence of microinjected antibodies on the organization and function of the microfilament system. Eur. J. Cell Biol. 51, 279-284.

8. Sodeik, B., K. Brix, and W. Stockem (1989). Sequestration of microinjected molecular probes from the cytoplasm of Amoeba proteus. Europ. J. Protistol. 25, 75-84.

7. Christofidou-Solomidou, M., K. Brix, and W. Stockem (1989). Induced pinocytosis and cytoskeletal organization in Amoeba proteus - a combined fluorescence and electron microscopic study. Europ. J. Protistol. 24, 336-345.

6. Brix, K., and W. Stockem (1989). Functional analysis of actin fibrils in Physarum polycephalum. A morphological and quantitative study. Cell Tissue Res. 257, 115-122.

5. Kukulies, J., K. Brix, and W. Stockem (1987). Studies on microplasmodia of Physarum polycephalum. VI. Functional analysis of a cortical and fibrillar actin system by use of fluorescent-analog cytochemistry. Cell Tissue Res. 250, 125-134.

4. Brix, K., W. Stockem, and J. Kukulies (1987). Chemically induced changes in the morphology, dynamic activity and cytoskeletal organization of Physarum cell fragments. Cell Biol. Int. Rep. 11, 803-811.

3. Brix, K., J. Kukulies, and W. Stockem (1987). Studies on microplasmodia of Physarum polycephalum. V. Correlation of cell surface morphology, microfilament organization and motile activity. Protoplasma 137, 156-167.

2. Brix, K., and W. Stockem (1987). Studies on microplasmodia of Physarum polycephalum. VII. Adhesion-dependent changes in the organization of the fibrillar actin system. Cell Biol. Int. Rep. 11, 529-536.

1. Kukulies, J., K. Brix, and W. Stockem (1985). Fluorescent analog cytochemistry of the actin system and cell surface morphology in Physarum microplasmodia. Eur. J. Cell Biol. 39, 62-69.

 

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.