Dieter Bromme

Contact Information
Life Sciences Centre
#4.558 (Office) – , #4.540 (Lab) – 2350 Health Sciences Mall
Vancouver, BC, Canada V6T 1Z3
Tel 1-604-822-1787
Lab Tel 1-604–822–5531
Lab Tel 1-604–822–7655
Fax 1-604-822-7742
Email: dbromme@interchange.ubc.ca
Email: dbromme@dentistry.ubc.ca
Lab Website: http://www.dentistry.ubc.ca/research/bromme/

Current Positions

  • Associate Member, Biochemistry and Molecular Biology, Medicine.
  • Professor, Oral Biological and Medical Sciences, Dentistry.
  • Canada Research Chair in Proteases and Diseases.

Research Interests

Many human diseases are characterized by an excessive proteolytic degradation of proteins of the extracellular matrix (e.g., bone and cartilage diseases, atherosclerosis, destructive lung diseases, cancer) or by an inappropriate proteolytic processing of proteins leading to auto-immune diseases and disorders caused by regulatory defects. Our laboratory is leading in the identification of novel therapeutic targets among intracellular lysosomal proteases and is focused on the role of these proteases in the pathogenesis of rheumatoid arthritis, atherosclerosis and certain forms of immune disorders. Our aim is to understand the role of lysosomal proteases in health and disease which may lead to new therapeutic approaches to treat these illnesses. To achieve our objective, we exploit an interdisciplinary approach which includes methods of molecular biology, enzymology, crystallography, histology, animal models and a wide range of collaborations with clinical and biotech institutions.

Selected Publications

  1. Simon Law, Xin Du, Preety Panwar, Nicollette Honson, Tom Pfeifer, Michel Roberge, Dieter Brömme. (2019). Identificationof substrate-specific inhibitors of cathepsin Kthrough high-throughput screening. Biochem. J. provisionally accept.
  2. Boraschi-Diaz I, Mort JS, Brömme D, Senis YA, Mazharian A, Komarova SV. (2018). Collagen type I degradation fragments act through the collagen receptor LAIR-1 to provide a negative feedback for osteoclast formation. Bone. 117: 23-30.
  3. Galibert M, Wartenberg M, Lecaille F, Saidi A, Joulin-Giet A, Korkmaz B,Bromme D, Ausagne V, Delmas AF, Lalmanach G. (2018). Substrate-derived triazolo- and azapeptides as inhibitors of cathepsins K and S. European Journal of Medicinal Chemistry. 144: 201-210.
  4. Panwar P, Law S, Jamroz A, Azizi P, Zhang D, Ciufolini M, Brömme D. (2018). Tanshinones that selectively block the collagenase activity of cathepsin K provide a novel class of ectosteric antiresorptive agents for bone. British Journal of Pharmacology. 175(6): 902-923.
  5. Liu C, Wang L, Zhu R, Liu H, Ma R, Chen B, Li L, Guo Y, Jia Q, Shi S, Zhao D, Mo F, Zhao B, Niu J, Fu M, Orekhov AN, Brömme D, Gao S, Zhang D. (2018). Rehmanniae Radix Preparata suppresses bone loss and increases bone strength through interfering with canonical Wnt/β-catenin signaling pathway in OVX rats. Osteoporosis International.
  6. Pirapaharan DC, Søe K, Panwar P, Madsen JS, Bergmann ML, Overgaard M, Brömme D, Delaisse JM. (2018). A mild inhibition of cathepsin K paradoxically stimulates the resorptive activity of osteoclasts in culture. Calcified Tissue International [Epub ahead of print].
  7. Liu H, Zhu R, Liu C, Ma R, Wang L, Chen B, Li L, Niu J, Zhao D, Mo F, Fu M, Brömme D, Zhang D, Gao S. (2017). Evaluation of decalcification techniques for rat femurs using HE and immunohistochemical staining. BioMed Research International. 2017: Article ID 9050754.
  8. Law S, Panwar P, Li J, Aguda AH, Jamroz A, Guido RVC, Brömme D. (2017). A composite docking approach for the indentification and characterization of ectosteric inhibitor of cathepsin K. PLoS ONE. 12(10): e0186869.
  9. Panwar P, Xue L, Srivastava K, Søe K, Law S, Delaisse JM, Brömme D. (2017). An ectosteric inhibitor of cathepsin K inhibits bone resorption in ovariectomized mice. Journal of Bone and Mineral Research. [Epub ahead of print: July 26].
  10. Ma R, Wang L, Zhao B, Liu C, Liu H, Zhu R, Chen B, Li L, Zhao D, Mo F, Li Y, Niu J, Jiang G, Fu M, Bromme D, Gao S, Zhang D. (2017). Diabetes perturbs bone microarchitecture and bone strength through regulation of Sema3A/IGF-1/β-Catenin in rats. Cellular Physiology and Biochemistry. 41(1): 55-66.
  11. Panwar P, Butler G, Jamroz A, Overall CM, Brömme D. (2017). Aging-associated modifications of collagen affect its degradation by matrix metalloproteinases. Matrix Biology. [Epub ahead of print: June 17].
  12. Kruglyak N, Williams DE, Chen H, Law S, Kaleta J, Villanueva I, Davies JE, Andersen RJ, Brömme D. (2017). Leupeptazin,a highly modified tripeptide isolated from cultures of a Streptomyces inhibits cathepsin K. Bioorganic & Medicinal Chemistry Letters. 27(6): 1397-1400.
  13. Law S, Andrault PM, Aguda A, Nguyen N, Kruglyak N, Brayer G, Bromme D. (2017). Identification of mouse cathepsin K structural elements that regulate the potency of odanacatib. Biochemical Journal. 474(5): 851-864.
  14. Rodrigues RV, Giannini M, Pascon FM, Panwar P, Brömme D, Manso AP, Carvalho RM. (2017). Effect of conditioning solutions containing ferric chloride on dentin bond strength and collagen degradation. Dental Materials. [Epub ahead of print: Aug. 2].
  15. Wang L, Ma R, Guo Y, Sun J, Liu H, Zhu R, Liu C, Li J, Li L, Chen B, Sun L, Tang J, Zhao D, Mo F, Niu J, Jiang G, Fu M, Brömme D, Zhang D, Gao S. (2017). Antioxidant effect of fructus ligustri lucidi aqueous extract in ovariectomized rats is mediated through Nox4-ROS-NF-κB Frontiers in Pharmacology. 8: 266.
  16. Jing Y, Wu Y, Qin L, Zhang Q, Xin H, Brömme D, Xue L. (2017). Study on exosite inhibitor of cathepsin K from Herba Ecliptae fractions. Acta Parmaceutica Sinica. 52(6): 936-942.
  17. Aguda AH, Lavallee V, Cheng P, Bott TM, Meimetis LG, Law S, Nguyen NT, Williams DE, Kaleta J, Villanueva I, Davies J, Andersen RJ, Brayer GD, Brömme D. (2016). Affinity crystallography: a novel approach to identifying high affinity cathepsin K inhibitors from natural extracts. Journal of Natural Products. 79(8): 1962-1970.
  18. Brömme D, Panwar P, Turan S. (2016). Cathepsin K osteoporosis trials, pycnodysostosisand mouse deficiency models: commonalities and differences. Expert Opinion in Drug Discovery. 11(5): 457-470.
  19. Panwar P, Søe K, Guido RV, Bueno RV, Delaisse JM, Brömme D. (2016). A novel approach to inhibit bone resorption: exosite inhibitors against cathepsin K. British Journal of Pharmacology. 173(2): 396-410.
  20. Bailleul G, Kravtzoff A, Joulin-Giet A, Lecaille F, Labas V, Meudal H, Loth K, Teixeira-Gomes AP, Gilbert FB, Coquet L, Jouenne T, Brömme D, Schouler C, Landon C, Lalmanach G, Lalmanach AC. (2016). The unusual resistance of avian defensin AvBD7 to proteolytic enzymes preserves its antibacterial activity. PloS One. 11(8): e0161573.
  21. Andrault PM, Samsonov SA, Weber G, Coquet L, Nazmi K, Bolscher JG, Lalmanach AC, Jouenne T, Brömme D, Pisabarro MT, Lalmanach G, Lecaille F. (2015). Antimicrobial peptide LL-37 is both a substrate of cathepsins S and K and a selective inhibitor of cathepsin L. Biochemistry. 54(17): 2785-2798.
  22. Sharma V, Panwar P, O’Donoghue AJ, Cui H, Guido RV, Craik CS, Brömme D. (2015). Structural requirements for the collagenase and elastase activity of cathepsin K and its selective inhibition by an exosite inhibitor. The Biochemical Journal. 465(1): 163-173.
  23. Wieczorek A, Rezaei N, Chan CK, Xu C, Panwar P, Brömme D, Merschrod S EF, Forde NR. (2015). Development and characterization of a eukaryotic expression system for human type II procollagen. BMC Biotechnology. 15(1): 112.
  24. Panwar P, Lamour G, Mackenzie NC, Yang H, Ko F, Li H, Brömme D. (2015). Changes in structural- mechanical properties and degradability of collagen during aging-associated modifications. The Journal of Biological Chemistry. 290(38): 23291-23306.
  25. Aguda AH, Panwar P, Du X, Nguyen NT, Brayer GD, Brömme D. (2014). Structural basis of collagen fiber degradation by cathepsin K. Proceedings of the National Academy of Sciences of the United States of America. 111(49): 17474-17479.
  26. Guo Y, Li Y, Xue L, Severino RP, Gao S, Niu J, Qin LP, Zhang D, Brömme D. (2014). Salvia miltiorrhiza: an ancient Chinese herbal medicine as a source for anti-osteoporotic drugs. Journal of Ethnopharmacology. 155(3): 1401-1416.
  27. Zheng CJ, Zhang XW, Han T, Jiang YP, Tang JY, Brömme D, Qin LP. (2014). Anti-inflammatory and anti- osteoporotic lignans from Vitex negundo Fitoterapia. 93: 31-38.
  28. Panwar P, Du X, Sharma V, Lamour G, Castro M, Li H, Brömme D. (2013). Effects of cysteine proteases on the structural and mechanical properties of collagen fibers. The Journal of Biological Chemistry. 288(8): 5940-5950.
  29. Nallaseth FS, Lecaille F, Li Z, Brömme D. (2013). The role of basic amino acid surface clusters on the collagenase activity of cathepsin K. Biochemistry. 52(44): 7742-7752.
  30. Du X, Chen NL, Wong A, Craik CS, Brömme D. (2013). Elastin degradation by cathepsin V requires two exosites. Journal of Biological Chemistry. 288(48): 34871-34881.

Education

  • Ph.D. (Biochemistry), Martin Luther University Halle-Wittenberg, GDR, 1983.
  • M.Sc. (Biochemistry), Martin Luther University Halle-Wittenberg, GDR, 1980.
  • D.Sc. (Biochemistry), Friedrich-Schiller-University Jena, Germany, 1997.