Professor, Oral Biological and Medical Sciences, DentistryAssociate Member, Biochemistry and Molecular Biology, MedicineCanada Research Chair in Proteases and Diseases
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.
Current research topics:
Antigen Presentation and Autoimmune Disease
Cathepsin K and Collagen Degradation
Bone and Joint Diseases
D.Sc. (Biochemistry), Friedrich-Schiller-University Jena, Germany, 1997
Ph.D. (Biochemistry), Martin Luther University Halle-Wittenberg, GDR, 1983
M.Sc. (Biochemistry), Martin Luther University Halle-Wittenberg, GDR, 1980
- Du X, Chen NL, Wong A, Craik CS, Brömme D. Elastin degradation by cathepsin V requires two exosites. J Biol Chem. 2013 Nov 29;288(48):34871-81.
- Panwar P, Du X, Sharma V, Lamour G, Castro M, Li H, Brömme D. Effects of cysteine proteases on the structural and mechanical properties of collagen fibers. J Biol Chem. 2013 Feb 22;288(8):5940-50.
- Sage J, Leblanc-Noblesse E, Nizard C, Sasaki T, Schnebert S, Perrier E, Kurfurst R, Brömme D, Lalmanach G, Lecaille F. Cleavage of nidogen-1 by cathepsin S impairs its binding to basement membrane partners. PLoS One. 2012;7(8):e43494.
- Oliveira M, Assis DM, Paschoalin T, Miranda A, Ribeiro EB, Juliano MA, Brömme D, Christoffolete MA, Barros NM, Carmona AK. Cysteine cathepsin S processes leptin, inactivating its biological activity. J Endocrinol. 2012 Aug;214(2):217-24.
- Marques EF, Bueno MA, Duarte PD, Silva LR, Martinelli AM, dos Santos CY, Severino RP, Brömme D, Vieira PC, Corrêa AG. Evaluation of synthetic acridones and 4-quinolinones as potent inhibitors of cathepsins L and V. Eur J Med Chem. 2012 Aug;54:10-21.
- Zhang D, Huang C, Yang C, Liu RJ, Wang J, Niu J, Brömme D. Antifibrotic effects of curcumin are associated with overexpression of cathepsins K and L in bleomycin treated mice and human fibroblasts. Respir Res. 2011 Nov 29;12:154.
- Kirschner R, Hubmacher D, Iyengar G, Kaur J, Fagotto-Kaufmann C, Brömme D, Bartels R, Reinhardt DP. Classical and neonatal Marfan syndrome mutations in fibrillin-1 cause differential protease susceptibilities and protein function. J Biol Chem. 2011 Sep 16;286(37):32810-23.
- Zhang D, Leung N, Weber E, Saftig P, Brömme D. The effect of cathepsin K deficiency on airway development and TGF-β1 degradation. Respir Res. 2011 May 31;12:72.
- Piovan L, Alves MF, Juliano L, Brömme D, Cunha RL, Andrade LH. Structure-activity relationships of hypervalent organochalcogenanes as inhibitors of cysteine cathepsins V and S. Bioorg Med Chem. 2011 Mar 15;19(6):2009-14.
- Severino RP, Guido RV, Marques EF, Brömme D, da Silva MF, Fernandes JB, Andricopulo AD, Vieira PC. Acridone alkaloids as potent inhibitors of cathepsin V. Bioorg Med Chem. 2011 Feb 15;19(4):1477-81. Epub 2011 Jan 1.
- Samokhin AO, Gauthier JY, Percival MD, Brömme D. Lack of cathepsin activities alter or prevent the development of lung granulomas in a mouse model of sarcoidosis. Respir Res. 2011 Jan 20;12:13.
- Cherny MM, Lecaille F, Kienitz Deceased M, Nallaseth FS, Li Z, James MN, Bromme D. Structure-activity analysis of cathepsin K/chondroitin 4-sulfate interactions. J Biol Chem. 2010 Dec 30.
- Samokhin AO, Lythgo PA, Gauthier JY, Percival MD, Brömme D. Pharmacological inhibition of cathepsin S decreases atherosclerotic lesions in Apoe-/- mice. J Cardiovasc Pharmacol. 2010 Jul;56(1):98-105.
- Coppini LP, Barros NM, Oliveira M, Hirata IY, Alves MF, Paschoalin T, Assis DM, Juliano MA, Puzer L, Brömme D, Carmona AK. Plasminogen hydrolysis by cathepsin S and identification of derived peptides as selective substrate for cathepsin V and cathepsin L inhibitor. Biol Chem. 2010 May;391(5):561-70.
- Samokhin AO, Wilson S, Nho B, Lizame ML, Musenden OE, Brömme D. Cholate-containing high-fat diet induces the formation of multinucleated giant cells in atherosclerotic plaques of apolipoprotein E-/- mice. Arterioscler Thromb Vasc Biol. 2010 Jun;30(6):1166-73. Epub 2010 Mar 4.
- Samokhin AO, Bühling F, Theissig F, Brömme D.ApoE-deficient mice on cholate-containing high-fat diet reveal a pathology similar to lung sarcoidosis. Am J Pathol. 2010 Mar;176(3):1148-56. Epub 2010 Jan 21.