- ADJUNCT PROFESSOR Genetics and Genomic Sciences
D.Sc., Martin - Luther University
Ph.D., Martin - Luther University
Protein expression and purification, enzymology, histology, animal models, protease involvement in arthritis and atherosclerosis
Proteases and Diseases
\r\nMany human diseases are characterized by an excessive proteolytic degradation of proteins of the extracellular matrix (e.g., arthritides, osteoporosis, 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, histology, animal models and a wide range of collaborations with clinical and biotech institutions. \r\n
Hou WS, Li Z, Gordon RE, Chan K, Klein MJ, Levy R, Keysser M, Keyszer G, Bromme D, Cathepsin K. A critical protease in synovial fibroblast-mediated collagen degradation. Am J Pathol 2001; 159: 2167-2177.
Wieczerzak E, Drabik P, Lankiewicz L, Oldziej S, Grzonka Z, Abrahamson M, Grubb A, Bromme D. Azapeptides Structurally Based upon Inhibitory Sites of Cystatins as Potent and Selective Inhibitors of Cysteine Proteases J. Med Chem 2002; 45: 4202-4211.
Hou WS, Li W, Keyszer G, Weber E, Levy R, Klein MJ, Gravallese EM, Goldring SR, Bromme D. Comparison of cathepsins K and S expression within the rheumatoid and osteoarthritic synovium. Arthritis&Rheumatism 2002; 46: 663-674.
Lecaille F, Kaleta J, Bromme D. Human and Parasitic Papain-like Cysteine Proteases: Their Role in Physiology and Pathology. Chem Rev 2002; 102: 4459-4488.
Li Z, Hou WS, Escalante C, Gelb BD, Bromme D. Collagenase activity of cathepsin K requires chondroitin sulfate. J Biol Chem 2002; 277: 28669-28676.
Lecaille F, Choe Y, Brandt W, Li Z, Charles S, Craik CS, Bromme D. Selective Inhibition of the Collagenolytic Activity of Human Cathepsin K by Altering its S2 Subsite Specificity. Biochemistry 2002; 41: 8447-8454.
Alves MF, Puzer L, Cotrin SS, Juliano MA, Juliano L, Bromme D, Carmona AK. S3 to S3' subsite specificity of recombinant human cathepsin K and development of selective internally quenched fluorescent substrates. Biochem J 2003; 373: 981-986.
Tolosa E, Li W, Yasuda Y, Denzin LK, Stevanovic S, Driessen C, Kurek R, Weber E, Melms A, Bromme D, Cathepsin V. Cathepsin V is involved in the Degradation of Invariant Chain in Human Thymus and is Overexpressed in Myasthenia Gravis. Clin Invest 2003; 112: 517-526.
Hou WS, Li Z, Buttner FH, Bartnik E, Bromme D. Cleavage Site Specificity of Cathepsin K towards Cartilage Proteoglycans: Efficient Degradation of Link Protein and Aggrecan Biol. Chem 2003; 384: 891-897.
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