Awarded the degree of Doctor of Philosophy in Immunology by Flinders University in 1982 (PhD thesis: Human B-cell differentiation)
I am a NH&MRC Senior Research Fellow/ Chief Medical Scientist in the Department of Chemical Pathology at the Women’s and Children’s Hospital. I am affiliated with the University of Adelaide, through the Department of Paediatrics at the Women’s and Children’s Hospital. My research is focused on the biochemistry of genetic disease using molecular, immunochemistry, and cell biology techniques.
I am currently head of the Immunochemistry-Cell Biology section of the Lysosomal Diseases Research Unit in the Department of Chemical Pathology Women’s and Children’s Hospital and am a chief investigator on a NH&MRC program grant entitled ‘Lysosomal Storage Disorders: Diagnosis, Treatment and Biology’. My current research interests include the cell biology of lysosomes for normal controls and lysosomal storage disorder patients, pathogenic processes in lysosomal storage disorder patients and immune response to enzyme replacement therapy during the treatment of patients with lysosomal storage disorders.
The cell biology of normal control and lysosomal storage disorder patient lysosomes
The global aim of this project is to study the biology of the vacuolar network (ie. endoplasmic reticulum, endosomes and lysosomes) including protein folding and processing of lysosomal enzymes, lysosomal biogenesis, lysosomal function and alterations in these mechanisms which occur during disease states. It has been postulated that the biogenesis of lysosomes is important for the comprehension of normal cellular function, but it is crucial to the understanding of lysosomal storage disorders and the development of pathophysiology in patients. The lysosomal storage disorders Mucopolysaccharidosis type I (MPS I), type II (MPS II), type IVa (MPS IVa) and type VI (MPS VI) are genetic diseases, which are being studied as model systems.
Immune response to enzyme replacement therapy
The Lysosomal Diseases Research Unit’s primary aim is to provide a safe and effective therapy for the severe genetic diseases known as lysosomal storage disorders (LSD). We have been extremely active in the development of enzyme replacement therapy (ERT) for mucopolysaccharidosis (MPS) patients, which is a subgroup of LSD. In preliminary observations, lysosomal storage disorder patients and animal models treated with ERT, have demonstrated specific antibody responses to the replacement protein(s). We now recognise that the generation of high titre antibodies to a replacement protein can have a significant impact on the efficacy of a treatment regimen.
Brooks DA, Hopwood JJ. and King BM. (1998): Immune response to enzyme replacement therapy : Clinical signs of hypersensitivity reactions and altered enzyme distribution in a high titre rat model. Biochemica et Biophysica Acta, 1407: 163-172.Bunge S, Clements PR, Byers S, Kliejer WJ, Brooks DA. and Hopwood JJ. (1998): Genotype-phenotype correlations in mucopolysaccharidosis type I using enzyme kinetics, immunoquantification and in vitro turnover studies. Biochemica et Biophysica Acta, 1407: 249-256.
Meikle PJ, Yan M, Ravenscroft EM, Isaac L, Hopwood JJ. and Brooks DA. (1999): Altered trafficking and turnover of LAMP-1 in Pompe disease-affected cells. Molecular Genetics and Metabolism, 66: 179-188.
Meikle PJ, Ranieri E, Ravenscroft EM, Hua CT, Brooks DA. and Hopwood JJ. (1999): Newborn screening for lysosomal storage disorders. Journal of Tropical Medicine and Public Health, 30: 104-110.
Bradford TM, Gething M-J, Davey R, Hopwood JJ. and Brooks DA. (1999): Processing of normal lysosomal and mutant N-acetylgalactosamine 4-sulfatase : BiP (immunoglobulin heavy-chain binding protein) may interact with critical protein contact sites. Biochemical Journal, 341: 193-201.
Simonaro CM, Haskins ME, Abkowitz JL, Hopwood JJ, Brooks DA, Zhang J. and Schuchman, E. (1999): Autologous transplantation of retrovirally-transduced bone marrow or neonatal blood cells into cats can lead to long-term engraftment in the absence if myeloablation. Gene Therapy, 6: 107-113.
Turner CT, Hopwood JJ, Bond CS. and Brooks DA. (1999): Immune response to enzyme replacement therapy: 4-Sulphatase epitope reactivity of plasma antibodies from MPS VI cats. Molecular Genetics and Metabolism, 67: 194-205.
Brooks DA. (1999): Introduction: Molecular chaperones of the ER; Their role in protein folding and genetic disease. Seminars in Cell and Developmental Biology, 10: 441-442.
Brooks DA. (1999): Minireview: "Immune response to enzyme replacement therapy in lysosomal storage disorder patients and animal models". Molecular Genetics and Metabolism, 68: 268-275.
Isaac L, Karageorgos L, Brooks DA, Hopwood JJ, and Meikle PJ. (2000): Regulation of the lysosome associated membrane protein (LAMP-1) in a sucrose model of lysosomal storage. Experimental Cell Research, 254: 204-209.
Turner CT, Hopwood JJ, and Brooks DA. (2000): Enzyme replacement therapy in mucopolysaccharidosis type I: Altered distribution and targeting of a-L-iduronidase in immunised rats. Molecular Genetics and Metabolism, 69: 277-285.
Mullock BM, Smith CW, Bright NA, Ihrke G, Lindsay M, Parkinson EJ, Brooks DA, Parton RG, James DE, Luzio PJ, and Piper RC. (2000): Syntaxin-7 is localised to late endosome compartments, associates with vamp 8, and is required for endosome/lysosome fusion. Molecular Biology of the Cell, 11: 3137-3153.
Brooks DA. (2000) Chapter 4: Application of monoclonal antibodies to the study of molecules in solution. Introduction to Biotechniques series, BIOS Scientific Publishers, Oxford, (ed. H. Zola), pp 81-100.
Keeling KM, Brooks DA, Hopwood JJ, Li P, Thompson JN, and Bedwell DM. (2001): Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of a-L-Iduronidase activity and reduces lysosomal glycosaminoglycan accumulation. Human Molecular Genetics, 10: 291-299.
Brooks DA, Fabrega S, Hein LK, Parkinson EJ, Durand P, Yogalingam G, Matte U, Giugliani R, Dasvarma A, Eslahpazire J, Henrissat B, Mornon J-P and Lehn P. (2001): Glycosidase active site mutations in human _-L-iduronidase. Glycobiology, 11, 741-750.
Bradford TM, Litjens T, Parkinson EJ, Hopwood JJ, and Brooks DA. (2002): Muccopolysaccharidosis type VI : A Y210C mutation causes either altered handling or function of N-acetylgalactosamine 4-sulfatase at multiple points in the vacuolar network. Biochemistry, In press.
Brooks DA. (2003): Protein co- and post-translational modification. Encyclopedia of the Human Genome, Nature Publishing Group, Submitted by invitation.
