Professor Graham V. Brown

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Department of Medicine (RMH/WH)
4th Floor, Clinical Sciences Building
Royal Melbourne Hospital
Royal Parade
Parkville, Vic. 3050 AUSTRALIA

Tel: +61 3 8344 5490 Fax: +61 3 9347 1863
Email: gvb@unimelb.edu.au
See: Full Research Profile

Professor Brown, MB BS Melb. MPH Harv. PhD Melb. FRACP FAFPHM FACTM, and his laboratory-based research now focus on Plasmodium falciparum, the parasite responsible for severe malaria in children and pregnant women. From its protected environment inside human red blood cells, the malaria parasite exports proteins to the surface of the infected cells.

Professor Brown and his malaria research laboratory colleagues are studying the mechanism by which parasites vary these proteins (antigen variation) and how different variants cause disease by adhering in different body organs to receptors such as Chondroitin sulfate A and hyaluronic acid—descibed by his graduate students Stephen Rogerson and James Beeson. This family of parasite proteins could be a target of protective immunity.

Under Professor Brown's leadership, the Department also hosts the Centre for Clinical Research Excellence in Infectious Diseases, which has special interests in clinical virology, illness in returned travellers, refugees and immigrant health, and the use of computers to assist in decision making for selection of antibiotics.

Most Relevant Recent Publications

1. Beeson JG, Mann EJ, Byrne TJ, Caragounis A, Elliott SR, Brown GV & Rogerson SJ (2006). Antigenic differences and conservation among placental type Plasmodium falciparum-infected erythrocytes and acquisition of variant-specific and cross-reactive antibodies. J Infect Dis., 1 March, 193(5):721–30.
2. Elliott SR, Brennan AK, Beeson JG, Tadesse E, Molyneux ME, Brown GV & Rogerson SJ (2005). Placental malaria induces variant specific antibodies of the cytophilic subtypes, G1 (IgG1) and IgG3, that correlate with adhesion inhibitory activity. Infect Immun, September, 73(9):5903–07.
3. Elliott SR, Duffy MF, Byrne TJ, Beeson JG, Mann EJ, Wilson DW, Rogerson SJ & Brown GV (2005). Cross-reactive surface epitopes on chondroitin sulfate A-adherent Plasmodium falciparum-infected erythrocytes are associated with transcription of var2csa. Infect Immun, 73(5):2848–56.
4. Duffy MF, Byrne TJ, Elliott SR, Wilson DW, Rogerson SJ, Beeson JG, Noviyanti R & Brown GV (2005). Broad analysis reveals a consistent pattern of var gene transcription in Plasmodium falciparum repeatedly selected for a defined adhesion phenotype. Mol Microbiol, 56(3):774–88.

5. Beeson JG, Rogerson SJ, Cooke BM, Reeder JC, Chai W, Lawson AM, Molyneux ME & Brown GV (2000). Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria. Nature Med. 6:86–90. [c91] [if 30.5]
   This paper demonstrated that parasites can bind to an alternate receptor in the placenta, an important finding for programs attempting to develop vaccines for prevention of placental malaria.

6. Duffy MF, Brown GV, Basuki W, Krejany EO, Noviyanti R, Cowman AF & Reeder JC (2002). Transcription of multiple var genes by individual, trophozoite stage Plasmodium falciparum cells expressing a chrondroitin sulfate A binding phenotype. Mol. Microbiol. 43:1285–93. [c13] [if5.5]
   For the first time it was shown that individual trophozoite infected cells can express multiple var genes

7. Genton B, Betuela I, Felger I, Al-Yaman F, Anders RF, Saul A, Rare L, Baisor M, Lorry K, Brown GV, Pye D, Irving DO, Smith TA, Beck H-P & Alpers MP (2002). A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a Phase 1-2b trial in Papua New Guinea. J. Infect. Dis. 185: 820–7. [c34] [if4.4]
   This study demonstrated an important landmark of a public-private partnership in showing efficacy of a combination vaccine against P.falciparum malaria in Papua New Guinea. I had a long involvement in the planning many clinical trials in this vaccine development programme.

8. Leder K, Sundararajan V, Weld L, Pandey P, Brown G, Torresi J & GeoSentinel Surveillance Group. (2003) Respiratory tract infections in travellers: a review of the GeoSentinel surveillance network. Clin. Infect. Dis. 36: 399–406. [c3] [if5.3]
   This article contains novel data providing important information regarding respiratory infections of travellers, of relevance to prevention by influenza vaccine and surveillance at times of epidemic SARS.

9. Beeson JG, Mann EJ, Elliott SR, Lema VM, Tadesse E, Molyneux ME, Brown GV & Rogerson SJ (2004). Antibodies to variant surface antigens of Plasmodium falciparum -infected erythrocytes and adhesion inhibitory antibodies are associated with placental malaria and have overlapping and distinct targets. J. Infect. Dis. 189: 540–51. [c5] [if4.4]
   This data is relevant to development of immunity to malaria in pregnancy. It showed that antibodies that inhibit parasite invasion and antibodies that bind to variant antigens have distinct and overlapping epitopes and may be acquired independently with different roles in immunity.

10. Beeson JG & Brown GV (2004) Plasmodium falciparum-infected erythrocytes demonstrate dual specificity for adhesion to hyaluronic acid and chondroitin sulfate A and have distinct adhesive properties. J. Infect. Dis. 189:169–79. [c3] [if4.4]
    The editorial commentary accompanying this major article (Smith & Miller, J Infect Dis 2004, 189:165–8) included the comments: 'These new findings begin to resolve previous contradictions and suggest important controls for future studies that will allow re-evaluation of the role of HA in placental sequestration'. The results described were very important for the field, and relevant for programs designed to develop vaccines against placental malaria.

11. Duffy MF, Byrne TJ, Elliott SR, Wilson DW, Rogerson SJ, Beeson JG, Noviyanti R & Brown G (2005). Broad analysis reveals a consistent pattern of var gene transcription in Plasmodium falciparum repeatedly selected for a defined adhesion phenotype. Mol Micro (in press).
    This paper demonstrated that different parasite isolates selected for adhesion to a particular receptor demonstrate increased transcription of a particular gene or it homologue

Current Grants

2008-2010    Transcriptional control of antigenic variation in the malaria parasite Plasmodium falciparum. ARC Discovery Project DP0879293. MF Duffy, GV Brown

2006-2010    Host parasite interactions: Disease, pathogenesis and control. NHMRC Program Grant 406601 Brown (CIB) $13,500,000 (in association with AF Cowman, BS Crabb, E Handman, MJ McConville, GI McFadden, L Schofield, TP Speed)

The molecular basis of host-pathogen interactions
National Health and Medical Research Council Program Grant
2002–06: $11,500,000