Multiple Sclerosis Functional Genomics

Investigators

A/Prof David Booth, University of Sydney, Westmead Millennium Institute

Funding

MSRA Senior Research Fellow
$650,000 over 5 years

Summary

Associate Professor David Booth is a pivotal member of the MS Research Australia-funded research platform - The ANZgene Consortium for MS genetics - and over the last few years has contributed enormously to our understanding of the genetic basis for susceptibility to MS. In recognition of this, and to support his continued contribution to this field of research, he was awarded the inaugural Senior Research Fellowship from MS Research Australia and was appointed as an Associate Professor of the University of Sydney in January 2010.

David gained his PhD from Imperial College London, in 1992. He then studied the genetic basis of Amyloidoisis and Familial Mediterranean Fever at The Royal Free Hospital in London, before returning to Australia in 2001 to investigate which genes cause susceptibility to Multiple Sclerosis and why.

A/Prof Booth’s group were the first to identify that variations in the gene that codes for the Interleukin-7 Receptor (IL7R) are associated with MS, and to identify the possible mechanisms. He has made significant contributions to the International Multiple Sclerosis Genetics Consortium (IMSGC) and the Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene). These large-scale collaborations have together identified the genes conferring the largest effect on susceptibility to MS. His main task is now to determine why these genes contribute to MS disease. A/Prof Booth is also working to identify biomarkers - molecules that can easily be screened for in blood or cerebrospinal fluid- for clinical use in MS diagnosis and prognosis.

A/Prof Booth’s other research interests also include studies into the genetic basis for differing responses to treatment for other immune conditions, notably hepatitis C and HIV.

In 2010, David was an author on 13 publications of novel discoveries in international scientific journals (see below), and has won, with others, an NHMRC project grant on immunogenetics, two Merck Serono research grants and a grant from the Rebecca Cooper Foundation for IL7R studies. A/Prof Booth was also the recipient of an MSRA project grant on MS genes and function, which commenced in 2011. He was invited to speak on MS genetics at the American Association of Neurologists Meeting in Toronto (April 2010), and the Westmead Autoimmune Disease Symposium (August, 2010). He won the Westmead Millennium Institute Science Prize in 2010.

Publications in 2010

Grebely J, Petoumenos K, Hellard M, Matthews GV, Suppiah V, Applegate T, Yeung B, Marks P, Rawlinson W, Lloyd AR, Booth D, Kaldor JM, George J, Dore GJ; ATAHC Study Group. Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection. Hepatology. 2010 Oct;52(4):1216-24.

Rajasuriar R, Booth D, Solomon A, Chua K, Spelman T, Gouillou M, Schlub TE, Davenport M, Crowe S, Elliott J, Hoy J, Fairley C, Stewart G, Cameron P, Lewin SR. Biological determinants of immune reconstitution in HIV-infected patients receiving antiretroviral therapy: the role of interleukin 7 and interleukin 7 receptor α and microbial translocation.J Infect Dis. 2010 Oct 15;202(8):1254-64.

Riveros C, Mellor D, Gandhi KS, McKay FC, Cox MB, Berretta R, Vaezpour SY, Inostroza-Ponta M, Broadley SA, Heard RN, Vucic S, Stewart GJ, Williams DW, Scott RJ, Lechner-Scott J, Booth DR, Moscato P; ANZgene Multiple Sclerosis Genetics Consortium. A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis. PLoS One. 2010 Dec 1;5(12):e14176.

Field J, Browning SR, Johnson LJ, Danoy P, Varney MD, Tait BD, Gandhi KS, Charlesworth JC, Heard RN; Australia and New Zealand Multiple Sclerosis Genetics Consortium, Stewart GJ, Kilpatrick TJ, Foote SJ, Bahlo M, Butzkueven H, Wiley J, Booth DR, Taylor BV, Brown MA, Rubio JP, Stankovich J. A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis. PLoS One. 2010 Oct 26;5(10):e13454.

Ahlenstiel G, Booth DR, George J. IL28B in hepatitis C virus infection: translating pharmacogenomics into clinical practice. J Gastroenterol. 2010 Jul 16. [Epub ahead of print] IF:2.9

International Multiple Sclerosis Genetics Consortium (IMSGC incl. Booth DR). IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci. Genes Immun. 2010 Jul;11(5):397-405. Epub 2010 Jun 17 IF:4.2

Cox MB, Cairns MJ, Gandhi KS, Carroll AP, Moscovis S, Stewart GJ, Broadley S, Scott RJ, Booth DR, Lechner-Scott J; ANZgene Multiple Sclerosis Genetics Consortium. MicroRNAs miR-17 and miR-20a Inhibit T Cell Activation Genes and Are Under-Expressed in MS Whole Blood. PLoS One. 2010 Aug 11;5(8). pii: e12132. IF:4.3
 

International Multiple Sclerosis Genetics Consortium (IMSGC)*, Booth DR, Heard RN, Stewart GJ, Cox M, Scott RJ, Lechner-Scott J, Goris A, Dobosi R, Dubois B, Saarela J, Leppä V, Peltonen L, Pirttila T, Cournu-Rebeix I, Fontaine B, Bergamaschi L, D'Alfonso S, Leone M, Lorentzen AR, Harbo HF, Celius EG, Spurkland A, Link J, Kockum I, Olsson T, Hillert J, Ban M, Baker A, Kemppinen A, Sawcer S, Compston A, Robertson NP, De Jager PL, Hafler DA, Barcellos LF, Ivinson AJ, McCauley JL, Pericak-Vance MA, Oksenberg JR, Hauser SL, Sexton D, Haines J. Lack of support for association between the KIF1B rs10492972[C] variant and multiple sclerosis. Nat Genet. 2010 Jun;42(6):469-70.IF:34.3

Gandhi KS, McKay FC, Diefenbach E, Crossett B, Schibeci SD, Heard RN, Stewart GJ, Booth DR, Arthur JW. Novel approaches to detect serum biomarkers for clinical response to interferon-beta treatment in multiple sclerosis. PLoS One. 2010 May 5;5(5):e10484. IF:4.3
 

Jensen CJ, Stankovich J, Van der Walt A, Bahlo M, Taylor BV, van der Mei IA, Foote SJ, Kilpatrick TJ, Johnson LJ, Wilkins E, Field J, Danoy P, Brown MA; Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene, incl Booth DR), Rubio JP, Butzkueven H. Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients. PLoS One. 2010 Apr 2;5(4):e10003. IF:4.3

Gandhi KS, McKay FC, Cox M, Riveros C, Armstrong N, Heard RN, Vucic S, Williams DW, Stankovich J, Brown M, Danoy P, Stewart GJ, Broadley S, Moscato P, Lechner-Scott J, Scott RJ, Booth DR, ANZgene Multiple Sclerosis Genetics Consortium The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis Human Molecular Genetics 2010 Feb 27. [Epub ahead of print]IF:7.4

Hoe E., McKay FC , Schibeci SD, Gandhi K, Heard RN, Stewart GJ, Booth DR Functionally significant differences in expression of disease-associated IL-7Rhaplotypes in CD4 T cells and dendritic cells J Immunol 2010 Mar 1;184(5):2512-7. Epub 2010 Jan 22.IF:6.4

Hoe E, McKay FC, Schibeci S, Heard R, Stewart GJ, Booth DR Interleukin 7 receptor alpha chain (IL7R) haplotypes vary in their influence on multiple sclerosis susceptibility and response to interferon beta J Interferon Cytokine Res. 2010 Feb 28. [Epub ahead of print] IF:2.7
 

Updated: 09/06/2011