White, Ann - University of Southampton

个人简介

Ann White obtained her PhD from the MRC Clinical Research Centre, Harrow in 1991. She then spent 10 years in the United States working on lipoprotein metabolism first as a post-doc at the Southwest Foundation for Biomedical Research, San Antonio, Texas, then as a tenure-track Assistant Professor in Internal Medicine at the University of Texas Southwestern Medical Center in Dallas. After returning to the UK in 2001 and a career break with her young children, Ann joined Professor Martin Glennie at the University of Southampton in 2005, where she is now an established researcher in the Antibody and Vaccine Group of the Cancer Sciences Unit Ann’s research in Southampton is focused in the area of cancer immunotherapy. Her studies are aimed at understanding the molecular mechanisms that drive the therapeutic effects of anti-cancer monoclonal antibodies. In particular, she is interested in exploring the roles that antibody isotype and Fc receptor interactions play in determining the efficacy of agonistic antibodies. Her work has been pivotal in delineating the molecular pathways that contribute to the contrasting mechanisms of action of different antibody drugs with direct implication for drug development. As a member of the ‘Antibody Discovery’ team, Ann’s work is primarily funded by Cancer Research UK (CRUK) as well as a collaborative EU initiative with the goal of translating laboratory based research discovery into improved therapeutics for clinical trials. Ann also has industrial links and is principal investigator on a research contract with a large pharmaceutical company. As well as basic research, Ann is involved in the supervision and examination of undergraduate students, medical students and PhD students in the laboratory.

研究领域

Dr White’s research is focused on the optimisation of immunostimulatory monoclonal antibody (mAb) based anti-cancer drugs designed to induce anti-cancer immunity. One target in development is the TNF receptor superfamily member, CD40, an essential co-stimulatory receptor found on a number of key immune cells. CD40 mAb can exert agonistic (stimulatory) or antagonistic (inhibitory) effects on CD40 signaling to stimulate or dampen immune responses, respectively. However, the mechanisms mediating these contrasting effects are unclear. Like other TNF receptors, CD40 is believed to require clustering in the membrane to recruit intracellular signaling molecules and promote immune stimulation. Ann’s research showed that CD40 mAb usually require cross-linking in vivo by the inhibitory Fc receptor, FcγRIIB, to be active. More recently she also demonstrated that FcγR independent activity can be conferred by the human IgG2 isotype due to a unique configuration of disulphide bonds in its hinge region. In addition, ‘superagonistic’ mAb have also been identified that are active independent of isotype and FcγR interaction, which presumably reflects fine epitope binding specificity.

近期论文

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Influence of immunoglobulin isotype on therapeutic antibody function - Beers, S., Glennie, M. and White, A. Published:2016Publication:BloodVolume:127, (9)Page Range:1-6doi:10.1182/blood-2015-09-625343PMID:26764357 Conformation of the human immunoglobulin G2 hinge imparts superagonistic properties to immunostimulatory anticancer antibodies - White, Ann L., Chan, H.T. Claude, French, Ruth R., Willoughby, Jane E., Mockridge, C. Ian, Roghanian, Ali, Penfold, Christine A., Booth, Steven G., Dodhy, Ali, Polak, Marta E., Potter, Elizabeth A., Ardern-Jones, Michael R., Verbeek, J. Sjef, Johnson, Peter W.M., Al-Shamkhani, Aymen, Cragg, Mark S., Beers, Stephen A. and Glennie, Martin J. Published:2015Publication:Cancer CellVolume:27, (1)Page Range:138-148doi:10.1016/j.ccell.2014.11.001PMID:25500122 Fcy receptor dependency of agonistic CD40 antibody in lymphoma therapy can be overcome through antibody multimerization - White, Ann, Dou, Lang, Chan, Hak, Field, Vikki, Mockridge, Christopher, Booth, Steven, Williams, Emily, French, Ruth, Al-Shamkhani, Aymen, Cragg, Mark, Johnson, Peter, Glennie, Martin and Beers, Stephen Published:2014Publication:The Journal of ImmunologyVolume:194, (4)doi:10.4049/jimmunol.1303204PMID:25024386 Fc? receptor dependency of agonistic CD40 antibody in lymphoma therapy can be overcome through antibody multimerization - White, A., Dou, L., Chan, H.T. Claude and Field, V. Published:2014Publication:The Journal of Immunologydoi:10.4049/jimmunol.1303204PMID:25024386 Fc?R??B controls the potency of agonistic anti-TNFR mAbs - White, Ann L., Chan, H. T. Claude, French, Ruth R., Beers, Stephen A., Cragg, Mark S., Johnson, Peter W. M. and Glennie, Martin J. Published:2013Publication:Cancer Immunology and Immunotherapydoi:10.1007/s00262-013-1398-6PMID:23543215