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Mark Y. Sangster, Ph.D.

Contact Information

Faculty Appointments

Biography

Research

Overview

Virus-specific antibodies play a key role in providing a protective barrier to infection and in facilitating viral clearance once an infection is established. Antibody-producing cells or plasma cells are generated from B cells that divide and differentiate following recognition of specific antigen. A critical requirement for optimal antibody responses is the cognate help delivered to activated B cells by CD4 T cells. This help is important for directing antibody isotype switching in B cells, the process by which B cells switch from expressing IgM to expressing alternative isotypes (such as IgG1, IgG2a, and IgA in the mouse) with different functional characteristics. In addition, cognate T cell help is critical if activated B cells are to participate in germinal center reactions, where affinity maturation of the antibody response takes place and the cellular elements of B cell memory are generated. These elements include long-lived plasma cells, which maintain high levels of protective antibodies, and a population of memory B cells that will respond with rapid antibody production on re-exposure to cognate antigen. This brief overview grossly simplifies a remarkable and complex process that is regulated at many levels in ways that modulate the kinetics, magnitude, and quality of the acute B cell response, as well as characteristics of dispersed plasma cell and memory B cell populations. In general terms, our research is aimed at understanding the characteristics of optimally effective B cell responses and applying this knowledge towards the improvement of vaccination regimens.

Specific Research Interests

Our specific research focus is the B cell response to viruses that infect the respiratory tract (with an emphasis on influenza virus) and to vaccination regimens designed to generate B cell-mediated protection against these viruses. Particular research interests include: (i) regulation of the acute B cell response to infection and vaccination and the differentiation pathways that generate B cell memory and virus-neutralizing antibodies, (ii) aspects of B cell memory (plasma cells, memory B cells) in the respiratory tract, including mechanisms of localization, role in protection, and relationship to form of immunization, and (iii) regulation of IgA production and the establishment of antibody-mediated protection at mucosal surfaces.

Credentials

Education

1984
BS | Australia-U Western Australia - Perth
Genetics

1991
PhD | Australia-U Western Australia - Perth
Genetics

Awards

1991
Athelstan and Amy Saw Medical Research Award
Sponsor: University of Western Australia

1985
Australian Commonwealth Postgraduate Award for Dissertation Research

1984
Swan Brewery Prize for Undergraduate Honors Thesis
Location: University of Western Australia

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Publications

Journal Articles

9/28/2019
Sangster MY, Nguyen PQT, Topham DJ. "Role of Memory B Cells in Hemagglutinin-Specific Antibody Production Following Human Influenza A Virus Infection." Pathogens.. 2019 Sep 28; 8(4)Epub 2019 Sep 28.

2/6/2019
Tesini BL, Kanagaiah P, Wang J, Hahn M, Halliley JL, Chaves FA, Nguyen PQT, Nogales A, DeDiego ML, Anderson CS, Ellebedy AH, Strohmeier S, Krammer F, Yang H, Bandyopadhyay S, Ahmed R, Treanor JJ, Martinez-Sobrido L, Golding H, Khurana S, Zand MS, Topham DJ, Sangster MY. "Broad hemagglutinin-specific memory B cell expansion by seasonal influenza virus infection reflects early-life imprinting and adaptation to the infecting virus." Journal of virology.. 2019 Feb 6; Epub 2019 Feb 06.

8/2018
Topham DJ, Nguyen P, Sangster MY. "Pandemic influenza vaccines: what they have taught us about B cell immunology." Current opinion in immunology.. 2018 Aug 0; 53:203-208. Epub 2018 Jun 26.

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