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Mark Sangster

TitleResearch Associate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentMicrobiology and Immunology in the Center for Vaccine Biology and Immunology
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 609
Rochester NY 14642
 
 Awards And Honors
1984     Swan Brewery Prize for Undergraduate Honors Thesis
1985     Australian Commonwealth Postgraduate Award for Dissertation Research
1991     Athelstan and Amy Saw Medical Research Award  | University of Western Australia
 
 Overview
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.

 
 Selected Publications
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  1. Alam S, Knowlden ZA, Sangster MY, Sant AJ. CD4 T Cell Help Is Limiting and Selective during the Primary B Cell Response to Influenza Virus Infection. J Virol. 2014 Jan; 88(1):314-24.
    View in: PubMed
  2. Sangster MY, Baer J, Santiago FW, Fitzgerald T, Ilyushina NA, Sundararajan A, Henn AD, Krammer F, Yang H, Luke CJ, Zand MS, Wright PF, Treanor JJ, Topham DJ, Subbarao K. B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination. Clin Vaccine Immunol. 2013 Jun; 20(6):867-76.
    View in: PubMed
  3. He XS, Sasaki S, Baer J, Khurana S, Golding H, Treanor JJ, Topham DJ, Sangster MY, Jin H, Dekker CL, Subbarao K, Greenberg HB. Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine. J Infect Dis. 2013 Jan; 207(2):288-96.
    View in: PubMed
  4. Sundararajan A, Huan L, Richards KA, Marcelin G, Alam S, Joo H, Yang H, Webby RJ, Topham DJ, Sant AJ, Sangster MY. Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization. PLoS One. 2012; 7(3):e34377.
    View in: PubMed
  5. Sharma S, Sundararajan A, Suryawanshi A, Kumar N, Veiga-Parga T, Kuchroo VK, Thomas PG, Sangster MY, Rouse BT. T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses. Proc Natl Acad Sci U S A. 2011 Nov 22; 108(47):19001-6.
    View in: PubMed
  6. Su X, Sangster MY, D'Souza DH. Time-dependent effects of pomegranate juice and pomegranate polyphenols on foodborne viral reduction. Foodborne Pathog Dis. 2011 Nov; 8(11):1177-83.
    View in: PubMed
  7. Su X, Sangster MY, D'Souza DH. In vitro effects of pomegranate juice and pomegranate polyphenols on foodborne viral surrogates. Foodborne Pathog Dis. 2010 Dec; 7(12):1473-9.
    View in: PubMed
  8. Sundararajan A, Ganapathy R, Huan L, Dunlap JR, Webby RJ, Kotwal GJ, Sangster MY. Influenza virus variation in susceptibility to inactivation by pomegranate polyphenols is determined by envelope glycoproteins. Antiviral Res. 2010 Oct; 88(1):1-9.
    View in: PubMed
  9. Joo HM, He Y, Sundararajan A, Huan L, Sangster MY. Quantitative analysis of influenza virus-specific B cell memory generated by different routes of inactivated virus vaccination. Vaccine. 2010 Mar 2; 28(10):2186-94.
    View in: PubMed
  10. Li Z, Wang H, Xue L, Shin DM, Roopenian D, Xu W, Qi CF, Sangster MY, Orihuela CJ, Tuomanen E, Rehg JE, Cui X, Zhang Q, Morse HC, Morris SW. Emu-BCL10 mice exhibit constitutive activation of both canonical and noncanonical NF-kappaB pathways generating marginal zone (MZ) B-cell expansion as a precursor to splenic MZ lymphoma. Blood. 2009 Nov 5; 114(19):4158-68.
    View in: PubMed
  11. Zeng J, Joo HM, Rajini B, Wrammert JP, Sangster MY, Onami TM. The generation of influenza-specific humoral responses is impaired in ST6Gal I-deficient mice. J Immunol. 2009 Apr 15; 182(8):4721-7.
    View in: PubMed
  12. Joo HM, He Y, Sangster MY. Broad dispersion and lung localization of virus-specific memory B cells induced by influenza pneumonia. Proc Natl Acad Sci U S A. 2008 Mar 4; 105(9):3485-90.
    View in: PubMed
  13. Vanitha DJ, Joo HM, Rouse BT, Sangster MY. Quantitative analysis of herpes simplex virus type 1-specific memory B cells generated by different routes of infection. Virology. 2007 Mar 30; 360(1):136-42.
    View in: PubMed
  14. Li X, Vanitha DJ, Joo HM, He Y, Rouse BT, Sangster MY. A strategy for selective, CD4+ T cell-independent activation of virus-specific memory B cells for limiting dilution analysis. J Immunol Methods. 2006 Jun 30; 313(1-2):110-8.
    View in: PubMed
  15. Lipatov AS, Andreansky S, Webby RJ, Hulse DJ, Rehg JE, Krauss S, Perez DR, Doherty PC, Webster RG, Sangster MY. Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice: the role of cytokines and B- and T-cell responses. J Gen Virol. 2005 Apr; 86(Pt 4):1121-30.
    View in: PubMed
  16. Sangster MY, Riberdy JM, Gonzalez M, Topham DJ, Baumgarth N, Doherty PC. An early CD4+ T cell-dependent immunoglobulin A response to influenza infection in the absence of key cognate T-B interactions. J Exp Med. 2003 Oct 6; 198(7):1011-21.
    View in: PubMed
  17. Marshall DR, Turner SJ, Belz GT, Wingo S, Andreansky S, Sangster MY, Riberdy JM, Liu T, Tan M, Doherty PC. Measuring the diaspora for virus-specific CD8+ T cells. Proc Natl Acad Sci U S A. 2001 May 22; 98(11):6313-8.
    View in: PubMed
  18. Doherty PC, Christensen JP, Belz GT, Stevenson PG, Sangster MY. Dissecting the host response to a gamma-herpesvirus. Philos Trans R Soc Lond B Biol Sci. 2001 Apr 29; 356(1408):581-93.
    View in: PubMed
  19. Wang D, Feng J, Wen R, Marine JC, Sangster MY, Parganas E, Hoffmeyer A, Jackson CW, Cleveland JL, Murray PJ, Ihle JN. Phospholipase Cgamma2 is essential in the functions of B cell and several Fc receptors. Immunity. 2000 Jul; 13(1):25-35.
    View in: PubMed
  20. Sangster MY, Topham DJ, D'Costa S, Cardin RD, Marion TN, Myers LK, Doherty PC. Analysis of the virus-specific and nonspecific B cell response to a persistent B-lymphotropic gammaherpesvirus. J Immunol. 2000 Feb 15; 164(4):1820-8.
    View in: PubMed
  21. Marshall D, Sealy R, Sangster M, Coleclough C. TH cells primed during influenza virus infection provide help for qualitatively distinct antibody responses to subsequent immunization. J Immunol. 1999 Nov 1; 163(9):4673-82.
    View in: PubMed
  22. Urosevic N, Silvia OJ, Sangster MY, Mansfield JP, Hodgetts SI, Shellam GR. Development and characterization of new flavivirus-resistant mouse strains bearing Flv(r)-like and Flv(mr) alleles from wild or wild-derived mice. J Gen Virol. 1999 Apr; 80 ( Pt 4):897-906.
    View in: PubMed
  23. Moriggl R, Topham DJ, Teglund S, Sexl V, McKay C, Wang D, Hoffmeyer A, van Deursen J, Sangster MY, Bunting KD, Grosveld GC, Ihle JN. Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity. 1999 Feb; 10(2):249-59.
    View in: PubMed
  24. Brown MP, Topham DJ, Sangster MY, Zhao J, Flynn KJ, Surman SL, Woodland DL, Doherty PC, Farr AG, Pattengale PK, Brenner MK. Thymic lymphoproliferative disease after successful correction of CD40 ligand deficiency by gene transfer in mice. Nat Med. 1998 Nov; 4(11):1253-60.
    View in: PubMed
  25. Shellam GR, Sangster MY, Urosevic N. Genetic control of host resistance to flavivirus infection in animals. Rev Sci Tech. 1998 Apr; 17(1):231-48.
    View in: PubMed
  26. Sangster MY, Mackenzie JS, Shellam GR. Genetically determined resistance to flavivirus infection in wild Mus musculus domesticus and other taxonomic groups in the genus Mus. Arch Virol. 1998; 143(4):697-715.
    View in: PubMed
  27. Bunting KD, Sangster MY, Ihle JN, Sorrentino BP. Restoration of lymphocyte function in Janus kinase 3-deficient mice by retroviral-mediated gene transfer. Nat Med. 1998 Jan; 4(1):58-64.
    View in: PubMed
  28. Walker WS, Castrucci MR, Sangster MY, Carson RT, Kawaoka Y. HEL-Flu: an influenza virus containing the hen egg lysozyme epitope recognized by CD4+ T cells from mice transgenic for an alphabeta TCR. J Immunol. 1997 Sep 15; 159(6):2563-6.
    View in: PubMed
  29. Sangster MY, Mo XY, Sealy R, Coleclough C. Matching antibody class with pathogen type and portal of entry: cognate mechanisms regulate local isotype expression patterns in lymph nodes draining the respiratory tract of mice inoculated with respiratory viruses, according to virus replication competence and site of inoculation. J Immunol. 1997 Aug 15; 159(4):1893-902.
    View in: PubMed
  30. Hurwitz JL, Soike KF, Sangster MY, Portner A, Sealy RE, Dawson DH, Coleclough C. Intranasal Sendai virus vaccine protects African green monkeys from infection with human parainfluenza virus-type one. Vaccine. 1997 Apr; 15(5):533-40.
    View in: PubMed
  31. Mo XY, Sangster MY, Tripp RA, Doherty PC. Modification of the Sendai virus-specific antibody and CD8+ T-cell responses in mice homozygous for disruption of the interleukin-4 gene. J Virol. 1997 Mar; 71(3):2518-21.
    View in: PubMed
  32. Mo XY, Tripp RA, Sangster MY, Doherty PC. The cytotoxic T-lymphocyte response to Sendai virus is unimpaired in the absence of gamma interferon. J Virol. 1997 Mar; 71(3):1906-10.
    View in: PubMed
  33. Thierfelder WE, van Deursen JM, Yamamoto K, Tripp RA, Sarawar SR, Carson RT, Sangster MY, Vignali DA, Doherty PC, Grosveld GC, Ihle JN. Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature. 1996 Jul 11; 382(6587):171-4.
    View in: PubMed
  34. Hall RA, Brand TN, Lobigs M, Sangster MY, Howard MJ, Mackenzie JS. Protective immune responses to the E and NS1 proteins of Murray Valley encephalitis virus in hybrids of flavivirus-resistant mice. J Gen Virol. 1996 Jun; 77 ( Pt 6):1287-94.
    View in: PubMed
  35. Shimoda K, van Deursen J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DA, Doherty PC, Grosveld G, Paul WE, Ihle JN. Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature. 1996 Apr 18; 380(6575):630-3.
    View in: PubMed
  36. Topham DJ, Tripp RA, Sarawar SR, Sangster MY, Doherty PC. Immune CD4+ T cells promote the clearance of influenza virus from major histocompatibility complex class II -/- respiratory epithelium. J Virol. 1996 Feb; 70(2):1288-91.
    View in: PubMed
  37. Sangster M, Smith FS, Coleclough C, Hurwitz JL. Human parainfluenza virus type 1 immunization of infant mice protects from subsequent Sendai virus infection. Virology. 1995 Sep 10; 212(1):13-9.
    View in: PubMed
  38. Mo XY, Sangster M, Sarawar S, Coleclough C, Doherty PC. Differential antigen burden modulates the gamma interferon but not the immunoglobulin response in mice that vary in susceptibility to Sendai virus pneumonia. J Virol. 1995 Sep; 69(9):5592-8.
    View in: PubMed
  39. Sangster M, Hyland L, Sealy R, Coleclough C. Distinctive kinetics of the antibody-forming cell response to Sendai virus infection of mice in different anatomical compartments. Virology. 1995 Feb 20; 207(1):287-91.
    View in: PubMed
  40. Hyland L, Sangster M, Sealy R, Coleclough C. Respiratory virus infection of mice provokes a permanent humoral immune response. J Virol. 1994 Sep; 68(9):6083-6.
    View in: PubMed
  41. Sarawar SR, Sangster M, Coffman RL, Doherty PC. Administration of anti-IFN-gamma antibody to beta 2-microglobulin-deficient mice delays influenza virus clearance but does not switch the response to a T helper cell 2 phenotype. J Immunol. 1994 Aug 1; 153(3):1246-53.
    View in: PubMed
  42. Davidson DC, Peart I, Turner S, Sangster M. Prevention with icatibant of anaphylactoid reactions to ACE inhibitor during LDL apheresis. Lancet. 1994 Jun 18; 343(8912):1575.
    View in: PubMed
  43. Sangster MY, Urosevic N, Mansfield JP, Mackenzie JS, Shellam GR. Mapping the Flv locus controlling resistance to flaviviruses on mouse chromosome 5. J Virol. 1994 Jan; 68(1):448-52.
    View in: PubMed
  44. Sangster MY, Heliams DB, MacKenzie JS, Shellam GR. Genetic studies of flavivirus resistance in inbred strains derived from wild mice: evidence for a new resistance allele at the flavivirus resistance locus (Flv). J Virol. 1993 Jan; 67(1):340-7.
    View in: PubMed
  45. Weaver D, Skinner S, Walker L, Sangster M. Phenotypic inhibition of the renin-angiotensin system, emergence of the Ren-2 gene, and adaptive radiation of mice. Gen Comp Endocrinol. 1991 Aug; 83(2):306-15.
    View in: PubMed
  46. Sangster MY, Shellam GR. Genetically controlled resistance to flaviviruses within the house mouse complex of species. Curr Top Microbiol Immunol. 1986; 127:313-8.
    View in: PubMed

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