Emory Vaccine Center, 954 Gatewood Rd.
ATLANTA, GA 30329
404 727-8945 Phone
BA (Honors) Cambridge University, Queens' College, 1985 - 1988
Ph.D. The Walter & Eliza Hall Institute for Medical Research
TheUniversity of Melbourne, 1991 - 1995
In many ways the immune system can be described in anthropomorphic terms: it's memory allows it to remember and recognize pathogens, commensals or vaccines, after years or even decades; it can distinguish between the body's own cells and those of another organism; and it makes decisions about how to respond to particular pathogens. This last characteristic is the focus of our research. Central to the immune system's decision-making process are dendritic cells (DCs), which can sense pathogens, commensals, or vaccines, and orchestrate appropriate immune responses to them. Given their emergence as key regulators of the immune response, there is great enthusiasm for harnessing DCs in the immune therapy of infectious diseases, autoimmunity, allergies, transplantation and cancer [e.g. Pulendran & Ahmed, 2006, Cell. 124: 849; Pulendran, 2004, Immunol. Reviews. 199: 227; Pulendran et al, 2001, Science. 293: 253]. Our research is focused on understanding the fundamental mechanisms by which DCs control innate and adaptive immune responses, as well as in exploiting these in vaccinology and immune therapy. Within this board area, our specific goals are:
1. To determine the molecular mechanisms and signaling networks by which different microbial stimuli modulate DC function so as to induce strikingly different classes of adaptive immune responses [Th1, Th2, Th17, tolerogenic, or T regulatory responses]. Recent data from our lab suggest that the nature of the particular subset of DC, as well as the type of pathogen recognition receptors (e.g. Toll receptors, C-type lectins) expressed by the DCs play important roles in this process [Agrawal et al, 2003, Cutting Edge: J. Immunol 171: 4984; Dillon et al, 2004, J. Immunol. 172: 2797; Dillon et al, 2006, J. Clin Invest. 116: 916]. This question is being further explored using a combination of cellular and molecular immunological techniques, including transgenic and knockout mice, gene array and proteomic technologies, and in vivo models of immune response, using both mice and non-human primates.
2. To study how different pathogens, including certain agents of bioterrorism such as anthrax and Ebola, modulate DC function during pathogenesis. These projects are being pursued in collaboration with scientists at the Centers for Disease Control (CDC) [Agrawal et al, 2003, Nature. 424:329; Mahanty et al, 2002; Cutting Edge, J. Immunol. 170:2797].
3. To understand the immunological mechanisms by which some of our best empirically derived vaccines work, with a view to utilizing such insights in the design of novel vaccines against pandemics and emerging infections. To this end, our recent work suggests that the highly successful yellow fever vaccine 17D (YF-17D), an empirically derived vaccine which has been administered to over 400 million people over the past 65 years, works by stimulating multiple Toll-like receptors on several different subsets of DCs, to evoke a broad spectrum of adaptive immune responses [Querec et al, 2006, J. Exp. Med. 203: 413]. We are presently undertaking a systems biological approach, using genomics and proteomics, to determine whether there are "signatures" of early innate immune activation, which could predict the magnitude, quality and persistence of the immune response in humans vaccinated with YF-17D.
4. To utilize insights gained above to develop novel vaccines. In this context, an ongoing project aims to explore the efficacy of using TLR ligands and other agents that modulate DC numbers (e.g. Flt3-Ligand) or function, as immune modulators or vaccine adjuvants against HIV, in non human primate models.
Reviewer for Cell, Nature, Science, Nature Immunol, Nature Medicine, Nature Reviews Immunology, J. Exp. Med, J. Immunol, Immunity, Blood, Trends in Immunology, Virology, International Immunology, European Journal of Immunology, Journal of Clinical Investigation,
Co-Chair of the Scientific Working Group on Systems Biology in HIV Vaccine Development, Global Vaccine Enterprise, 2009 - present
MERIT AWARD from NIAID, National Institutes of Health, 2009 - 2019
Member of the AIDS Vaccine Research Subcommittee, NIAID, NIH, 2008 - present
Editorial Board, The Journal of Clinical Investigation, 2008 - present
Elected Member of the Collegium Internationale Allergologicum, 2007 - present
Scientific Advisory Board, Juvaris Biotherapeutics, 2007 - present
Scientific Leadership Group of consortium funded by the Bill & Melinda Gates Foundation to harness innate immunity to combat HIV, 2006 - present
Section Editor of The Journal of Immunology, 2005 - 2009
Invited Member on the Expert Panel on Innate Immunity, Defense Threat Reduction Agency, 2005
Member of Innate Immunity & Inflammation study section, 2004-2007
Associate Editor of The Journal of Immunology, 2004-2005
Member of the Experimental Immunology Study Section, NIAID, 2002-2004
Invited Member on the Expert Panel on Bioterrorism, NIAID, 2002
Chakraborty R, Pulendran B. Restraining order for dendritic cells: all quiet on the fetal front. J Clin Invest;119(7):1854-7.
Querec TD, Akondy RS, Lee EK, Cao W, Nakaya HI, Teuwen D, Pirani A, Gernert K, Deng J, Marzolf B, Kennedy K, Wu H, Bennouna S, Oluoch H, Miller J, Vencio RZ, Mulligan M, Aderem A, Ahmed R, Pulendran B. (2009). Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol. 10(1):116-25. Epub 2008 Nov 23.
Manicassamy S, Ravindran R, Deng J, Oluoch H, Denning TL, Kasturi SP, Rosenthal KM, Evavold BD, Pulendran B. (2009). Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity. Nat Med. 15(4):401-9. Epub 2009 Mar 1.
Kasturi SP, Pulendran B. (2008). Cross-presentation: avoiding trafficking chaos? Nat Immunol. 9(5):461-3.
Pulendran B, Cao W. (2008). 2008 A MyD88 O, DC. Immunity;29(2):173-5.
Pulendran B, Miller J, Querec TD, Akondy R, Moseley N, Laur O, Glidewell J, Monson N, Zhu T, Zhu H, Staprans S, Lee D, Brinton MA, Perelygin AA, Vellozzi C, Brachman P Jr, Lalor S, Teuwen D, Eidex RB, Cetron M, Priddy F, del Rio C, Altman J, Ahmed R. (2008). Case of yellow fever vaccine--associated viscerotropic disease with prolonged viremia, robust adaptive immune responses, and polymorphisms in CCR5 and RANTES genes. J Infect Dis;198(4):500-7.
Pulendran B, Ono SJ. (2008). A shot in the arm for mast cells. Nat Med. 14(5):489-90.
Cao W, Manicassamy S, Tang H, Kasturi SP, Pirani A, Murthy N, Pulendran B. (2008). Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway. Nat Immunol. 9(10):1157-64. Epub 2008 Aug 31.
Gururajan M, Jacob J, Pulendran B. (2007). Toll-like receptor expression and responsiveness of distinct murine splenic and mucosal B-cell subsets. PLoS One;2(9):e863.
Denning TL, Wang YC, Patel SR, Williams IR, Pulendran B.(2007). Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat Immunol;8(10):1086-94. Epub 2007 Sep 16.
Pulendran, B. (2006). Division of labor and cooperation between dendritic cells. Nat Immunol;7(7):699-700
Querec T, Bennouna S, Alkan S, Laouar Y, Gorden K, Flavell R, Akira S, Ahmed R, Pulendran B. (2006). Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. J Exp Med. 203(2):413-24.
Dillon S, Agrawal S, Banerjee K, Letterio J, Denning TL, Oswald-Richter K, Kasprowicz DJ, Kellar K, Pare J, van Dyke T, Ziegler S, Unutmaz D, Pulendran B. (2006). Induction of tolerogenic T cells by dectin mediated triggering of ERK in DCs. J Clin Invest. 116(4):916-28.
Pulendran, B., Ahmed, R. (2006). Translating innate immunity into long term T and B cell memory: implications for vaccine development. Cell.124:849-863.
Dillon S, Agrawal A, Van Dyke T, Maliszewski C, Akira S, & Pulendran, B. (2004). A TLR 2 ligand stimulates Th2 responses in vivo, via induction of ERK MAP kinase and c-Fos in dendritic cells. J .Immunol. 172(8):4733-43.
Pulendran, B. (2004). Modulating vaccine responses with dendritic cells and Toll-like receptors. Immunological Reviews. 199:227-50.
Agrawal A, Lingappa J, Jabbar A, Agrawal S, Leppla S, Quinn C, Pulendran B. (2003). Impairment of dendritic cells and adaptive immunity, by anthrax toxin, lethal factor. Nature. 424(6946):329-34.
Mahanty S., Hutchison, K., Agrawal, S., Rollin, PE.,Pulendran, B. Impairment of Dendritic Cellls and Adaptive Immunity by Ebola and Lassa viruses Cutting Edge: J. Immunol. 170(6):2797-801.
Agrawal S, Agrawal A, Doughty B, Van Dyke T, Gewirtz A, Pulendran B. (2003). Different TLR agonists instruct dendritic cells to induce distinct T-helper responses, via differential modulation of ERK MAP kinase and c-Fos. Cutting Edge: J. Immunol 171(10):4984-9.
Pulendran, B., Kumar, P., Cutler, C., Mohamadzadeh, M., Maliszewski, C; Davoust, J.,& Banchereau, J. LPS from distinct microbes elicit distinct classes of immune responses in vivo. (2001). J. Immunol. 167(9): 5067-76.
Pulendran, B., Palucka, K & Banchereau, J. (2001). Sensing Pathogens and Tuning Immune Responses. Science 293(5528): 253-6.
Pulendran B, Maraskovsky E, Banchereau J & Maliszewski C. (2001). Th1/Th2 regulation by dendritic cell subsets. (2001). Trends in Immunology. 22(1): 41-47.
Banchereau, J., Pulendran, B., Steinman, R., & Palucka, K. (2000). Will the making of plasmacytoid dendritic cells in vitro help unravel their mysteries? J. Exp. Med. 192(12) F39-44.
Banchereau J., Briere F., Caux C., Davoust J., Lebecque S., Liu Y-J. (2000). Pulendran B., & Palucka K. Immunobiology of Dendritic Cells Ann. Review of Immunology. 18: 767-811.
Pulendran B., Burkeholder S., Kraus E., Guinet E., Fay J., Davoust J., Maliszewski C., Banchreau J.,& Palucka K.(2000). Differential mobilization of distinct human DC subsets in vivo by Flt3-Ligand and G-CSF J. Immunol. 2000 165(1): 566-72.
Pulendran B, J.L.Smith, G.Caspary, K. Brasel, D. Pettit, Maraskovsky & C. Maliszewski (1999). Distinct dendritic cell subsets differentially regulate the class of immune responses in vivo Proc. Natl. Acad. Sci. USA 96, 1036-1041
Pulendran B, J.L. Smith, M. Jenkins, M. Schoenborn, E. Maraskovsky, and C.R. Maliszewski. (1998). Prevention of peripheral tolerance by a dendritic cell growth factor: flt3 ligand as an adjuvant. J Exp Med. 188(11):2075-82.
Pulendran B, J. Lingappa, M. K. Kennedy, J. Smith, M. Teepe, A. Rudensky, C. R. Maliszewski & E. Maraskovsky (1997). Maturation pathways of dendritic cells in vivo: distinct function, phenotype and localization of lymphoid and myeloid dendritic cell subsets in Flt3-L treated mice J. Immunol. 159: 2222-2231.
Pulendran B, Kannourakis G, Nouri S, Smith KGC, Nossal, GJV (1995). Soluble antigen can cause apoptosis of germinal center B cells. Nature 375:331-334.
Pulendran B, Karvelas M, Nossal GJV (1994). A form of immunologic tolerance through impairment of germinal centers. Proc Natl Acad Sci USA 91: 2639-2643.