Hawn, Thomas

We are investigating immunologic mechanisms of disease pathogenesis with an emphasis on genetic, cellular, and molecular studies of the innate immune response. These studies are directed towards understanding why individuals have different susceptibility to infections and whether these insights can lead to novel treatment and vaccine strategies. We are using several approaches to understand this question. First, we are pursuing case-control human genetic studies to find associations of polymorphisms in innate immune response genes with disease susceptibility. Second, we are using ex vivo and in vitro immunologic, cellular and molecular assays to understand how these genes and their variants mediate a protective immune response. Finally, we are complementing these studies with in vivo infection models in mice with targeted gene deletions to elucidate mechanisms of disease pathogenesis. We are using these methods to study the pulmonary innate immune response to Mycobacterium tuberculosis and Legionella pneumophila. In addition, we are examining susceptibility to E. coli and urinary tract infections. We are comparing and contrasting the host immune response to these different pathogens to gain a better understanding of immunogenetics and human susceptibility to infections.

Hayashi, F, Smith, KD, Ozinsky, A., Hawn, TR, Yi, EC, Goodlett, DR, Eng, JK, Akira, S, Underhill, DM, Aderem, A. (2001) The innate immune response to bacterial flagellin is mediated by toll-like receptor-5. Nature 410: 1099-1103.

Hawn, TR, Verbon, A, Lettinga, KD, Zhao, LP, Li, SS, Laws, RJ, Skerrett, SJ, Beutler, B, Schroeder, L, Nachman, A, Ozinsky, A, Smith, KD, Aderem, A. (2003) A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to Legionnaires’ Disease. J. Exp Med. 198: 1563-1572.

Hawn, TR, Verbon, A, Janer, M, Zhao, LP, Beutler, B, Aderem, A. (2005) TLR4 polymorphisms are associated with resistance to Legionnaires’ Disease. Proc. Nat. Acad. Sci. 102: 2487-89.

Hawn, TR, Wu, H, Grossman, JM, Hahn, BH, Tsao, BP, Aderem, A. (2005) A TLR5 stop codon polymorphism is associated with resistance to systemic lupus erythematosus. Proc. Nat. Acad. Sci. 102: 10593-7.

Hawn, TR, Smith, KD, Aderem, A, Skerrett, SJ. (2006) MyD88-/- and TLR2-/- mice are susceptible to infection with aerosolized Legionella pneumophila. J. Inf Dis. 193: 1693-1702.

Hawn, TR, Dunstan, SJ, Thwaites, GE, Simmons, CP, Nguyen, TT, Nguyen, TNL, Quy, HT, Chau, TTH, Rodrigues, S, Janer, M, Zhao, LP, Hien, TT, Farrar, JJ, Aderem, A. (2006) A polymorphism in human TIRAP is associated with susceptibility to meningeal tuberculosis. J. Inf. Dis. 194: 1127-34.

Hawn, TR, Misch, EA, Dunstan, SJ, Thwaites, GE, Lan, NTN, Quy, HT, Chau, TTH, Rodrigues, S, Nachman, A, Janer, M, Hien, TT, Farrar, JJ, Aderem, A. (2007) A common human TLR1 polymorphism regulates the innate immune response to lipopeptides. Eur. J. Immunol. 37: 2280-89.

Berrington, WR, Hawn, TR. (2007) Mycobacterium tuberculosis, macrophages, and the innate immune response: does common variation matter? Immunological Reviews. 219: 167-86.