Daniel E. Hassett
Assistant Professor

hassettd@missouri.edu

Research emphasis: Modulation of immune responses to infectious diseases and vaccines during pregnancy and early in life, cell mediated immunity and immunology of reproduction.

Dr. Hassett’s research focuses on the mechanisms of cell mediated immunity in neonates and pregnant women during the course of infections and in response to anti-microbial vaccines. Pregnancy and the neonatal period produce a transient state of immune suppression that is characterized by decreased ability to mount effective cell-mediated immune responses. We are also interested in learning how the physiology of the placenta changes when it is infected with intracellular pathogens. Studies in the laboratory investigate the pathophysiological effects of infection with Lymphocytic Choriomeningitis virus (LCMV), Vaccinia virus and Ectromelia virus in pregnant and neonatal mice. Primary infections with LCMV in pregnant mice and women cause limited maternal disease but high prenatal mortality from disruption of placental function and/or active infection of the fetus. Immunizing a pregnant mouse or woman with vaccinia virus during pregnancy can cause a fatal infection of the developing fetus. The fundamental mechanisms involved in fetal infection are unknown. Pathogen-specific CD8+ and CD4+ T cells participate in the resolution of these infections in vivo and provide resistance to re-infection. However, our data with LCMV indicate that T cells fail to adequately clear these organisms from the uterus and placenta. We are determining what cell types are infected in vivo and whether the placenta inhibits the induction of pro-inflammatory cytokines and chemokines. We are using biochemical and flow cytometric approaches to study the effector functions of T cells induced by infection or vaccination early in pregnancy and the neonatal period. Our goals are to understand how these physiological states impact on the ability of the immune system to mount effective antiviral defenses and to facilitate the development of improved vaccines specifically tailored to the unique needs of mothers and infants.

Teaching: Immunology and Introduction to Research Ethics

Selected publications:

Benning, N. and D.E. Hassett. 2004 Vaccinia virus infection during murine pregnancy, a new pathogenesis model for vaccinia fetalis. J. Virol. 78(6):3133-3139.

Hassett, D.E. 2003. Smallpox infection during pregnancy, lessons on pathogenesis from nonpregnant animal models of infection J. Reprod. Imm. 60(1): 13-24.

Zhang, J., Silvestri, N., J.L. Whitton and D.E. Hassett. 2002 Neonates mount robust and protective adult-like CD8+ T cell responses to DNA vaccines. J. Virol. 76: 11911-11919.

Hassett, D.E., J. Zhang, M. Slifka and J.L. Whitton. 2000. Immune responses following neonatal DNA vaccination are long-lived, abundant, and qualitatively similar to those induced by conventional immunization. J. Virol. 74: 2620-2627.

Meharra, E. J., M. Schon, D. Hassett, C. Parker, W. Havran and H. Gardner. 2000. Reduced gut intraepithelial lymphocytes in VLA1 null mice. Cell. Immunol. 201(1):1-5.

Hassett, D.E., M.K. Slifka, J. Zhang and J.L. Whitton. 2000. Direct ex vivo kinetic and phenotypic analyses of CD8+ T cell responses induced by DNA immunization. J. Virol. 74: 8286-8291.

Hassett, D.E., J. Zhang, and J.L. Whitton. 1999. Plasmid DNA vaccines are effective in the absence of IFN?. Virology. 263: 175-183.