DNA variations impact immune host response through the perturbations they cause to transcriptional and biological networks, providing a molecular phenotype* that is an intermediate to the clinical phenotype. By integrating expression quantitative trait loci (eQTLs), gene expression, and clinical data, we are now able to infer transcriptional networks capable of representing causal relationships among genes and traits in the network. This provides the opportunity to identify multiple genetic perturbations that alter the states of molecular networks and that in turn move systems into disease states. Specifically, by dissecting immunogenetic traits, we are able to elucidate key drivers of immune host response beyond what could be achieved by traditional genetic association studies alone. The Systems Immunogenetics core (Core D) will provide critical statistical genetics and computational biology expertise to the U19 investigators across all projects by guiding experimental design with appropriate biostatistical oversight, providing state-of-the-art systems genetics analysis and modeling approaches and ensuring that the vast amounts of data generated are rapidly integrated to identify key genetic regulators of immune phenotype and response to SARS, Influenza and West Nile Viruses.

Public Health Relevance

The Systems Immunogenetics Core provides the blostatistical and computational modeling expertise to elucidate the genetic basis of host immune response and to use this knowledge to aid in prioritization and identification of targets for therapeutic intervention.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Chapel Hill
United States
Zip Code
Gunn, Bronwyn M; Jones, Jennifer E; Shabman, Reed S et al. (2018) Ross River virus envelope glycans contribute to disease through activation of the host complement system. Virology 515:250-260
Kollmus, Heike; Pilzner, Carolin; Leist, Sarah R et al. (2018) Of mice and men: the host response to influenza virus infection. Mamm Genome 29:446-470
Gorman, Matthew J; Caine, Elizabeth A; Zaitsev, Konstantin et al. (2018) An Immunocompetent Mouse Model of Zika Virus Infection. Cell Host Microbe 23:672-685.e6
Baxter, Victoria K; Heise, Mark T (2018) Genetic control of alphavirus pathogenesis. Mamm Genome 29:408-424
Chow, Kwan T; Driscoll, Connor; Loo, Yueh-Ming et al. (2018) IRF5 regulates unique subset of genes in dendritic cells during West Nile virus infection. J Leukoc Biol :
Gralinski, Lisa E; Sheahan, Timothy P; Morrison, Thomas E et al. (2018) Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis. MBio 9:
Menachery, Vineet D; Gralinski, Lisa E; Mitchell, Hugh D et al. (2018) Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines. J Virol 92:
McMullan, Rachel C; Ferris, Martin T; Bell, Timothy A et al. (2018) CC002/Unc females are mouse models of exercise-induced paradoxical fat response. Physiol Rep 6:e13716
Menachery, Vineet D; Schäfer, Alexandra; Burnum-Johnson, Kristin E et al. (2018) MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape. Proc Natl Acad Sci U S A 115:E1012-E1021
Adams Waldorf, Kristina M; Nelson, Branden R; Stencel-Baerenwald, Jennifer E et al. (2018) Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain. Nat Med 24:368-374

Showing the most recent 10 out of 77 publications