Lab Research: Major Areas

Even though designing a preventative CD8 T cell based HIV/SIV vaccine may be extremely challenging, there is reason to believe that acute CD8 T cells may play a role in chronic virus suppression and a functional cure. We are evaluating how CD8 T cells in rhesus macaques and cynomolgus macaques are affected during acute SIV infection and contribute to long term virus suppression. Identifying the most effective functions of each of the different types of CD8 T cells may be key to designing therapeutic interventions for the HIV+ population.

The most common cause of morbidity and mortality in HIV+ individuals is Tuberculosis (TB). Unfortunately, we do not fully understand why HIV+ individuals, even those on HAART, are at such a greater risk for developing active TB disease. We have been working with Dr. Charles Scanga at the University of Pittsburgh to study T cell responses to M. tuberculosis in Mauritian cynomolgus macaques. We mapped epitopes in M. tuberculosis that are restricted by common MHC molecules in these animals to create specific MHC:peptide tetramers. We also found that SIV infection specifically disrupts the ability to mount an effective immune response to M. tuberculosis, leading to more active TB disease. We are now trying to understand the immunological mechanism responsible for the SIV-dependent defects in host immunity to M. tuberculosis in both adult and juvenile macaques. We hope our studies will help define how SIV (as a model for HIV) disrupts host immunity to M. tuberculosis so that interventions can be developed to preserve effective anti-M. tuberculosis immune responses in those infected with immunodeficiency virus.

The development of the tools to molecularly barcode pathogens and then characterize them by deep sequencing has greatly facilitated our ability to study virus and bacterial dynamics upon infection. We are using molecular barcodes for different purposes. We are using barcoded SIV to track the number of infecting viruses in an animal, the selection of escape mutations, and the establishment of the viral reservoir. We are also using a barcoded strain of M. tuberculosis to track dissemination of Mtb in macaques. These tools are used to ask biologically interesting questions, but it requires a specific interest in sequencing pathogens and then the patience and skill to work through bioinformatic analyses to interpret the data.

During the COVID-19 pandemic, we have helped our local community by supporting SARS-CoV-2 surveillance efforts. This included helping to develop a mobile saliva testing program in the summer of 2020, teaching local K-12 nurses how to run antigen tests in late 2020/early 2021, and developing an air surveillance program that routinely detected the Omicron strain in early 2022. We are hoping to continue air surveillance to determine how it can be best used in community settings as a way to forecast virus outbreaks.

Within our lab, we have a Pathogen fee-for-service sequencing unit that is a component of Research Services at the Wisconsin National Primate Research Center. This unit is devoted to sequencing pathogens for clients both at UW and outside of UW. We have sequenced strains of SIV, HIV, Zika, SARS-CoV-2, and other viruses for numerous clients. We sequenced several SARS-CoV-2 stocks that are being used in animal studies at other institutions over the past year. This service unit helps our lab’s sequencing skills continue to grow, lets us collaborate with other researchers, and provide a service to help other investigators.