Current Projects
Cross Reactive T cells: Future vaccines are being designed to protect against multiple members of the same viral family. The idea behind these “pan-family” vaccines is to incorporate antigens shared between pathogens of a viral family. The idea is that shared antigens can induce cross-reactive immune responses that protect against multiple pathogens from the same family. To understand how cross-reactive T-cell responses develop and their role in controlling viral infection, my laboratory uses small animal models infected with multiple pathogens and monitors both the virus-specific and cross-reactive T-cell responses. We have identified differences in both viral clearance and effector function of cross-reactive T cells compared to their non-cross-reactive counterparts. We are currently working to understand the molecular mechanisms which drive these differences.
Obesity and T cell immune dysfunction Numerous comorbidities have been associated with obesity, including immune cell dysfunction. Following the 2009 H1N1 pandemic, obesity was published as an independent risk factor that could predict severe infection outcomes. The goal of our studies is to determine if obesity alters immune responses to viruses and vaccines and, if so, to determine the mechanism by which this occurs.
Viral sepsis is a preventable cause of morbidity and mortality. Anyone can develop sepsis regardless of age or health status. Sepsis is caused by a dysregulation of the host's response to a pathogen. One-third of those who develop sepsis die, and those that survive are left with chronic debilitating conditions. While bacterial pathogens cause a large majority of cases of sepsis, over 30 percent of sepsis cases are not bacterial in origin, and antibiotic treatments are the only current treatment for sepsis. One factor often overlooked in our response to sepsis is that the diseases have striking similarities. By focusing on the similarities between diseases, we can rapidly target infection symptoms and independently of a disease diagnosis. “Cytokine storm” is one of the most notable characteristics of sepsis and can last for several hours or a few days. The cytokine-mediated inflammation along with complement activation increases vascular permeability, causes hemorrhaging, and is responsible for the organ damage associated with surviving sepsis. In the case of viral sepsis in humans, viral suppression of the type I interferon (IFN) signaling pathway is thought to be a significant contributor to the initiation of sepsis. How inhibition of type I IFN signaling contributes to sepsis is an area of active investigation in my laboratory.
Correlates of protection for emerging pathogens. We use small animal models to elucidate cell-mediated mechanisms of virus infection control and evaluate the generation of innate and protective adaptive immune responses to novel emerging pathogens. Through this work, we have identified critical mechanisms by which T cells are programmed to recognize virally encoded antigens and mechanisms of viral clearance. These studies provide fundamental insights into the protective capacity of T cells.
SARS-CoV-2 Projects
Early during the pandemic, we identified the murine T cell epitopes for SARS-CoV-2 (Hassert PlosPath 2020). We have used this information to study the immune response to SARS-CoV-2 in our obesity model, to understand the link between severe COVID-19 and obesity. We have also started to look at the cross-reactive T cell responses between SARS-CoV-2 and the human coronaviruses. Our work with SARS-CoV-2 has resulted in five contributing author publications and more importantly the establishment of strong collaborations with some brilliant scientists around the world.