Investigate mechanisms of interferon signaling, gene regulation, and ECM remodeling that control immune cell recruitment.

Epithelium at mucosal layers, such as in the respiratory tract, are primary targets during infections due to their role as barrier cells to the environment and thus have various host defense mechanisms. We need to fully understand the innate immune functions of lung epithelial cells and their role controlling immune cell infiltration and inflammation, an important immune response that needs to be tightly controlled to prevent immune-mediated pathogenesis. Thus, the molecular mechanisms of innate immune cellular signaling pathways and transcriptional regulation and their impact on immune cell recruitment and activation should be investigated.

Systems biology

Predict inflammation using temporal and spatial dynamics of innate immune responses.

With the complexity of the immune system, it is hard to determine the severity of disease that could occur during an immune response. While some inflammatory markers have been identified, more work is needed in determining early signatures that can reliably predict inflammatory responses occurring on a different time scale. Diagnostic markers are often threshold-based and data is captured at a single time point, preventing the use of important dynamic information that can be integral for determining cellular responses. The use of dynamic immune responses would be a good candidate as an early-stage severity of disease marker.

Cellular engineering

Engineer immune cells to promote anti-viral responses.

Consideration of interferons as an effective therapeutic for diseases has been hampered by its adverse side effects (e.g., flu-like symptoms, fatigue) associated with inflammatory cytokines. The current general understanding of interferon treatment and dysregulation that leads to excessive immunopathology is not mechanistic and leads to ineffective and un-targeted therapies. There is a need to develop cellular engineering systems that use interferons. Having an engineered cellular system that promotes controlled IFN-induced anti-viral activity while limiting activation of inflammatory pathways could help prevent immune-related pathogenesis.