Research Summary

Functional interrogation of interferon lambda 4 (IFN-L4) in human health and disease

The broader question I seek to answer in this project is: What is the function of IFN-λ4 in human health and disease. In this proposal I am interested to better define the functions of IFN-λ4 as an immunomodulatory cytokine, and seek to answer the questions: what other cellular proteins it interacts with? How does the potential to express a functional IFN-λ4 affect the basal antiviral states in healthy individuals? What is the molecular mechanism behind the association of the functional IFN-λ4-generating polymorphism with allergic asthma? Does the potential to express a functional IFN-λ4 associate with a less severe dengue disease?

The answers to these questions are important to know since human IFN-λ4 is an important and potent antiviral cytokine that is expressed in only a subset of the individuals in any given population. It is expressed out of a frame-shift causing genetic polymorphism that varies in allele frequency based on ethnicity. Its expression is the highest in people of African ancestry, intermediate in the European population and the least in the east-Asian population. Potential to express a functional IFN-λ4 is known to be detrimental in some instances (like hepatitis C virus infections) but beneficial in others (like inflammatory conditions). Defining its functions will allow us to understand several disease and health conditions in humans that the IFN-λ4-generating polymorphism is associated with.