Research in the Prows Lab seeks to identify genetic determinants controlling variation in complex human traits by establishing a specific mouse model that captures one or more important features of the human disease. This approach is potentially amenable to any measureable trait of interest, but a primary focus of the lab has been to determine major genetic factors affecting differential susceptibility to acute lung injury (ALI) induced by inhaled oxidants and highly toxic inhaled chemicals (HTICs).
The long-term goals of these projects are to identify key genes and pathological mechanisms critical in the differential pulmonary responses to inhaled toxic agents, and to assess pharmaceutical and/or therapeutic targets for translational studies. To this end, the lab has established several mouse models of oxidant-induced ALI susceptibility, for which an integrative approach of directed breeding, microarray/RNA-Seq expression, and positional candidate gene analyses is being used to identify the major genetic factors affecting differential ALI response. Targeted exome sequencing and resequencing confirmation of top candidate genes will be done to pinpoint the causal gene(s), and follow-up in vitro and in vivo studies will be performed to validate the causal gene(s). Two genetics projects ongoing in the lab utilize continuous hyperoxia (i.e., >95% oxygen; O2) or ozone (O3; 10 ppm) to induce ALI. Many congenic and subcongenic lines of mice have been constructed for both oxidative injuries. Recently, we have proposed extending these mouse models to screen susceptibility differences to other HTICs, including important occupational and environmental agents.