In our latest publication, we used longitudinal colon gene expression analysis from the acute epithelial injury and recovery phases of DSS colitis in mice, to inform molecular classification of Ulcerative Colitis (UC) patients. In particular, we showed that conserved inflammatory genes largely involved in neutrophil and monocyte/macrophage function enable a stable classification of two sub-types of ulcerative colitis (UC) in humans, which we called UC1 and UC2. A careful time series of colon inflammation and repair following DSS administration to mice revealed specific inflammatory, epithelial repair, and metabolic modules during the different stages of disease in mice, some of which were conserved in humans. The UC1 subgroup is characterized by an enhanced neutrophil inflammatory gene module and poor response to biological treatments. We have mapped these temporal data from the murine model to human risk genes, providing potential insight into their role in UC pathogenesis.Thus, our observation on differential responsiveness of the UC1 and UC2 subgroups demonstrate that our descriptive study of gene expression in mouse has led to meaningful insight into the use of gene expression to classify responders and non-responders to therapy and indicates the potential of this approach. This can be used for any autoimmune disease in which there is an existing experimental study.
Kumar Parijat Tripathi
Visiting PhD Student (2018-2019)