Welcome to the Villablanca lab
Our lab that lies at the interface of immunology, human health, biological engineering, and systems biology,is seeking to define the complex dynamics of host-environment interactions required to sustain intestinal homeostasis, how breakdown in these interactions may lead to intestinal inflammatory disorders, and how we can promote mucosal healing to reverse the intestinal damage caused by inflammation. The main focus of our lab is to gain insights into the mechanisms that underlie the initiation and resolution of inflammatory bowel disease (IBD) to eventually develop therapeutics to treat intestinal autoimmune diseases.
To accomplish these goals, we have built an interdisciplinary research program that combines the generation of novel experimental models of IBD (zebrafish and mouse),traditional molecular and cellular approaches (e.g. ex vivoimmune cell- intestinal organoid co-culture), cutting-edge technologies (scRNA-seq and spatial transcriptomics), systems biology, and the use of clinical samples. Thus, we are working to provide insights that may lead to novel, rational-based strategies to prevent the initiation of IBD by intervening during its preclinical phase and/or to accelerate and promote tissue regeneration upon damage.
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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.