Inflammatory bowel disease (IBD) is a debilitating intestinal disorder that imposes substantial physical, psychological, and social burdens on patients, as well as significant economic costs to the healthcare system. Although its precise etiology remains unknown, IBD arises from complex interactions between environmental factors and host genetics. A central determinant in preventing chronic disease is intestinal immune homeostasis—the ability to return to a state of relative quiescence after stress.
A major challenge in the field is understanding how immune signals elicited by the commensal microbiota are regulated to prevent chronic inflammation, while still preserving robust responses to pathogens. The intestinal immune system achieves this balance through multiple regulatory layers. When these mechanisms fail, tonic microbial signals can drive dysregulated innate immune activation and systemic inflammation. Defining the molecular safeguards that preserve this equilibrium is therefore of critical importance.
My laboratory seeks to identify genes that regulate intestinal immune homeostasis and to determine how their disruption contributes to pathologies such as IBD. To this end, we performed a forward genetic screen to identify genes essential for restoring balance within the intestinal immune system. This approach uncovered numerous genes, including those involved in inflammatory signaling, growth factor pathways, and intestinal stem cell proliferation. Unexpectedly, we also identified genes from vesicle trafficking and metabolic pathways.
Goals of the Turer Laboratory
- Unbiased gene discovery: Identify and validate genes essential for maintaining intestinal homeostasis using ENU mutagenesis screens and CRISPR/Cas9 approaches.
- Innate immune regulation: Define the roles of immune signaling pathways in colitis, with a focus on macrophage and dendritic cell biology.
- Epithelial resilience: Elucidate the molecular machinery that maintains the intestinal epithelium during stress and infection.
- Host-microbe interactions: Determine what host factors allow for the maintenance of the intestinal demilitarized zone.
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