CROSSTALK BETWEEN INTESTINAL MICROBES, DIET AND MUCOSAL IMMUNITY
IDENTIFY TRIGGERS THAT LEAD TO ABERRANT TYPE 2 IMMUNE-MEDIATED FOOD ALLERGIES
We have shown that enteric reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease (Science, 2017). Loss of oral tolerance to gluten antigen is characterized by proinflammatory T-helper 1 immune responses. However, in contrast to celiac disease, classical food allergies such as peanut allergy for example are initiated via T-helper 2 immune responses going wrong. One aim of my lab is to study and identify triggers that lead to aberrant T-helper 2 immune-mediated food allergies using genetically engineered mouse models, various immunological tools and by collaborating with the food allergy program at the University of Pittsburgh allowing us to translate our findings to human health.
IMPACT OF SOMATIC MUTATIONS ON INTESTINAL BARRIER INTEGRITY
Age-acquired somatic TET2 mutations increase the risk for hematopoietic malignancies. We have shown that microbial signals drive pre-leukemic myeloproliferation in a Tet2-deficient host (Nature, 2018), suggesting new ways of preventing disease development. In this study we have identified that defects in the small intestinal gut barrier lead to systemic bacteria translocation resulting in pre-leukemic myeloproliferation. One aim of my lab is to define the underlying mechanism of this gut barrier defect and to identify potential intestinal abnormalities in humans with somatic TET2 mutations.
INTESTINAL GENE MACHINE
From the very proximal part of the intestine, which is the duodenum, to the very distal part of the colon, this entire organ has highly-specialized site-specific functions and is characterized by differences in the composition of intestinal microbes and host immune cells residing in the epithelium and lamina propria. With the use of next generation sequencing we have identified site-specific genes and want to define their function and relevance under homeostasis and presence of inflammatory triggers using CRISPR-engineered genetically modified mice, organoid co-cultures and various molecular techniques