Jakob von Moltke, PhD (Immunology)
Our lab studies immune responses to parasitic worms (helminths) and allergens. Remarkably, despite being enormously diverse, helminths and allergens all give rise to a “type 2” immune response that is characterized by profound changes in tissue physiology such as increased mucus production (runny nose) and hypercontractility of smooth muscle (coughing/sneezing). Although these clinical manifestations of type 2 immunity are well known, some of the most fundamental questions about how type 2 immunity is first activated remain unanswered. Indeed, we do not even know how the immune system first senses the presence of helminths and allergens. Therefore, our recent discovery that specialized cells in the intestinal lining called tuft cells are required for initiation of type 2 immunity provided an exciting advance. Notably, the number of tuft cells in the intestine increases enormously during helminth infection and we have shown that this requires reprogramming of stem cells to bias them towards production of tuft cells.
Although they were discovered more than 50 years ago, the function of tuft cells remained unknown. We believe tuft cells are ideally positioned to both sense worms and transmit signals to the immune system and we are using genetic mouse models combined with microscopy, single cell analysis, and specialized tissue culture to study the underlying mechanisms. We are also particularly interested in how signals from the immune system shape the fate decisions of non-immune stem cells. Although helminths provide a useful model for scientific inquiry, we believe our findings will provide insight into the immune pathways underlying allergic disease and could suggest novel therapeutic targets for treating both helminth infection and allergies.