Current Research Topics
The general approach of our research is to apply sophisticated mouse modeling with ex vivo crypt manipulations (organoid culture) coupled with high, or super-resolution microscopy and large-scale genomic scans to address the fundamental questions proposed below. Our studies take advantage of our unique ability to engineer cellular changes within the niche and directly examine effects on the stem cells and influences downstream on the niche. By employing both in vivo and ex vivo approaches, we hope to decipher the molecular cues important for intestinal stem cell maintenance and how these cues may go awry in disease states, such as inflammatory bowel disease and cancer.
Lrig1 and Lrig3
Our previous research has shown that Leucine rich repeats and immunoglobulin-like domains 1 (Lrig1), a pan-ErbB negative regulator, marks a distinct population of largely quiescent intestinal stem cells and functions as a growth repressor. These discoveries about the Lrig1+ stem cell population tell us something about the role of the cells within the normal small intestinal and colonic crypts in regulating powerful growth factor signaling cascades, as well as inform us about the potential of both Lrig1 and Lrig3-expressing cells in epithelial repair and regeneration after injury. It is unknown how manipulation of one stem cell population affects the colonic tissue repair process in other stem or progenitor populations.
The enteric nervous system
Research suggests that the enteric nervous system (ENS) acts as a regulator of general gut behavior during inflammation and homeostasis. Although not much is known about the mechanisms behind the ENS-epithelial interaction, our lab examines this through direct imaging of the enteric neurons in mice, which has historically been difficult. Our approach involves visualizing changes in a well characterized GFP-based calcium indicator (GCaMP), which is expressed in neurons of the ENS. Using two-photon microscopy we can detect the fluctuations in fluorescence, which indicates calcium binding during neuronal activation.
The brunner's gland
The Brunner’s gland is found thoughout the small intestine of humans, in the region between the muscle layers and the mucosa. It has long been thought that the gland performs a protective function by producing alkaline mucus secretions in order to neutralize acidic digestive contents passed from the stomach to the duodenum. Additionally, the gland also secretes growth factors. This gland undergoes a tumorigenic transformation in Lrig1 null mice.