Our Research
The stomach and intestine are ideal organs to investigate processes of fundamental biomedical interest:
This is because the digestive tract develops early in embryos, with a large mass that reflects inductive interactions between the embryonic endoderm and splanchnic mesoderm. After birth, the organ is readily accessible, with an abundance of self-renewing stem and progenitor cells. The progeny of these cells replace the epithelial lining every few days, and well-defined microscopic anatomy allows this process to be monitored in detail.
Our laboratory takes advantage of these features to study molecular mechanisms of gut development and tissue differentiation, particularly the transcriptional and chromatin basis for cell diversity in response to local signals. Our research combines mouse genetics with molecular, developmental, cell, and computational biology.
The intestinal epithelium is also the origin of colorectal cancer, the second leading cause of cancer death in the West (~50,000 deaths annually in the US). A refined appreciation of the developmental and stem-cell underpinnings of the normal epithelium will serve as a foundation for future rational preventive and treatment strategies.
Background: The digestive tract develops as a result of interactions between cells derived from the embryonic endodermal and mesodermal germ layers. The endoderm gives rise to the digestive epithelia, while adjacent mesoderm produces mesenchyme and smooth muscle. To understand the cellular and molecular basis of gut development, we study the differentiation and patterning of fetal endoderm into gut-specific epithelia, and how the esophagus and stomach acquire structure and properties distinct from those of the intestine.
After birth, the stomach and intestine develop distinct epithelial compartments that house long-lived stem and short-lived progenitors. These cells have an enormous capacity for self-renewal and differentiate briskly into the resident epithelial cell types: absorptive and secretory cells in the intestine, and various types of secretory cells in the stomach. To better understand stem cell properties and their determinants, we study selected transcription factor responses to local signals (such as Wnt, Hedgehog, Notch and Bone Morphogenetic Proteins, BMPs) and the native chromatin environment in crafting tissue-specific gene expression.
The overarching goal of the laboratory is to understand how these processes influence and mold each other in development, homeostasis, and cancer.
- Self-renewal of adult tissues
- Properties of progenitor and stem cells
- Tissue-specific gene regulation
- Inductive tissue interactions in embryos and adults
- The nexus of signaling and transcriptional control mechanisms
This is because the digestive tract develops early in embryos, with a large mass that reflects inductive interactions between the embryonic endoderm and splanchnic mesoderm. After birth, the organ is readily accessible, with an abundance of self-renewing stem and progenitor cells. The progeny of these cells replace the epithelial lining every few days, and well-defined microscopic anatomy allows this process to be monitored in detail.
Our laboratory takes advantage of these features to study molecular mechanisms of gut development and tissue differentiation, particularly the transcriptional and chromatin basis for cell diversity in response to local signals. Our research combines mouse genetics with molecular, developmental, cell, and computational biology.
The intestinal epithelium is also the origin of colorectal cancer, the second leading cause of cancer death in the West (~50,000 deaths annually in the US). A refined appreciation of the developmental and stem-cell underpinnings of the normal epithelium will serve as a foundation for future rational preventive and treatment strategies.
Background: The digestive tract develops as a result of interactions between cells derived from the embryonic endodermal and mesodermal germ layers. The endoderm gives rise to the digestive epithelia, while adjacent mesoderm produces mesenchyme and smooth muscle. To understand the cellular and molecular basis of gut development, we study the differentiation and patterning of fetal endoderm into gut-specific epithelia, and how the esophagus and stomach acquire structure and properties distinct from those of the intestine.
After birth, the stomach and intestine develop distinct epithelial compartments that house long-lived stem and short-lived progenitors. These cells have an enormous capacity for self-renewal and differentiate briskly into the resident epithelial cell types: absorptive and secretory cells in the intestine, and various types of secretory cells in the stomach. To better understand stem cell properties and their determinants, we study selected transcription factor responses to local signals (such as Wnt, Hedgehog, Notch and Bone Morphogenetic Proteins, BMPs) and the native chromatin environment in crafting tissue-specific gene expression.
The overarching goal of the laboratory is to understand how these processes influence and mold each other in development, homeostasis, and cancer.