Areas of Research
- Lung Development
- Single-Cell Genomics
- Cell Signaling
We have a cell-centric view of biology and are interested in three aspects of cells: (1) cell behavior, such as morphology and turnover; (2) cell lineage, such as differentiation and conversion; (3) cell signaling, such as paracrine and juxtacrine. We use the mouse lung as our model system and study how the lung is built during development and how it is repair upon injury.
One focus of the lab is on the lung epithelial progenitors and how they maintain the lung fate and orderly differentiate into airway and alveolar
cells. We are dissecting the epigenetic mechanism and testing its relevance in regenerative medicine using lung cells derived from human embryonic stem cells.
A second focus of the lab is on the alveolar type 1 (AT1) cells, which are individually >10,000 um2 in surface area and together constitute 95% of the gas exchange epithelium, but are merely 0.1 um thick to allow passive gas diffusion. My lab focuses on these extremely specialized AT1 cells – as human geneticists focus on rare inherited diseases – due to their large effect size.
(1) We are dissecting the transcriptional network underlying AT1 cell specification and specifically how the lung lineage transcription factor NKX2-1 controls cell-type-specific epigenomes.
(2) We are pursuing the subcellular machinery driving the expansive, ultrathin morphology of AT1 cells. We are building Cre-dependent reporter mice to visualize in high resolution and in real time microtubule and actin cytoskeletons, focal adhesions, adherens junctions, lysosomes, and mitochondria in any cell type of choice.
(3) We have shown that AT1 cells are not just a passive structural component, but also have signaling roles toward endothelial cells and fibroblasts, which leads to our discovery of a new endothelial cell type that we consider the equivalent of tip cells during sprouting angiogenesis.
(4) We are extending our insights of AT1 cells during development and homeostasis to injury-repair.
(5) Finally, we are taking a cross-species genomic and genetic approach to dissect the molecular events underlying lung evolution.
We approach these questions on the level of individual cells using precision mouse genetics, single-cell genomics, and three-dimensional imaging and expect our work to provide insights into lung immaturity in preemies and pulmonary hypertension.
The Chen Laboratory
MD Anderson Cancer Center
6565 MD Anderson Blvd., Zayed Building
Houston, Texas 77030