Carla F. Kim, PhD
Harvard Medical School
The broad interest of our lab is to characterize the biology of stem cells in normal lung and lung cancer. We developed a method to isolate the first stem cell population from the adult murine lung, termed bronchioalveolar stem cells (BASCs). BASCs are critically affected by an oncogenic K-ras mutation and may be the cell-of-origin of lung adenocarcinomas. We will use a combination of mouse genetics, cell biology and genomics approaches to elucidate the biology of these cells during homeostasis and tumorigenesis. An understanding of stem cell functions and regulation in normal lung will be important for innovative approaches to examine the cellular and molecular basis of cancer and diseases that effect lung epithelia as well as serving to identify potential means of early detection and therapy.
Identification and characterization of pulmonary stem cells in vivo
It will be critical to create a system to track the activity of endogenous lung stem cells in vivo. Using knowledge gained from molecular profile studies, we will create genetically engineered mice to determine the lineage relationships that exist between adult lung epithelial cells. These mice will also be useful for studying the mechanisms of lung disease and tumorigenesis.
In addition to understanding lung biology and lung disease, BASCs provide a tool with which to define the mechanisms that control epithelial stem cell self-renewal and lineage-specific differentiation. Expression profiles of BASCs from normal, injured and tumorigenic lung will be used as a platform to identify potential key pathways in stem cells. Complementing gene expression studies, BASC cultures will be placed under renewing or differentiating conditions with a shRNA library to identify genes that are required to direct stem cells. Aside from screens, analysis of candidate pathways regulating stem cells will be directly examined.