 |
|
|
|
 |
|
|
|
|
|
|
Department
|
Stem Cell Program
Department of Medicine
Division of Hematology/Oncology
|
|
Hospital Title
|
Principal Faculty, Stem Cell Program
|
|
Academic Title
|
Assistant Professor
|
|
Phone
|
617-919-4644
|
|
Fax
|
617-730-0222
|
|
Email
|
Carla Kim
|
|
Location
|
300 Longwood Avenue
Boston MA 02118
|
 |
 |
|
|
|
|
|
|
|
The broad interest of the Kim Lab is to characterize the biology of stem cells in normal lung and lung cancer. Numerous lung diseases such as cystic fibrosis or chronic obstructive pulmonary disease involve injured or depleted bronchiolar or alveolar epithelium. Bronchiolar and alveolar cells are also affected in adenocarcinoma, the most common form of lung cancer. It is likely that lung stem cells are critically affected in patients with these devastating diseases. The lab's long-term goal is to elucidate the role of stem cells in lung homeostasis as a prerequisite to the development of therapeutic strategies that can be used to prevent or attenuate lung disease.
Dr. Kim and her colleagues isolated 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. They hypothesize that BASCs are the stem cells that maintain bronchiolar and alveolar cell homeostasis in vivo. They use a combination of mouse genetics, cell biology and genomics approaches to elucidate the biology of these cells during homeostasis and tumorigenesis.
The current experimental focus of the Kim Lab is to test the potential of BASCs in vivo. Expanding on work showing that BASCs are multipotent in culture, it will be important to determine the potential of isolated BASCs to produce lung epithelial cells in animal models. However, lack of functional tests for lung stem cells precludes understanding the role of BASCs in the mechanisms of lung disease as well as their potential beneficial uses. Therefore, they are developing transplantation methods to determine if BASCs can give rise to bronchiolar and alveolar cells in vivo. Complementing a transplantation assay, lineage tracing will be performed to assess the potency of BASCs without removing them from the lung. They are currently creating the knock-in mice and other tools necessary to perform lineage tracing in the adult lung in vivo. Finally, they are also using preclinical models of lung injury and lung cancer to elucidate how lung disease impacts lung stem cell function. Their work will provide the foundation required for innovative approaches to examine the cellular and molecular basis of cancer and other diseases that effect lung epithelia as well as serving to identify potential means of early detection and therapy.
|
|
|
|
|
|
Carla Kim is interested in the relationships between stem cell biology, cancer biology, and lung biology. She earned her PhD in Genetics at the University of Wisconsin, Madison. As a graduate student in the laboratory of John Petrini, she studied the role of the Rad50 gene in DNA damage responses and homeostasis in vivo. She found that a point mutation in the murine Rad50 gene led to bone marrow failure (likely due to hematopoietic stem cell failure) as well as increased suseptibility to hematopoietic malignancy. These studies stimulated her interest in determining if stem cells played a role in the initiation of cancer. She went on to a postdoctoral position in the laboratory of Tyler Jacks at the Massachusetts Institute of Technology Center for Cancer Research. There, she developed a method to isolate the first stem cell population from the adult murine lung, termed bronchioalveolar stem cells (BASCs). She also showed that BASCs are critically affected by an oncogenic K-ras mutation and may be the cell-of-origin of lung adenocarcinomas.
|
|
|
|
|
- Kim CF. Paving the road for lung stem cell biology: bronchioalveolar stem cells and other putative distal lung stem cells. Am J Physiol Lung Cell Mol Physiol. 2007; 296:L1092-8.
- Kim CFB, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, Crowley D, Bronson RT, Jacks T. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005;121:823-35.
- H J, Houghton AM, Mariani TJ, Perera S, Kim CB, Padera R, Tonon G, McNamara K, Marconcini LA, Hezel A, El-Bardeesy N, Bronson RT, Sugarbaker D, Maser RS, Shapiro SD, Wong KK. K-ras activation generates an inflammatory response in lung tumors. Oncogene 2006;25:2105-12.
- Kim, CFB, Jackson EL, Kirsch DG, Grimm J, Shaw AT, Lane K, Kissil J, Olive KP, Sweet-Cordero A, Weissleder, Jacks T. Mouse models of human non-small-cell lung cancer: raising the bar. Cold Spring Harbor Symposia on Quantitative Biology, 2005, Volume LXX:241-250.
- Kim, CFB. Advancing the field of lung stem cell biology. Frontiers in Bioscience 2007;12:3117-3124.
|
|
|
|
|
|
|
|
|
|
|
