Carla Kim, PhD

 

Research Overview

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 Kim Lab is now focused on two major questions involving lung stem cells. First, they have created important tools to test the potential of BASCs. Expanding on work showing that BASCs are multipotent in standard culture conditions, it will be important to determine the potential of isolated BASCs to produce lung epithelial cells in animal models. They have developed unique three-dimensional culture systems and transplantation methods to show if BASCs can give rise to bronchiolar and alveolar cells. Complementing a transplantation assay, lineage tracing is being performed to assess the potency of BASCs without removing them from the lung. Secondly, they are also using preclinical models of lung injury and lung cancer to elucidate how lung disease impacts lung stem cell function in human and murine samples. 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.

About Carla Kim

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. 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. In addition to her work at Children’s Hospital and Harvard Medical School, Dr. Kim is a principal faculty and executive committee member of the Harvard Stem Cell Institute. She is also a member of the Lung Cancer Program at the Dana Farber/Havard Cancer Center Lung Cancer Program. For more information on Dr. Kim, her lab and their research, please go to http://kim.tchlab.org/index.htm.

Key Publications

• Tropea K, Leder E, Aslam M, Lau A, Raiser D, Lee J, Balasubramaniam V, Frendenburgh L, Mitsialis S, Kourembanas S, Kim CF. (2012) Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol, 302(9):L829-37.

• Park KS, Liang MC, Raiser DM, Zamponi R, Roach RR, Curtis SJ, Walton Z, Schaffer BE, Roake CM, Zmoos AF, Kriegel C, Wong KK, Sage J*, Kim CF*. Characterization of the cell of origin for small cell lung cancer. Cell Cycle. 2011; 10(16) 2806–15. *Co-corresponding authors

• Zacharek SJ, Fillmore CF*,Lau AN*, Gludish DW*, Chou A, Ho JWK, Zamponi R, Gazit R, Bock C, Jager N, Smith ZD, Kim T, Saunders AH, Wong J, Lee JH, Roach RR, Rossi DJ, Meissner A, Gimelbrant AA, Park PJ, Kim CF. Lung stem cell self-renewal relies on Bmi1-dependent control of expression at imprinted loci. Cell Stem Cell. 2011; 9(3): 272-281.

• Curtis SJ, Sinkevicius KW, Li D, Lau AN, Roach RR, Zamponi R, Woolfenden AE, Kirsh DG, Wong KK, Kim CF. Primary tumor genotype is an important determinant in identification of lung cancer propagating cells. Cell Stem Cell, 2010; 7: 127-133.

• 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.

• Dovey J, Zacharek S, Kim CF*, Lees JA*. . Bmi1 is critical for lung tumorigenesis and bronchioalveolar stem cell expansion. Proceedings of the National Academy of Sciences of the USA. 2008. 105:11857-11862. PMCID: PMC2575250 *co-corresponding authors

• Raiser DM, Zacharek SJ, Roach RR, Curtis SJ, Sinkevicius KW, Gludish DW, Kim CF. Stem cell biology in the lung and lung cancers: employing pulmonary context and classic approaches. Cold Spring Harb Symp Quant Biol 2008. 73: 479-490.

• 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.