BBS Faculty Member - Carla Kim

Carla Kim

Children's Hospital Stem Cell Program
Department of Genetics, Harvard Medical School

Boston Children's Hospital
Karp Building, Room 8-216
300 Longwood Ave
Boston, MA 02115
Tel: 617-919-4644
Fax: 617-730-0222
Email: carla.kim@childrens.harvard.edu
Lab Members: 7 postdoctoral fellows, 1 clinical fellow, 3 technicians
Visit my lab page here.



The broad interest of the Kim Lab is to characterize the biology of stem cells in normal lung and lung cancer. Numerous lung diseases including cystic fibrosis, asthma, cancer, and emphysema involve injured or depleted bronchiolar or alveolar epithelium. 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. The Kim Lab uses cell biology, genetics, biochemistry and gene expression studies, focusing on the mouse and expanding to the human lung.

Much of the lab’s work is focused on bronchioalveolar stem cells (BASCs), a lung epithelial stem cell population that contributes to airway and alveolar cell injury repair and tumorigenesis. The lab created an orthotopic transplantation assay for lung tumor-propagating cells (TPCs), the cells that have capacity to recapitulate the tumor. This work identified the first
bona fide lung TPCs from the two most common types of lung cancer in patients and provides new opportunities to study targets for lung cancer therapy. Most recently the Kim Lab created three-dimensional co-culture and co-transplantation organoid systems that demonstrate the potential of BASCs. They can visualize the formation of airway- and alveolar-like structures from single BASCs, and they now have a way to precisely define how lung stem cell differentiation is controlled at the molecular level. Using these organoids, they showed that lung epithelial stem cells and lung endothelial cells interact in a novel BMP4-NFATc1-TSP1 signaling axis that drives lineage-specific differentiation. With unique tools in hand, the Kim Lab is working to understand how a multipotent stem cell is instructed to undergo lineage-specific differentiation in response to lung injury to achieve tissue repair. This is just a sample of the type of questions the Kim Lab is poised to answer to make transformative findings in lung stem cell biology and lung disease.



Last Update: 8/10/2015



Publications

For a complete listing of publications click here.

 


 

Fillmore CM, Xu C, Desai PT, Berry JM, Rowbotham SP, Lin YJ, Zhang H, Marquez VE, Hammerman PS, Wong KK, Kim CF. EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumors to TopoII inhibitors. Nature. 2015;520(7546):239-42.

Lee JH, Bhang DH, Beede A, Huang TL, Stripp BR, Bloch KD, Wagers AJ, Tseng YH, Ryeom S, Kim, CF. Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-Thrombospondin-1 axis. Cell. 2014; 156(3):440-455.

Lau AN, Curtis SJ, Fillmore CM, Rowbotham SP, Mohseni M, Wagner DE, Beede AM, Montoro DT, Sinkevicius KW, Walton ZE, Barrios J, Weiss DJ, Camargo FD, Wong KK, Kim CF. Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis. EMBO J. 2014; 33(5):468-481.

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.



© 2015 by the President and Fellows of Harvard College