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Related Research Units

Dana Farber Boston Childrens Cancer and Blood Disorders Center Research
Hematology and Oncology Research

Research Overview

Dr. Carla F. Kim's laboratory has pioneered the use of stem cell biology approaches for the study of adult lung progenitor cells and lung cancer. Her work has contributed to a better understanding of stem cell biology in the lung, development of innovative approaches for examining the cellular and molecular basis of cancer and pulmonary disease, and identification of new therapeutic avenues for lung cancer.

The success that Dr. Kim’s lab has had investigating the molecular pathways that regulate lung stem cells and the role of stem cells in lung cancer is a testament to her potential to make new strides in understanding lung disease and basic biology. Working with genetically engineered mouse models that accurately represent human lung cancer, Dr. Kim’s group was the first to identify cancer stem cell populations in the two most frequent types of lung cancer in patients (Cell Stem Cell, 2010 and Cancer Cell, 2014). Her lab’s knowledge in lung stem cells has revealed a new combination therapy approach for particular subsets of lung cancer patients (Fillmore et al, Nature, 2015). Dr. Kim’s lab has developed a 3D lung organoid system that makes it possible to derive specialized lung cells from lung stem cells (Lee et al, Cell, 2014).

The organoid culture system developed by the Kim Lab grows tiny replicas of lungs, allowing them to model the complex interactions of lung stem cells and their neighboring cells. Most recently, the Kim Lab used the organoid cultures to define new types of mesenchymal cells that are required to support lung injury repair (Lee et al, Cell, 2017). This system can now be used to probe the role of lung stem cells and the diverse cell types with which they interact in lung cancer, in lung diseases such as cystic fibrosis and pulmonary fibrosis, and during lung development. These advances by the Kim Lab provide a whole new way to study lung diseases in the laboratory dish and to find new therapeutic interventions.

Research Background

Dr. Carla F. Kim is an internationally renowned leader in the field of lung stem cell biology. Dr. Kim’s current research builds on her early discoveries to lead the field toward a better understanding of stem cell biology in the lung, development of innovative approaches for examining the cellular and molecular basis of lung disease and cancer, and identification of new therapeutic avenues for pulmonary diseases and lung cancer.

The impact of Dr. Kim’s work has been acknowledged in a myriad of ways. From her publication in Cell Stem Cell winning Best Cancer Paper of 2010 to her receipt of the William Rippe Distinguished Award in Lung Cancer Research from the Lung Cancer Research Foundation, she has been widely acknowledged as one of the brightest researchers in lung stem cells. Dr. Kim received her PhD in Genetics from the University of Wisconsin—Madison in 2002 and performed postdoctoral research at the MIT Center for Cancer Research. She joined the Stem Cell Program at Boston Children’s Hospital and established her laboratory in September 2006. In 2019, she was honored with the Bravo! Way to Shine award from Boston Children’s Hospital.

Publications

  1. Human Airway and Alveolar Organoids from BAL Fluid. Am J Respir Crit Care Med. 2024 06 15; 209(12):1501-1504. View Abstract
  2. Early-stage lung cancer is driven by a transitional cell state dependent on a KRAS-ITGA3-SRC axis. EMBO J. 2024 Jul; 43(14):2843-2861. View Abstract
  3. Airway injury induces alveolar epithelial and mesenchymal responses mediated by macrophages. bioRxiv. 2024 May 02. View Abstract
  4. Age-associated H3K9me2 loss alters the regenerative equilibrium between murine lung alveolar and bronchiolar progenitors. Dev Cell. 2023 Dec 18; 58(24):2974-2991.e6. View Abstract
  5. PR1P, a VEGF-stabilizing peptide, reduces injury and inflammation in acute lung injury and ulcerative colitis animal models. Front Immunol. 2023; 14:1168676. View Abstract
  6. Organoid modeling reveals the tumorigenic potential of the alveolar progenitor cell state. Res Sq. 2023 Mar 14. View Abstract
  7. Lung Cancer Stem Cells and Their Clinical Implications. Cold Spring Harb Perspect Med. 2022 05 17; 12(4). View Abstract
  8. Progenitor potential of lung epithelial organoid cells in a transplantation model. Cell Rep. 2022 04 12; 39(2):110662. View Abstract
  9. Comparison of Transplantation of Lung Organoid Cell Types: One Size Does Not Fit All. Am J Respir Cell Mol Biol. 2022 03; 66(3):340-343. View Abstract
  10. Smarca4 Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung. Cancer Discov. 2022 02; 12(2):562-585. View Abstract
  11. The aging lung: Physiology, disease, and immunity. Cell. 2021 04 15; 184(8):1990-2019. View Abstract
  12. Organoids Model Transcriptional Hallmarks of Oncogenic KRAS Activation in Lung Epithelial Progenitor Cells. Cell Stem Cell. 2020 10 01; 27(4):663-678.e8. View Abstract
  13. BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency. Cancer Res. 2020 09 15; 80(18):3841-3854. View Abstract
  14. May the (Mechanical) Force Be with AT2. Cell. 2020 01 09; 180(1):20-22. View Abstract
  15. Mesenchymal Stem Cells Increase Alveolar Differentiation in Lung Progenitor Organoid Cultures. Sci Rep. 2019 04 23; 9(1):6479. View Abstract
  16. An airway organoid is forever. EMBO J. 2019 02 15; 38(4). View Abstract
  17. Author Correction: EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors. Nature. 2018 11; 563(7732):E27. View Abstract
  18. E-Cadherin Loss Accelerates Tumor Progression and Metastasis in a Mouse Model of Lung Adenocarcinoma. Am J Respir Cell Mol Biol. 2018 08; 59(2):237-245. View Abstract
  19. Human amnion cells reverse acute and chronic pulmonary damage in experimental neonatal lung injury. Stem Cell Res Ther. 2017 Nov 10; 8(1):257. View Abstract
  20. Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6. Cell. 2017 Sep 07; 170(6):1149-1163.e12. View Abstract
  21. Intersections of lung progenitor cells, lung disease and lung cancer. Eur Respir Rev. 2017 Jun 30; 26(144). View Abstract
  22. Erratum: Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2. Nat Commun. 2017 06 09; 8:15901. View Abstract
  23. Don't Stop Re-healin'! Cancer as an Ongoing Stem Cell Affair. Cell. 2017 05 04; 169(4):563-565. View Abstract
  24. Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2. Nat Commun. 2017 04 07; 8:14922. View Abstract
  25. Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer. Cancer Discov. 2016 09; 6(9):1006-21. View Abstract
  26. Tracing the potential of lung progenitors. Nat Biotechnol. 2015 Feb; 33(2):152-4. View Abstract
  27. EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors. Nature. 2015 Apr 09; 520(7546):239-42. View Abstract
  28. Developmental biology. Mesenchymal progenitor panoply. Science. 2014 Nov 14; 346(6211):810-1. View Abstract
  29. Bone marrow-derived multipotent stromal cells attenuate inflammation in obliterative airway disease in mouse tracheal allografts. Stem Cells Int. 2014; 2014:468927. View Abstract
  30. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 2014 Aug; 14(8):535-46. View Abstract
  31. Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis. EMBO J. 2014 Jul 1; 33(13):1502. View Abstract
  32. Neurotrophin receptor TrkB promotes lung adenocarcinoma metastasis. Proc Natl Acad Sci U S A. 2014 Jul 15; 111(28):10299-304. View Abstract
  33. Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression. Cancer Cell. 2014 May 12; 25(5):590-604. View Abstract
  34. Diverse cells at the origin of lung adenocarcinoma. Proc Natl Acad Sci U S A. 2014 Apr 01; 111(13):4745-6. View Abstract
  35. Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis. EMBO J. 2014 Mar 03; 33(5):468-81. View Abstract
  36. Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell. 2014 Jan 30; 156(3):440-55. View Abstract
  37. Lung stem and progenitor cells in tissue homeostasis and disease. Curr Top Dev Biol. 2014; 107:207-233. View Abstract
  38. Very small embryonic-like stem cells from the murine bone marrow differentiate into epithelial cells of the lung. Stem Cells. 2013 Dec; 31(12):2759-66. View Abstract
  39. Thrombospondin-1 mediates oncogenic Ras-induced senescence in premalignant lung tumors. J Clin Invest. 2013 Oct; 123(10):4375-89. View Abstract
  40. Surfactant protein-C chromatin-bound green fluorescence protein reporter mice reveal heterogeneity of surfactant protein C-expressing lung cells. Am J Respir Cell Mol Biol. 2013 Mar; 48(3):288-98. View Abstract
  41. Airway epithelial progenitors are region specific and show differential responses to bleomycin-induced lung injury. Stem Cells. 2012 Sep; 30(9):1948-60. View Abstract
  42. The bed and the bugs: interactions between the tumor microenvironment and cancer stem cells. Semin Cancer Biol. 2012 Oct; 22(5-6):462-70. View Abstract
  43. Stem cells and regenerative medicine in lung biology and diseases. Mol Ther. 2012 Jun; 20(6):1116-30. View Abstract
  44. Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. Mol Cell. 2012 Feb 10; 45(3):330-43. View Abstract
  45. Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2012 May 01; 302(9):L829-37. View Abstract
  46. Isolation and characterization of distal lung progenitor cells. Methods Mol Biol. 2012; 879:109-22. View Abstract
  47. Lung stem cell self-renewal relies on BMI1-dependent control of expression at imprinted loci. Cell Stem Cell. 2011 Sep 02; 9(3):272-81. View Abstract
  48. Characterization of the cell of origin for small cell lung cancer. Cell Cycle. 2011 Aug 15; 10(16):2806-15. View Abstract
  49. Primary tumor genotype is an important determinant in identification of lung cancer propagating cells. Cell Stem Cell. 2010 Jul 02; 7(1):127-33. View Abstract
  50. p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. Science. 2010 Jan 29; 327(5965):593-6. View Abstract
  51. Separating stem cells by flow cytometry: reducing variability for solid tissues. Cell Stem Cell. 2009 Dec 04; 5(6):579-83. View Abstract
  52. Matrix modulation of compensatory lung regrowth and progenitor cell proliferation in mice. Am J Physiol Lung Cell Mol Physiol. 2010 Feb; 298(2):L158-68. View Abstract
  53. Commentary: Sca-1 and Cells of the Lung: A matter of Different Sorts. Stem Cells. 2009 Mar; 27(3):606-11. View Abstract
  54. Stem cell biology in the lung and lung cancers: using pulmonary context and classic approaches. Cold Spring Harb Symp Quant Biol. 2008; 73:479-90. View Abstract
  55. Bmi1 is critical for lung tumorigenesis and bronchioalveolar stem cell expansion. Proc Natl Acad Sci U S A. 2008 Aug 19; 105(33):11857-62. View Abstract
  56. Cellular kinetics and modeling of bronchioalveolar stem cell response during lung regeneration. Am J Physiol Lung Cell Mol Physiol. 2008 Jun; 294(6):L1158-65. View Abstract
  57. The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev. 2005 Dec 15; 19(24):3043-54. View Abstract
  58. Use of gene expression profiling to direct in vivo molecular imaging of lung cancer. Proc Natl Acad Sci U S A. 2005 Oct 04; 102(40):14404-9. View Abstract
  59. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005 Jun 17; 121(6):823-35. View Abstract

Contact Carla Kim

Phone: 617-919-4865
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