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.

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

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  1. Gupta M, Concepcion CP, Fahey CG, Keshishian H, Bhutkar A, Brainson CF, Sanchez-Rivera FJ, Pessina P, Kim JY, Simoneau A, Paschini M, Beytagh MC, Stanclift CR, Schenone M, Mani DR, Li C, Oh A, Li F, Hu H, Karatza A, Bronson RT, Shaw AT, Hata AN, Wong KK, Zou L, Carr SA, Jacks T, Kim CF. BRG1 loss predisposes lung cancers to replicative stress and ATR dependency. Cancer Res. 2020 Jul 20. View abstract
  2. Sainz de Aja J, Kim CF. May the (Mechanical) Force Be with AT2. Cell. 2020 01 09; 180(1):20-22. View abstract
  3. Leeman KT, Pessina P, Lee JH, Kim CF. Mesenchymal Stem Cells Increase Alveolar Differentiation in Lung Progenitor Organoid Cultures. Sci Rep. 2019 04 23; 9(1):6479. View abstract
  4. Paschini M, Kim CF. An airway organoid is forever. EMBO J. 2019 02 15; 38(4). View abstract
  5. Fillmore CM, Xu C, Desai PT, Berry JM, Rowbotham SP, Lin YJ, Zhang H, Marquez VE, Hammerman PS, Wong KK, Kim CF. Author Correction: EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors. Nature. 2018 11; 563(7732):E27. View abstract
  6. Sinkevicius KW, Bellaria KJ, Barrios J, Pessina P, Gupta M, Brainson CF, Bronson RT, Kim CF. 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
  7. Zhu D, Tan J, Maleken AS, Muljadi R, Chan ST, Lau SN, Elgass K, Leaw B, Mockler J, Chambers D, Leeman KT, Kim CF, Wallace EM, Lim R. 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
  8. Lee JH, Tammela T, Hofree M, Choi J, Marjanovic ND, Han S, Canner D, Wu K, Paschini M, Bhang DH, Jacks T, Regev A, Kim CF. Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6. Cell. 2017 Sep 07; 170(6):1149-1163.e12. View abstract
  9. Kim CF. Intersections of lung progenitor cells, lung disease and lung cancer. Eur Respir Rev. 2017 Jun 30; 26(144). View abstract
  10. Zhang H, Brainson CF, Koyama S, Redig AJ, Chen T, Li S, Gupta M, Garcia-de-Alba C, Paschini M, Herter-Sprie GS, Lu G, Zhang X, Marsh BP, Tuminello SJ, Xu C, Chen Z, Wang X, Akbay EA, Zheng M, Palakurthi S, Sholl LM, Rustgi AK, Kwiatkowski DJ, Alan Diehl J, Bass AJ, Sharpless NE, Dranoff G, Hammerman PS, Ji H, Bardeesy N, Saur D, Watanabe H, Kim CF, Wong KK. Erratum: Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2. Nat Commun. 2017 06 09; 8:15901. View abstract
  11. Rowbotham SP, Kim CF. Don't Stop Re-healin'! Cancer as an Ongoing Stem Cell Affair. Cell. 2017 05 04; 169(4):563-565. View abstract
  12. Zhang H, Fillmore Brainson C, Koyama S, Redig AJ, Chen T, Li S, Gupta M, Garcia-de-Alba C, Paschini M, Herter-Sprie GS, Lu G, Zhang X, Marsh BP, Tuminello SJ, Xu C, Chen Z, Wang X, Akbay EA, Zheng M, Palakurthi S, Sholl LM, Rustgi AK, Kwiatkowski DJ, Diehl JA, Bass AJ, Sharpless NE, Dranoff G, Hammerman PS, Ji H, Bardeesy N, Saur D, Watanabe H, Kim CF, Wong KK. Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2. Nat Commun. 2017 04 07; 8:14922. View abstract
  13. Zhang H, Qi J, Reyes JM, Li L, Rao PK, Li F, Lin CY, Perry JA, Lawlor MA, Federation A, De Raedt T, Li YY, Liu Y, Duarte MA, Zhang Y, Herter-Sprie GS, Kikuchi E, Carretero J, Perou CM, Reibel JB, Paulk J, Bronson RT, Watanabe H, Brainson CF, Kim CF, Hammerman PS, Brown M, Cichowski K, Long H, Bradner JE, Wong KK. Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer. Cancer Discov. 2016 09; 6(9):1006-21. View abstract
  14. Mahoney JE, Kim CF. Tracing the potential of lung progenitors. Nat Biotechnol. 2015 Feb; 33(2):152-4. View abstract
  15. 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 tumours to TopoII inhibitors. Nature. 2015 Apr 09; 520(7546):239-42. View abstract
  16. Lee JH, Kim CF. Developmental biology. Mesenchymal progenitor panoply. Science. 2014 Nov 14; 346(6211):810-1. View abstract
  17. Casey A, Dirks F, Liang OD, Harrach H, Schuette-Nuetgen K, Leeman K, Kim CF, Gerard C, Subramaniam M. Bone marrow-derived multipotent stromal cells attenuate inflammation in obliterative airway disease in mouse tracheal allografts. Stem Cells Int. 2014; 2014:468927. View abstract
  18. Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 2014 Aug; 14(8):535-46. View abstract
  19. 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 Jul 1; 33(13):1502. View abstract
  20. Sinkevicius KW, Kriegel C, Bellaria KJ, Lee J, Lau AN, Leeman KT, Zhou P, Beede AM, Fillmore CM, Caswell D, Barrios J, Wong KK, Sholl LM, Schlaeger TM, Bronson RT, Chirieac LR, Winslow MM, Haigis MC, Kim CF. Neurotrophin receptor TrkB promotes lung adenocarcinoma metastasis. Proc Natl Acad Sci U S A. 2014 Jul 15; 111(28):10299-304. View abstract
  21. Xu C, Fillmore CM, Koyama S, Wu H, Zhao Y, Chen Z, Herter-Sprie GS, Akbay EA, Tchaicha JH, Altabef A, Reibel JB, Walton Z, Ji H, Watanabe H, Jänne PA, Castrillon DH, Rustgi AK, Bass AJ, Freeman GJ, Padera RF, Dranoff G, Hammerman PS, Kim CF, Wong KK. 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
  22. Rowbotham SP, Kim CF. Diverse cells at the origin of lung adenocarcinoma. Proc Natl Acad Sci U S A. 2014 Apr 01; 111(13):4745-6. View abstract
  23. 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 Mar 03; 33(5):468-81. View abstract
  24. 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 Jan 30; 156(3):440-55. View abstract
  25. Leeman KT, Fillmore CM, Kim CF. Lung stem and progenitor cells in tissue homeostasis and disease. Curr Top Dev Biol. 2014; 107:207-233. View abstract
  26. Kassmer SH, Jin H, Zhang PX, Bruscia EM, Heydari K, Lee JH, Kim CF, Kassmer SH, Krause DS, Krouse D. 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
  27. Baek KH, Bhang D, Zaslavsky A, Wang LC, Vachani A, Kim CF, Albelda SM, Evan GI, Ryeom S. Thrombospondin-1 mediates oncogenic Ras-induced senescence in premalignant lung tumors. J Clin Invest. 2013 Oct; 123(10):4375-89. View abstract
  28. Lee JH, Kim J, Gludish D, Roach RR, Saunders AH, Barrios J, Woo AJ, Chen H, Conner DA, Fujiwara Y, Stripp BR, Kim CF. 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
  29. Chen H, Matsumoto K, Brockway BL, Rackley CR, Liang J, Lee JH, Jiang D, Noble PW, Randell SH, Kim CF, Stripp BR. 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
  30. Castaño Z, Fillmore CM, Kim CF, McAllister SS. 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
  31. Lau AN, Goodwin M, Kim CF, Weiss DJ. Stem cells and regenerative medicine in lung biology and diseases. Mol Ther. 2012 Jun; 20(6):1116-30. View abstract
  32. Tropea KA, Leder E, Aslam M, Lau AN, Raiser DM, Lee JH, Balasubramaniam V, Fredenburgh LE, Alex Mitsialis S, Kourembanas S, Kim CF. 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
  33. Yu M, Mazor T, Huang H, Huang HT, Kathrein KL, Woo AJ, Chouinard CR, Labadorf A, Akie TE, Moran TB, Xie H, Zacharek S, Taniuchi I, Roeder RG, Kim CF, Zon LI, Fraenkel E, Cantor AB. 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
  34. Driscoll B, Kikuchi A, Lau AN, Lee J, Reddy R, Jesudason E, Kim CF, Warburton D. Isolation and characterization of distal lung progenitor cells. Methods Mol Biol. 2012; 879:109-22. View abstract
  35. Zacharek SJ, Fillmore CM, Lau AN, Gludish DW, Chou A, Ho JW, Zamponi R, Gazit R, Bock C, Jäger N, Smith ZD, Kim TM, 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 Sep 02; 9(3):272-81. View abstract
  36. 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 Aug 15; 10(16):2806-15. View abstract
  37. Curtis SJ, Sinkevicius KW, Li D, Lau AN, Roach RR, Zamponi R, Woolfenden AE, Kirsch DG, Wong KK, Kim CF. 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
  38. Kirsch DG, Santiago PM, di Tomaso E, Sullivan JM, Hou WS, Dayton T, Jeffords LB, Sodha P, Mercer KL, Cohen R, Takeuchi O, Korsmeyer SJ, Bronson RT, Kim CF, Haigis KM, Jain RK, Jacks T. p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. Science. 2010 Jan 29; 327(5965):593-6. View abstract
  39. Alexander CM, Puchalski J, Klos KS, Badders N, Ailles L, Kim CF, Dirks P, Smalley MJ. Separating stem cells by flow cytometry: reducing variability for solid tissues. Cell Stem Cell. 2009 Dec 04; 5(6):579-83. View abstract
  40. Hoffman AM, Shifren A, Mazan MR, Gruntman AM, Lascola KM, Nolen-Walston RD, Kim CF, Tsai L, Pierce RA, Mecham RP, Ingenito EP. 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
  41. Raiser DM, Kim CF. Commentary: Sca-1 and Cells of the Lung: A matter of Different Sorts. Stem Cells. 2009 Mar; 27(3):606-11. View abstract
  42. Raiser DM, Zacharek SJ, Roach RR, Curtis SJ, Sinkevicius KW, Gludish DW, Kim CF. 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
  43. Dovey JS, Zacharek SJ, Kim CF, Lees JA. 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
  44. Nolen-Walston RD, Kim CF, Mazan MR, Ingenito EP, Gruntman AM, Tsai L, Boston R, Woolfenden AE, Jacks T, Hoffman AM. 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
  45. Morales M, Theunissen JW, Kim CF, Kitagawa R, Kastan MB, Petrini JH. 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
  46. Grimm J, Kirsch DG, Windsor SD, Kim CF, Santiago PM, Ntziachristos V, Jacks T, Weissleder R. 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
  47. Kim CF, 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 Jun 17; 121(6):823-35. View abstract