Carla F. Kim, PhD

Boston Children's Hospital

Boston Children's Hospital


carla.kim@childrens.harvard.edu

Carla F. Kim, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Associate Professor, Genetics, Harvard Medical School
  • Associate Professor, Pediatrics, Harvard Medical School
  • Assistant Professor, Medicine, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The broad interest of our lab is to characterize the biology of stem cells in normal lung and lung cancer.

We developed a method to isolate 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. We will use a combination of mouse genetics, cell biology and genomics approaches to elucidate the biology of these cells during homeostasis and tumorigenesis. An understanding of stem cell functions and regulation in normal lung will be important for innovative approaches to examine the cellular and molecular basis of cancer and diseases that effect lung epithelia as well as serving to identify potential means of early detection and therapy.

Publications

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  • 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; 520:239-42. PubMed
  • Mahoney JE, Kim CF. Tracing the potential of lung progenitors. Nat Biotechnol 2015; 33:152-4. PubMed
  • 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; 25:590-604. PubMed
  • Rowbotham SP, Kim CF. Diverse cells at the origin of lung adenocarcinoma. Proc Natl Acad Sci U S A 2014; 111:4745-6. PubMed
  • 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; 33:468-81. PubMed
  • 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; 156:440-55. PubMed
  • Mohseni M, Sun J, Lau A, Curtis S, Goldsmith J, Fox VL, Wei C, Frazier M, Samson O, Wong KK, Wong KK, Kim C, Camargo FD. A genetic screen identifies an LKB1-MARK signalling axis controlling the Hippo-YAP pathway. Nat Cell Biol 2013; 16:108-17. PubMed
  • Leeman KT, Fillmore CM, Kim CF. Lung stem and progenitor cells in tissue homeostasis and disease. Curr Top Dev Biol 2014; 107:207-33. PubMed
  • 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; 123:4375-89. PubMed
  • Mingueneau M, Kreslavsky T, Gray D, Heng T, Cruse R, Ericson J, Bendall S, Spitzer M, Nolan G, Kobayashi K, von Boehmer H, Mathis D, Benoist C, , Best AJ, Knell J, Goldrath A, Jojic V, Koller D, Shay T, Regev A, Cohen N, Brennan P, Brenner M, Kim F, Rao TN, Wagers A, Heng T, Ericson J, Rothamel K, Ortiz-Lopez A, Mathis D, Benoist C, Bezman NA, Sun JC, Min-Oo G, Kim CC, Lanier LL, Miller J, Brown B, Merad M, Gautier EL, Jakubzick C, Randolph GJ, Monach P, Blair DA, Dustin ML, Shinton SA, Hardy RR, Laidlaw D, Collins J, Gazit R, Rossi DJ, Malhotra N, Sylvia K, Kang J, Kreslavsky T, Fletcher A, Elpek K, Bellemare-Pelletier A, Malhotra D, Turley S. The transcriptional landscape of 留硫 T cell differentiation. Nat Immunol 2013. PubMed
  • Jojic V, Shay T, Sylvia K, Zuk O, Sun X, Kang J, Regev A, Koller D, , Best AJ, Knell J, Goldrath A, Jojic V, Koller D, Shay T, Regev A, Cohen N, Brennan P, Brenner M, Kim F, Rao TN, Wagers A, Heng T, Ericson J, Rothamel K, Ortiz-Lopez A, Mathis D, Benoist C, Bezman NA, Sun JC, Min-Oo G, Kim CC, Lanier LL, Miller J, Brown B, Merad M, Gautier EL, Jakubzick C, Randolph GJ, Monach P, Blair DA, Dustin ML, Shinton SA, Hardy RR, Laidlaw D, Collins J, Gazit R, Rossi DJ, Malhotra N, Sylvia K, Kang J, Kreslavsky T, Fletcher A, Elpek K, Bellemare-Pelletier A, Malhotra D, Turley S. Identification of transcriptional regulators in the mouse immune system. Nat Immunol 2013. PubMed
  • 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; 48:288-98. PubMed
  • 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; 22:462-70. PubMed
  • Lau AN, Goodwin M, Kim CF, Weiss DJ. Stem Cells and Regenerative Medicine in Lung Biology and Diseases. Mol Ther 2012. PubMed
  • Tropea KA, Leder E, Aslam M, Lau AN, Raiser DM, Lee JH, Balasubramaniam V, Fredenburgh LE, Mitsialis SA, 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. PubMed
  • 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; 45:330-43. PubMed
  • 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; 9:272-81. PubMed
  • 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; 10:2806-15. PubMed
  • 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; 7:127-33. PubMed
  • Carretero J, Shimamura T, Rikova K, Jackson AL, Wilkerson MD, Borgman CL, Buttarazzi MS, Sanofsky BA, McNamara KL, Brandstetter KA, Walton ZE, Gu TL, Silva JC, Crosby K, Shapiro GI, Maira SM, Ji H, Castrillon DH, Kim CF, García-Echeverría C, Bardeesy N, Sharpless NE, Hayes ND, Kim WY, Engelman JA, Wong KK. Integrative genomic and proteomic analyses identify targets for Lkb1-deficient metastatic lung tumors. Cancer Cell 2010; 17:547-59. PubMed
  • 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; 327:593-6. PubMed
  • 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; 5:579-83. PubMed
  • Raiser DM,Kim CF. Commentary: Sca-1 and Cells of the Lung: A matter of Different Sorts. Stem Cells 2009; 27:606-11. PubMed
  • 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; 105:11857-62. PubMed
  • Kim CF,Dirks PB. Cancer and stem cell biology: how tightly intertwined? Cell Stem Cell 2008; 3:147-50. PubMed
  • Nolen-Walston RD, Kim CF, Mazan MR, Ingenito EP, Gruntman AM, Tsai L, Boston RC, 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; 294:L1158-65. PubMed
  • Bae JH, Lee SJ, Kim CJ, Hur SY, Park YG, Lee WC, Kim YT, Ng TL, Bock HL, Park JS. Human Papillomavirus (HPV) Type Distribution in Korean Women: A Meta-Analysis. J Microbiol Biotechnol 2008; 18:788-94. PubMed
  • Perera SA, Maser RS, Xia H, McNamara K, Protopopov A, Chen L, Hezel AF, Kim CF, Bronson RT, Castrillon DH, Chin L, Bardeesy N, Depinho RA, Wong KK. Telomere dysfunction promotes genome instability and metastatic potential in a K-ras p53 mouse model of lung cancer. Carcinogenesis 2008; 29:747-53. PubMed
  • Yang Y,Iwanaga K,Raso MG,Wislez M,Hanna AE,Wieder ED,Molldrem JJ,Wistuba II,Powis G,Demayo FJ,Kim CF,Kurie JM. Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer. PLoS ONE 2008; 3:e2220. PubMed
  • 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; 293:L1092-8. PubMed
  • Sicinski P, Zacharek S, Kim C. Duality of p27Kip1 function in tumorigenesis. Genes Dev 2007; 21:1703-6. PubMed
  • Kim CB. MAPK-ing out the pathways in lung stem cell regulation. Cell Stem Cell 2008; 1:11-3. PubMed
  • 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; 102:14404-9. PubMed
  • 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; 121:823-35. PubMed
  • Kim CF, Jackson EL, Kirsch DG, Grimm J, Shaw AT, Lane K, Kissil J, Olive KP, Sweet-Cordero A, Weissleder R, Jacks T. Mouse models of human non-small-cell lung cancer: raising the bar. Cold Spring Harb Symp Quant Biol 2006; 70:241-50. PubMed
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