Information

Related Research Units

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

Research Overview

The Camargo laboratory focuses on the study of adult stem cell biology, organ size regulation, and cancer.

Organ size regulation:

Despite fantastic progress in developmental biology research over the past decade, one aspect of development and tissue homeostasis for which very little is understood is how individual tissues reach and then maintain their appropriate size. Classic studies have demonstrated that tissues are able to "sense" their size and expand or shrink until a correct dimension has been reached. Nevertheless, the nature of the molecules and pathways involved in this process remains mysterious. The Camargo laboratory utilizes a variety of genetic, biochemical, and high throughput technologies to identify molecules and mechanisms that regulate this fascinating process in mammals.

The Camargo lab is particularly interested in studying the function of an emerging highly conserved developmental signaling cascade, the Hippo pathway, and its effects on tissue size, homeostasis and cancer. Their previous work has demonstrated that Hippo signaling can be a very potent regulator of organ size in mice and has also provided a conceptual link between organ size regulation and stem cell activity through Hippo signals. These studies are now aimed at fully dissecting the components and the role of this cascade in somatic stem cells. For instance, the Camargo lab is currently performing genome-wide gain- and loss-of-function genetic screens to identify new regulators of Hippo signaling in mammals. Additionally, they have generated several animal models with mutations that can conditionally activate or deactivate Hippo signaling in our tissue of interest. These models will allow the Camargo lab the opportunity to gain an understanding of the plethora of roles Hippo signaling plays during development, tissue regeneration, and malignancy. Insight into these processes will shed light on fundamental aspects of tissue regeneration and facilitate the development of therapeutic approaches based on cellular transplantation.

Characterization of hematopoietic stem cells in vivo:

The Camargo laboratory also has a strong interest in studying the cellular and molecular biology of hematopoietic stem cells. Our studies focus primarily on the in vivo roles of transcription factors and microRNAs in stem cell fate decisions, differentiation, and malignancy. Additionally, we have recently developed a novel methodology for the tracking and monitoring of individual hematopoietic stem cells and their progeny, which they think will evolve into an entirely novel experimental paradigm to study complex populations of stem cells in situ. This model will be an invaluable resource in the years to come to understand the behavior, dynamics and heterogeneity of stem cells in an array of disease conditions.

Research Background

Dr. Camargo joined Children's Hospital and the Stem Cell and Regenerative Biology Department at Harvard University in 2009. Dr. Camargo was named a 2009 V Foundation Scholar and is the recipient of the NIH Director’s New Innovator Award. Most recently, he has received the Vilcek Prize for Creative Promise in Biomedical Science and the ISSCR’s Dr. Susan Lim Award for Outstanding Young Investigator.

In February 2022, Dr. Camargo was named the first Regenerative Biology Endowed Chair, in recognition of his scientific contributions and strong leadership.

Contact:

Aubrey Plumb, Administrative Assistant
617-919-2015
aubrey.plumb@childrens.harvard.edu

 

Publications

  1. CARLIN: A Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression. Methods Mol Biol. 2025; 2886:281-298. View Abstract
  2. A mouse model with high clonal barcode diversity for joint lineage, transcriptomic, and epigenomic profiling in single cells. Cell. 2023 11 09; 186(23):5183-5199.e22. View Abstract
  3. Stiffness Restricts the Stemness of the Intestinal Stem Cells and Skews Their Differentiation Toward Goblet Cells. Gastroenterology. 2023 06; 164(7):1137-1151.e15. View Abstract
  4. Taz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity. Nat Commun. 2022 09 03; 13(1):5187. View Abstract
  5. Lifelong multilineage contribution by embryonic-born blood progenitors. Nature. 2022 06; 606(7915):747-753. View Abstract
  6. Publisher Correction: Quantification of bone marrow interstitial pH and calcium concentration by intravital ratiometric imaging. Nat Commun. 2022 Mar 17; 13(1):1563. View Abstract
  7. Hippo signalling in the liver: role in development, regeneration and disease. Nat Rev Gastroenterol Hepatol. 2022 05; 19(5):297-312. View Abstract
  8. Quantification of bone marrow interstitial pH and calcium concentration by intravital ratiometric imaging. Nat Commun. 2022 01 19; 13(1):393. View Abstract
  9. External signals regulate continuous transcriptional states in hematopoietic stem cells. Elife. 2021 12 23; 10. View Abstract
  10. YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis. EMBO Mol Med. 2021 12 07; 13(12):e14351. View Abstract
  11. Mouse multipotent progenitor 5 cells are located at the interphase between hematopoietic stem and progenitor cells. Blood. 2021 06 10; 137(23):3218-3224. View Abstract
  12. YAP-dependent proliferation by a small molecule targeting annexin A2. Nat Chem Biol. 2021 07; 17(7):767-775. View Abstract
  13. Reconstructing the Lineage Histories and Differentiation Trajectories of Individual Cancer Cells in Myeloproliferative Neoplasms. Cell Stem Cell. 2021 03 04; 28(3):514-523.e9. View Abstract
  14. Systems analysis of hematopoiesis using single-cell lineage tracing. Curr Opin Hematol. 2021 01; 28(1):18-27. View Abstract
  15. Adult blood stem cell localization reflects the abundance of reported bone marrow niche cell types and their combinations. Blood. 2020 11 12; 136(20):2296-2307. View Abstract
  16. Regenerative Reprogramming of the Intestinal Stem Cell State via Hippo Signaling Suppresses Metastatic Colorectal Cancer. Cell Stem Cell. 2020 10 01; 27(4):590-604.e9. View Abstract
  17. Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis. Nature. 2020 07; 583(7817):585-589. View Abstract
  18. An Engineered CRISPR-Cas9 Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression Profiles in Single Cells. Cell. 2020 Jun 25; 181(7):1693-1694. View Abstract
  19. An Engineered CRISPR-Cas9 Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression Profiles in Single Cells. Cell. 2020 06 11; 181(6):1410-1422.e27. View Abstract
  20. Lats1/2 Sustain Intestinal Stem Cells and Wnt Activation through TEAD-Dependent and Independent Transcription. Cell Stem Cell. 2020 05 07; 26(5):675-692.e8. View Abstract
  21. Live-animal imaging of native haematopoietic stem and progenitor cells. Nature. 2020 02; 578(7794):278-283. View Abstract
  22. Reconstructed Single-Cell Fate Trajectories Define Lineage Plasticity Windows during Differentiation of Human PSC-Derived Distal Lung Progenitors. Cell Stem Cell. 2020 04 02; 26(4):593-608.e8. View Abstract
  23. Lineage tracing on transcriptional landscapes links state to fate during differentiation. Science. 2020 02 14; 367(6479). View Abstract
  24. Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway. Cancer Cell. 2020 01 13; 37(1):104-122.e12. View Abstract
  25. Hepatocyte Stress Increases Expression of Yes-Associated Protein and Transcriptional Coactivator With PDZ-Binding Motif in Hepatocytes to Promote Parenchymal Inflammation and Fibrosis. Hepatology. 2020 05; 71(5):1813-1830. View Abstract
  26. Single-Cell Analysis of the Liver Epithelium Reveals Dynamic Heterogeneity and an Essential Role for YAP in Homeostasis and Regeneration. Cell Stem Cell. 2019 07 03; 25(1):23-38.e8. View Abstract
  27. Somatic Mutations Reveal Lineage Relationships and Age-Related Mutagenesis in Human Hematopoiesis. Cell Rep. 2018 11 27; 25(9):2308-2316.e4. View Abstract
  28. NUAK2 is a critical YAP target in liver cancer. Nat Commun. 2018 11 16; 9(1):4834. View Abstract
  29. Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer. Cell Rep. 2018 10 30; 25(5):1304-1317.e5. View Abstract
  30. Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth. EMBO J. 2018 11 15; 37(22). View Abstract
  31. YAP-TEAD signaling promotes basal cell carcinoma development via a c-JUN/AP1 axis. EMBO J. 2018 09 03; 37(17). View Abstract
  32. Clonal analysis of lineage fate in native haematopoiesis. Nature. 2018 01 11; 553(7687):212-216. View Abstract
  33. YAP suppresses gluconeogenic gene expression through PGC1a. Hepatology. 2017 12; 66(6):2029-2041. View Abstract
  34. HUWE1 is a critical colonic tumour suppressor gene that prevents MYC signalling, DNA damage accumulation and tumour initiation. EMBO Mol Med. 2017 02; 9(2):181-197. View Abstract
  35. Hippo Signaling in the Liver Regulates Organ Size, Cell Fate, and Carcinogenesis. Gastroenterology. 2017 02; 152(3):533-545. View Abstract
  36. Conversion of Terminally Committed Hepatocytes to Culturable Bipotent Progenitor Cells with Regenerative Capacity. Cell Stem Cell. 2017 01 05; 20(1):41-55. View Abstract
  37. Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth. Nat Cell Biol. 2016 08; 18(8):886-896. View Abstract
  38. YAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic Enhancers. Mol Cell. 2015 Oct 15; 60(2):328-37. View Abstract
  39. Emerging evidence on the role of the Hippo/YAP pathway in liver physiology and cancer. J Hepatol. 2015 Dec; 63(6):1491-501. View Abstract
  40. MicroRNA-223 dose levels fine tune proliferation and differentiation in human cord blood progenitors and acute myeloid leukemia. Exp Hematol. 2015 Oct; 43(10):858-868.e7. View Abstract
  41. Clonal dynamics of native haematopoiesis. Nature. 2014 Oct 16; 514(7522):322-7. View Abstract
  42. Cytokinesis failure triggers hippo tumor suppressor pathway activation. Cell. 2014 Aug 14; 158(4):833-848. View Abstract
  43. The Hippo transducer YAP1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation. Cancer Cell. 2014 Aug 11; 26(2):273-87. View Abstract
  44. Yap tunes airway epithelial size and architecture by regulating the identity, maintenance, and self-renewal of stem cells. Dev Cell. 2014 Jul 28; 30(2):151-65. View Abstract
  45. Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis. EMBO J. 2014 Jul 1; 33(13):1502. View Abstract
  46. Hippo pathway activity influences liver cell fate. Cell. 2014 Jun 05; 157(6):1324-1338. View Abstract
  47. Dynamic alterations in Hippo signaling pathway and YAP activation during liver regeneration. Am J Physiol Gastrointest Liver Physiol. 2014 Jul 15; 307(2):G196-204. View Abstract
  48. Yap1 is required for endothelial to mesenchymal transition of the atrioventricular cushion. J Biol Chem. 2014 Jul 04; 289(27):18681-92. View Abstract
  49. Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer. Cell. 2014 Feb 27; 156(5):893-906. View Abstract
  50. 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
  51. A genetic screen identifies an LKB1-MARK signalling axis controlling the Hippo-YAP pathway. Nat Cell Biol. 2014 Jan; 16(1):108-17. View Abstract
  52. Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia. Blood. 2013 Oct 17; 122(16):2888-92. View Abstract
  53. The hippo tumor suppressor network: from organ size control to stem cells and cancer. Cancer Res. 2013 Nov 01; 73(21):6389-92. View Abstract
  54. The Ets transcription factor GABP is a component of the hippo pathway essential for growth and antioxidant defense. Cell Rep. 2013 May 30; 3(5):1663-77. View Abstract
  55. The Hippo superhighway: signaling crossroads converging on the Hippo/Yap pathway in stem cells and development. Curr Opin Cell Biol. 2013 Apr; 25(2):247-53. View Abstract
  56. YAP mediates crosstalk between the Hippo and PI(3)K–TOR pathways by suppressing PTEN via miR-29. Nat Cell Biol. 2012 Dec; 14(12):1322-9. View Abstract
  57. Restriction of intestinal stem cell expansion and the regenerative response by YAP. Nature. 2013 Jan 03; 493(7430):106-10. View Abstract
  58. The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells. J Cell Sci. 2012 Dec 15; 125(Pt 24):6009-19. View Abstract
  59. Hippo signaling in mammalian stem cells. Semin Cell Dev Biol. 2012 Sep; 23(7):818-26. View Abstract
  60. The Hippo signaling pathway and stem cell biology. Trends Cell Biol. 2012 Jul; 22(7):339-46. View Abstract
  61. YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. Proc Natl Acad Sci U S A. 2012 Feb 14; 109(7):2394-9. View Abstract
  62. Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci U S A. 2011 Dec 06; 108(49):E1312-20. View Abstract
  63. PR-domain-containing Mds1-Evi1 is critical for long-term hematopoietic stem cell function. Blood. 2011 Oct 06; 118(14):3853-61. View Abstract
  64. Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells. Blood. 2011 Sep 22; 118(12):3350-8. View Abstract
  65. a-catenin is a tumor suppressor that controls cell accumulation by regulating the localization and activity of the transcriptional coactivator Yap1. Sci Signal. 2011 May 24; 4(174):ra33. View Abstract
  66. Yap1 acts downstream of a-catenin to control epidermal proliferation. Cell. 2011 Mar 04; 144(5):782-95. View Abstract
  67. Generation of iPSCs from cultured human malignant cells. Blood. 2010 May 20; 115(20):4039-42. View Abstract
  68. Regulation of lymphoid versus myeloid fate 'choice' by the transcription factor Mef2c. Nat Immunol. 2009 Mar; 10(3):289-96. View Abstract
  69. The impact of microRNAs on protein output. Nature. 2008 Sep 04; 455(7209):64-71. View Abstract
  70. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature. 2008 Feb 28; 451(7182):1125-9. View Abstract
  71. Isolation and functional characterization of side population stem cells. Methods Mol Biol. 2008; 430:183-93. View Abstract
  72. YAP1 increases organ size and expands undifferentiated progenitor cells. Curr Biol. 2007 Dec 04; 17(23):2054-60. View Abstract
  73. Oct4 expression is not required for mouse somatic stem cell self-renewal. Cell Stem Cell. 2007 Oct 11; 1(4):403-15. View Abstract
  74. Hematopoietic stem cells do not engraft with absolute efficiencies. Blood. 2006 Jan 15; 107(2):501-7. View Abstract
  75. Isolation and characterization of side population cells. Methods Mol Biol. 2005; 290:343-52. View Abstract
  76. Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners. J Clin Invest. 2004 May; 113(9):1266-70. View Abstract
  77. Stem cell plasticity: from transdifferentiation to macrophage fusion. Cell Prolif. 2004 Feb; 37(1):55-65. View Abstract
  78. Primitive adult hematopoietic stem cells can function as osteoblast precursors. Proc Natl Acad Sci U S A. 2003 Dec 23; 100(26):15877-82. View Abstract
  79. Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nat Med. 2003 Dec; 9(12):1520-7. View Abstract
  80. Muscle-derived hematopoietic stem cells are hematopoietic in origin. Proc Natl Acad Sci U S A. 2002 Feb 05; 99(3):1341-6. View Abstract
  81. Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease. Life Sci. 2001 Nov 30; 70(2):131-42. View Abstract
  82. Germline incorporation of a replication-defective adenoviral vector in mice does not alter immune responses to adenoviral vectors. Mol Ther. 2000 Nov; 2(5):496-504. View Abstract
  83. Pharmacological and genetic modifications of somatic cholesterol do not substantially alter the course of CNS disease in Niemann-Pick C mice. J Inherit Metab Dis. 2000 Feb; 23(1):54-62. View Abstract

Contact Fernando Camargo

Phone: 617-919-2102
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