Stem Cell Program Labs

The Camargo Lab

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

Laboratory Website: https://camargolab.squarespace.com

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. Our laboratory utilizes a variety of genetic, biochemical, and high throughput technologies to identify molecules and mechanisms that regulate this fascinating process in mammals.

We are 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. Our 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. Our studies are now aimed at fully dissecting the components and the role of this cascade in somatic stem cells. For instance, we are currently performing genome-wide gain- and loss-of-function genetic screens to identify new regulators of Hippo signaling in mammals. Additionally, we have generated several animal models with mutations that can conditionally activate or deactivate Hippo signaling in our tissue of interest. These models will allow us 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:

Our 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 we 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.

Read more about our lab’s work in this Journal of Cell Biology interview.

 

SELECTED REFERENCES

Maglic D, Schlegelmilch K, Dost AF, Panero R, Dill MT, Calogero RA, Camargo FD. YAP-TEAD signaling promotes basal cell carcinoma development via a c-JUN/AP1 axis. EMBO J. 2018 Sep 3;37(17). pii: e98642. doi: 10.15252/embj.201798642. Epub 2018 Jul 23. PMID: 30037824

Rodriguez-Fraticelli AE, Wolock SL, Weinreb CS, Panero R, Patel SH, Jankovic M, Sun J, Calogero RA, Klein AM, Camargo FD. Clonal analysis of lineage fate in native haematopoiesis. Nature. 2018 Jan 11;553(7687):212-216. doi: 10.1038/nature25168. Epub 2018 Jan 3. PubMed PMID: 29323290; PubMed Central PMCID: PMC5884107.

Hu Y, Shin DJ, Pan H, Lin Z, Dreyfuss JM, Camargo FD, Miao J, Biddinger SB. YAP suppresses gluconeogenic gene expression through PGC1α. Hepatology. 2017 Dec;66(6):2029-2041. doi: 10.1002/hep.29373. Epub 2017 Oct 30. PubMed PMID: 28714135.

Patel SH, Camargo FD, Yimlamai D. Hippo Signaling in the Liver Regulates Organ Size, Cell Fate, and Carcinogenesis. Gastroenterology. 2017 Feb;152(3):533-545. doi: 10.1053/j.gastro.2016.10.047. Epub 2016 Dec 19. Review. PubMed PMID: 28003097; PubMed Central PMCID: PMC5285449.

Katsuda T, Kawamata M, Hagiwara K, Takahashi RU, Yamamoto Y, Camargo FD, Ochiya T. Conversion of Terminally Committed Hepatocytes to Culturable Bipotent Progenitor Cells with Regenerative Capacity. Cell Stem Cell. 2017 Jan 5;20(1):41-55. doi: 10.1016/j.stem.2016.10.007. Epub 2016 Nov 10. PubMed PMID: 27840021.

 

CAMARGO LABORATORY STAFF

Sarah Bowling – Postdoctoral Fellow

Michael Dill – Postdoctoral Fellow

Alejo Rodriguez-Fraticelli – Postdoctoral Fellow

Sophia Shalhout – Postdoctoral Fellow

Wei-Chien Yuan – Postdoctoral Fellow

 

Priscilla Cheung – Graduate Student

Sachin Patel – Graduate Student

 

Qi Yu – Lab Manager

Giving

Spotlight

  • The secret lives of stem cells

    Through a novel technique using genetic tags as “barcodes,” Fernando Camargo, PhD, of the Stem Cell Program at Children’s Hospital Boston is tracking the live workings of adult stem cells in mice, under a National Institutes of Health New Innovator Award. Camargo is monitoring the day-to-day activity and differentiation of individual stem cells and their offspring in their natural living environment over time. Although the work will track stem cells in the blood-forming system, the model is applicable to a variety of tissues and will yield many insights applicable to human disease and potential treatment by regenerating diseased or damaged tissues.