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Biochemistry Home »

Biochemistry Department - Primary Faculty

Barbara Bedogni, Ph.D.

Assistant Professor

Education

  • Ph.D.: Catholic University, Rome, Italy
  • Postdoc: Department of Radiation Oncology, Stanford University, Stanford, CA

Research Interests

The goal of our lab is to understand how the interaction between the tissue microenvironment and oncogenes contributes to melanoma development and progression.

Melanoma results from the interaction of altered intracellular tumor suppressors and oncogenes with the microenvironment in which these changes occur. Normal human and mouse skin is mildly hypoxic and melanocytes are localized in areas of hypoxia, suggesting that skin hypoxia might represent a permissive environment for melanocyte survival and a promoting factor that contributes to melanocyte transformation. In fact, Akt is able to transform melanocytes only when in the presence of a mild hypoxic environment normally found in skin and this is mediated by the transcription factor HIF-1α (Hypoxia Inducible Factor-1α).

The Notch signaling pathway lies at the convergence of the signaling cascade triggered by hypoxia and Akt and is required for melanocyte transformation and melanoma development. The Notch signaling pathway is an evolutionarily conserved signaling cascade that affects cell fate decisions and many differentiation processes during both embryonic and postnatal development, including proliferation, survival, EMT/MET (epithelial-mesenchymal transition/mesenchymal-epithelial transition) in both normal and tumor cells.

One of the research interests of our lab is to understand how Notch signaling contributes to melanoma development and progression. We have evidence suggesting that the Notch signaling pathway is elevated in melanoma. The goal of our research is to dissect the mechanism by which Notch1 and its effectors and other Notch receptors and ligands affect melanomagenesis. These studies will benefit from a vast array of melanoma cell lines and both melanoma orthotopic and transgenic mouse models for studies in vivo.

Our lab is also interested in understanding what role hypoxia and the Hypoxia Inducible Factors (HIF-1α and HIF-2α) play in the survival and maintenance of melanocyte precursor cells and whether they contribute to melanomagenesis. Our hypothesis is that normal tissue hypoxia creates a permissive niche for stem/precursor cells via regulation of specific genes (e.g. Oct-4) and that, by maintaining cells in a more precursor-like state may contribute to tumorigenesis. These studies will take advantage of conditional KO mice where HIF-1α and/or HIF-2α can be excised specifically in the melanocytic lineage and of transgenic melanoma mouse models for the study of melanomagenesis in vivo.

The ultimate goal of our research is to understand the genetics of melanoma in order to gain new knowledge that can lead to new therapeutic approaches.

Selected References

  • Razorenova O. V., Finger E. C., Colavitti R., Chernikova S. B., Boiko A. D., Chan C. K., Krieg A., Bedogni B., Lagory E., Weissman I. L., Broome-Powell M., and Giaccia A. J.
    “VHL loss in renal cell carcinoma leads to up-regulation of CUB domain-containing protein 1 to stimulate PKC{delta}-driven migration”
    Proc Natl Acad Sci U S A 108 (5): 1931-6 (2011). Read article in PubMedCentral
  • Bedogni B. and Powell M. B.
    “Unique transforming properties of Notch1 in human melanocytes”
    Pigment Cell Melanoma Res 22 (6): 702-3 (2009).
  • Bedogni B. and Powell M. B.
    “Hypoxia, melanocytes and melanoma - survival and tumor development in the permissive microenvironment of the skin”
    Pigment Cell Melanoma Res 22 (2): 166-74 (2009). Read article in PubMedCentral
  • Bedogni B, Warneke JA, Nickoloff BJ, Giaccia AJ, Powell MB.
    “Notch1 is a mediator of Akt and Hypoxia in melanoma development.”
    J. Clin. Invest. 118 (11): 3660-70, (2008). Read article in PubMedCentral
  • Bedogni B., Welford S. M., Kwan A. C., Ranger-Moore J., Saboda K., and Powell M. B.
    “Inhibition of phosphatidylinositol-3-kinase and mitogen-activated protein kinase kinase 1/2 prevents melanoma development and promotes melanoma regression in the transgenic TPRas mouse model”
    Mol Cancer Ther 5 (12): 3071-7 (2006).
  • Bedogni B., Welford S. M., Cassarino D. S., Nickoloff B. J., Giaccia A. J., and Powell M. B.
    “The hypoxic microenvironment of the skin contributes to Akt-mediated melanocyte transformation”
    Cancer Cell 8 (6): 443-54 (2005).
  • Bedogni B., O'Neill M. S., Welford S. M., Bouley D. M., Giaccia A. J., Denko N. C., and Powell M. B.
    “Topical treatment with inhibitors of the phosphatidylinositol 3'-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways reduces melanoma development in severe combined immunodeficient mice”
    Cancer Res 64 (7): 2552-60 (2004).

 

Barbara Bedogni Faculty's publications at pubmed