Translational oncology, Lab Dr. Olga Shakhova

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Reserach interests


The observation on striking parallels between cancer cells and stem cells might lead to fundamental changes in the future therapy against cancer. Tumors that originate from neural crest-derived cells, including melanoma, closely resemble their neural crest origin in the molecular signature, differentiation potential, and ability to migrate and invade host tissues and represent a heterogeneous group of malignancies, accounting for thousands of deaths per year worldwide. Melanoma tissue is often heterogeneous and, in addition to melanocytes, contains cells of other neural crest lineages. We have recently identified the neural crest stem cell transcription factor SOX10 as a new downstream target of oncogenic RAS pathway and demonstrated that SOX10 is instrumental for the development of giant congenital naevi and melanoma.

To gain further insight into Sox10-mediated melanoma progression, we plan to concentrate on dissecting the upstream and downstream targets of Sox10 using a combination of in vivo (mouse models of melanoma) and in vitro (human melanoma cell lines) approaches. We also aim at understanding how SOX10 might be involved in mediating resistance to RAS-BRAF-MEK-ERK pathway-targeted drugs in melanoma cells. Another interest of our laboratory is to identify the cellular origin of melanoma using in vivo genetic lineage-tracing analysis of melanoma mouse models.

Publications

1. Shakhova O, Cheng P, Mishra PJ, Zingg D, Schaefer SM, Debbache J, Häusel J, Matter C, Guo T, Davis S, Meltzer P, Mihic-Probst D, Moch H, Wegner M, Merlino G, Levesque MP, Dummer R, Santoro R, Cinelli P, Sommer L. (2015). Antagonistic cross-regulation between Sox9 and Sox10 controls an anti-tumorigenic program in melanoma. PLoS Genet. 2015 Jan 28;11(1):e1004877. doi: 10.1371/journal.pgen.1004877.

2. Shakhova O (2014). Neural crest stem cells in melanoma development. Current Opinion in Oncology. Mar;26(2):215-21.

3. Harris ML, Buac K, Shakhova O, Haami R, Wegner M, Sommer L, Pavan W. (2013). A dual role for SOX10 in the maintenance of the postnatal melanocyte lineage and the differentiation of melanocyte stem cell progenitors. PLOS Genetics; 9(7):e1003644.

4. Shakhova O and Sommer L (2012). Testing the cancer stem cell hypothesis in melanoma: the clinics will tell. Cancer Letters. Sep 10;338(1):74-81.

5. Shakhova O, Zingg D, Schaefer SM, Hari L, Civenni G, Blunschi J, Claudinot S, Okoniewski M, Beermann F, Mihic-Probst D, Moch H, Wegner M, Dummer R, Barrandon Y, Cinelli P, Sommer L (2012). Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma. Nat Cell Biol. 14(8):882-90.

6. Shakhova O, Sommer L. (2010) Neural crest-derived stem cells. StemBook, Cambridge (MA): Harvard Stem Cell Institute; 2010 May 4.