George Souroullas

Assistant Professor of Medicine

    • 366 Citations
    20032019

    Research output per year

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    Personal profile

    Research interests

    The Souroullas Lab is studying the role of epigenetic mechanisms during cancer development, with a specific interest in hematopoietic/lymphoid malignancies and melanoma. Epigenetic regulation is a very dynamic process which involves three main components: (1) Writers: These are proteins which catalyze the addition of chemical groups on the DNA or chromatin, (2) Readers: Proteins which recognize these chemical groups, interact with them, interpret them and transmit further downstream signals. (3) Erasers: Proteins that recognize these marks and catalyze their removal (Fig. 1). Under homeostatic conditions, these epigenetic mechanisms can directly regulate fundamental processes within the cell, such as DNA transcription, replication, repair, cell identity, growth and proliferation. These cellular processes are commonly implicated and deregulated in cancer. Furthermore, recent next generation sequencing studies have identified mutations in many epigenetic factors in multiple cancers, suggesting that epigenetics must play an important role during cancer development. The reversible nature of the activity of these proteins presents us with an incredible opportunity in translational medicine. Understanding the phenotypic and molecular consequences of epigenetic dysregulation during carcinogenesis remains a challenge, but it is critical in developing more effective therapeutic strategies. Our lab is interested in exploring how epigenetic mechanisms and chromatin dynamics contribute towards the development of cancer (Fig. 2). Towards that end, we utilize genetically engineered mouse models in combination with molecular, biochemical, and pharmacological approaches. Overall, our goal, is to explore how epigenetic mechanisms interact under homeostatic conditions, how those interactions are perturbed in cancer, how they interact with other oncogenic/genetic events and how we can take advantage of this knowledge to design more effective therapeutic strategies. Current projects in the lab are focused on the suppressive chromatin mark H3K27me3, which is deposited by the PRC2 complex and its catalytic subunit, EZH2. We are specifically interested in the role of EZH2 Y641 mutations during the development of B cell lymphoma and melanoma because of the high incidence of these mutations in these two cancers. Ongoing projects in the lab include: • Understand how mutations in EZH2 change the chromatin landscape and explore how these chromatin changes determine deposition and interpretation of other chromatin marks • Investigation of the downstream effects of the neomorphic EZH2 Y641 mutations in B cell lymphoma and melanoma • Understand the genetic and molecular interactions between mutations in EZH2 and other oncogenic events

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    Research Output

    • 366 Citations
    • 12 Article
    • 1 Comment/debate
    • 1 Short survey

    Cells exhibiting strong p16 INK4a promoter activation in vivo display features of senescence

    Liu, J. Y., Souroullas, G. P., Diekman, B. O., Krishnamurthy, J., Hall, B. M., Sorrentino, J. A., Parker, J. S., Sessions, G. A., Gudkov, A. V. & Sharpless, N. E., Feb 12 2019, In : Proceedings of the National Academy of Sciences of the United States of America. 116, 7, p. 2603-2611 9 p.

    Research output: Contribution to journalArticle

    Open Access
  • 33 Scopus citations
  • Lkb1 deletion in murine B lymphocytes promotes cell death and cancer

    Souroullas, G. P., Fedoriw, Y., Staudt, L. M. & Sharpless, N. E., Jul 2017, In : Experimental Hematology. 51, p. 63-70.e1

    Research output: Contribution to journalArticle

  • 4 Scopus citations

    An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation

    Souroullas, G. P., Jeck, W. R., Parker, J. S., Simon, J. M., Liu, J. Y., Paulk, J., Xiong, J., Clark, K. S., Fedoriw, Y., Qi, J., Burd, C. E., Bradner, J. E. & Sharpless, N. E., Jun 1 2016, In : Nature medicine. 22, 6, p. 632-640 9 p.

    Research output: Contribution to journalArticle

  • 83 Scopus citations

    Comparison of cesium-137 and X-ray irradiators by using bone marrow transplant reconstitution in C57BL/6J mice

    Gibson, B. W., Boles, N. C., Souroullas, G. P., Herron, A. J., Fraley, J. K., Schwiebert, R. S., Sharp, J. J. & Goodell, M. A., Jun 1 2015, In : Comparative medicine. 65, 3, p. 165-172 8 p.

    Research output: Contribution to journalArticle

  • 7 Scopus citations