George P. Souroullas, Ph.D.

Assistant Professor
Internal Medicine

Cancer Biology Program
Molecular Genetics and Genomics Program
Molecular Cell Biology Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-362-8967

  • 314-362-8910

  • 314-747-2797

  • Room 558, McDonnell Sciences Building, 4565 McKinley Av., St. Louis, MO 63110

  • george.souroullas@wustl.edu

  • https://sites.wustl.edu/souroullaslab/

  • @SouroullasLab

  • Epigenetics, chromatin, cancer, mouse models, lymphoma, melanoma, EZH2, PRC2, H3K27me3

  • Understand how epigenetic mechanisms and chromatin dynamics contribute towards the development of cancer.

Research Abstract:

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


Mentorship and Commitment to Diversity Statement:

In the Souroullas Lab we are committed to providing an environment that supports the trainees' professional growth and development and an environment where they can thrive.  

For a detailed description of our lab philosophy, please visit our website here:



Selected Publications:

Souroullas GP, Fedoriw Y, Staudt LM, Sharpless NE. Lkb1 deletion in murine B lymphocytes promotes cell death and cancer. Experimental Hematology. 2017 Jul;51:63-70.e1. PubMed PMID: 28435024.

Souroullas GP, Jeck WR, Parker JS, Simon JM, Liu JY, Paulk J, Xiong J, Clark KS, Fedoriw Y, Qi J, Burd CE, Bradner JE, Sharpless NE. An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation. Nature Medicine. 2016 Jun;22(6):632-40. PubMed PMID: 27135738; PubMed Central PMCID: PMC4899144.

Souroullas GP, Sharpless NE. mTOR signaling in melanoma: oncogene-induced pseudo-senescence?. Cancer Cell. 2015 Jan 12;27(1):3-5. PubMed PMID: 25584887.

Burd CE, Liu W, Huynh MV, Waqas MA, Gillahan JE, Clark KS, Fu K, Martin BL, Jeck WR, Souroullas GP, Darr DB, Zedek DC, Miley MJ, Baguley BC, Campbell SL, Sharpless NE. Mutation-specific RAS oncogenicity explains NRAS codon 61 selection in melanoma. Cancer Discovery. 2014 Dec;4(12):1418-29. PubMed PMID: 25252692; PubMed Central PMCID: PMC4258185.

Kahle JJ*, Souroullas GP*, Yu P, Zohren F, Lee Y, Shaw CA, Zoghbi HY, Goodell MA. Ataxin1L is a regulator of HSC function highlighting the utility of cross-tissue comparisons for gene discovery. PLoS Genetics. 2013 Mar;9(3):e1003359. PubMed PMID: 23555280; PubMed Central PMCID: PMC3610904. *equal contribution

Zohren F, Souroullas GP, Luo M, Gerdemann U, Imperato MR, Wilson NK, Göttgens B, Lukov GL, Goodell MA. The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors. Nature Immunology. 2012 Jul 8;13(8):761-9. PubMed PMID: 22772404; PubMed Central PMCID: PMC3411897.

Souroullas GP, Goodell MA. A new allele of Lyl1 confirms its important role in hematopoietic stem cell function. Genesis. 2011 Jun;49(6):441-8. PubMed PMID: 21387538; PubMed Central PMCID: PMC3115471.

Lukov GL, Rossi L, Souroullas GP, Mao R, Goodell MA. The expansion of T-cells and hematopoietic progenitors as a result of overexpression of the lymphoblastic leukemia gene, Lyl1 can support leukemia formation. Leukemia Research. 2011 Mar;35(3):405-12. PubMed PMID: 20705338; PubMed Central PMCID: PMC2980862.

Souroullas GP, Salmon JM, Sablitzky F, Curtis DJ, Goodell MA. Adult hematopoietic stem and progenitor cells require either Lyl1 or Scl for survival. Cell Stem Cell. 2009 Feb 6;4(2):180-6. PubMed PMID: 19200805; PubMed Central PMCID: PMC2672304.

Last Updated: 4/2/2021 2:46:04 PM

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