Research Interest 1
Genomic instability, Epithelial Differentiation and Redox Homeostasis in Cancer
The majority of human cancers arise from epithelial tissues, and the epithelial-to-mesenchymal transition (EMT) is thought to be an essential event for cancer progression from a primary tumor to becoming metastatic. While genomic instability and defective mitochondrial homeostasis are widely described as integral for cancer progression, how these two phenomena interact is poorly understood. Thus, cancer cells exhibiting genomic instability may utilize mitochondrial metabolism to proliferate in a nutrient-poor tumor microenvironment and to seed tumors in distant organs (i.e. metastasize). Investigating these links is conceptually innovative and may provide novel insights into the complex interactions between genomic instability, epithelial differentiation, redox homeostasis and metastasis.
The majority of human cancers arise from epithelial tissues, and the epithelial-to-mesenchymal transition (EMT) is thought to be an essential event for cancer progression from a primary tumor to becoming metastatic. While genomic instability and defective mitochondrial homeostasis are widely described as integral for cancer progression, how these two phenomena interact is poorly understood. Thus, cancer cells exhibiting genomic instability may utilize mitochondrial metabolism to proliferate in a nutrient-poor tumor microenvironment and to seed tumors in distant organs (i.e. metastasize). Investigating these links is conceptually innovative and may provide novel insights into the complex interactions between genomic instability, epithelial differentiation, redox homeostasis and metastasis.
Figure: Hypothetical model for the role of H2A.X in the transcriptional regulation of Slug and ZEB1 during EMT in colon cancer cells. H2A.X removal from the nucleosome leads to enhanced enrichment of active chromatin marks (H3K9ac) within the promoters of Slug and ZEB1. This chromatin configuration enables the transcriptional activation of Slug and ZEB1. Elevated levels of Slug and ZEB1 are key in mediating the expression of several EMT-related genes.
Relevant Publications:
1. The histone variant H2A.X is a regulator of the epithelial-mesenchymal transition.
Weyemi U, Redon CE, Choudhuri R, Aziz T, Maeda D, Boufraqech M, Parekh PR, Sethi TK, Kasoji M, Abrams N, Merchant A, Rajapakse VN, Bonner WM.
Nat Commun. 2016 Feb 15;7:10711. doi: 10.1038/ncomms10711.
2. NADPH oxidase 4 is a critical mediator in Ataxia telangiectasia disease
Weyemi U, Redon CE, Aziz T, Choudhuri R, Maeda D, Parekh PR, Bonner MY, Arbiser JL, Bonner WM. Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2121-6. doi: 10.1073/pnas.1418139112. Epub 2015 Feb 2.
1. The histone variant H2A.X is a regulator of the epithelial-mesenchymal transition.
Weyemi U, Redon CE, Choudhuri R, Aziz T, Maeda D, Boufraqech M, Parekh PR, Sethi TK, Kasoji M, Abrams N, Merchant A, Rajapakse VN, Bonner WM.
Nat Commun. 2016 Feb 15;7:10711. doi: 10.1038/ncomms10711.
2. NADPH oxidase 4 is a critical mediator in Ataxia telangiectasia disease
Weyemi U, Redon CE, Aziz T, Choudhuri R, Maeda D, Parekh PR, Bonner MY, Arbiser JL, Bonner WM. Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2121-6. doi: 10.1073/pnas.1418139112. Epub 2015 Feb 2.
University of Texas at Austin
Institute for Cellular and Molecular Biology
Department of Molecular Biosciences
100 E 24th St
Austin, TX 78712 USA
Email: urbain.weyemi@austin.utexas.edu
