Research
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.
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.
Genomic Instability and Redox Homeostasis in Neurodegeneration
Defects in single genes classified as DNA repair genes can often lead to severe neurological disorders during aging, but the mechanistic basis of this connection is obscure, constituting a major gap in our understanding of human disease. The long-term goal of our research is to understand how defective DNA repair can lead to impaired redox homeostasis via mitochondrial dysfunction in age-related neurobehavioral deficits. Our objective is to gain mechanistic insights into how deletion of the DNA repair proteins leads to damage in the brain. These studies have fundamental relevance to several human diseases including Ataxia Telangiectasia (AT), Parkinson’s disease (PD), and Alzheimer’s disease (AD).
Defects in single genes classified as DNA repair genes can often lead to severe neurological disorders during aging, but the mechanistic basis of this connection is obscure, constituting a major gap in our understanding of human disease. The long-term goal of our research is to understand how defective DNA repair can lead to impaired redox homeostasis via mitochondrial dysfunction in age-related neurobehavioral deficits. Our objective is to gain mechanistic insights into how deletion of the DNA repair proteins leads to damage in the brain. These studies have fundamental relevance to several human diseases including Ataxia Telangiectasia (AT), Parkinson’s disease (PD), and Alzheimer’s disease (AD).
Relevant publications
1. Histone H2AX promotes neuronal health by controlling mitochondrial homeostasis.
Weyemi U, Paul BD, Bhattacharya D, Malla AP, Boufraqech M, Harraz MM, Bonner WM, Snyder SH. Proc Natl Acad Sci U S A. 2019 Apr 9;116(15):7471-7476.
2. Histone H2AX deficiency causes neurobehavioral deficits and impaired redox homeostasis.
Weyemi U, Paul BD, Snowman AM, Jailwala P, Nussenzweig A, Bonner WM, Snyder SH. Nat Commun. 2018 Apr 18;9(1):1526
3. 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. Histone H2AX promotes neuronal health by controlling mitochondrial homeostasis.
Weyemi U, Paul BD, Bhattacharya D, Malla AP, Boufraqech M, Harraz MM, Bonner WM, Snyder SH. Proc Natl Acad Sci U S A. 2019 Apr 9;116(15):7471-7476.
2. Histone H2AX deficiency causes neurobehavioral deficits and impaired redox homeostasis.
Weyemi U, Paul BD, Snowman AM, Jailwala P, Nussenzweig A, Bonner WM, Snyder SH. Nat Commun. 2018 Apr 18;9(1):1526
3. 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
Temporary email: sweyemi1@jhmi.edu
