University of Vermont Cancer Center Member Profile
Steven Roberts, PhD
Associate Professor, Microbiology and Molecular Genetics
Full Member
Cancer Cell (CC)
Academic Interests
Mutation and recombination of DNA sequences drive evolutionary processes and are the fundamental cause of human genetic diseases and cancer. Robust DNA repair mechanisms accurately remove the vast majority of DNA lesions. However, in specific cellular contexts, these pathways can be ineffective leading to transient, high levels of genome instability which can be an important driver of human disease. Therefore, I have dedicated my research career to elucidating mechanisms of DNA repair and replication processes, how these processes functionally integrate to limit mutagenesis in cells that results from endogenous and exogenous sources of DNA damage, and ultimately to understanding the etiology of genetic events that promote carcinogenesis.
My research program has focused on characterizing factors that influence the location and frequency of mutation (genomic plasticity) in somatic cells and determining how these processes can promote cancer development and therapeutic relapse. I have thus far addressed this topic through multiple avenues. First, we have begun characterizing the ability of APOBEC family cytidine deaminases to induce genetic alteration in human cells. Second, in collaboration with Dr. John Wyrick’s lab at Washington State University, we have developed methods to map, genome-wide, the position of common mutagenic DNA lesions and correlate regional densities of lesion formation and repair to the density of mutation. We have successfully done this using yeast, human cells, and clinical tumor data. We have utilized these methods for understanding UV induced mutation during melanomagenesis as well as for DNA alkylation damage. Thirdly, we have begun utilizing novel human mutation reporters to investigate mechanisms of transcription-associated mutagenesis and determining how commonly it occurs as a means of genome instability in human cancer. Finally, we have developed computational algorithms to analyze the types of errors made by DNA double-strand break repair processes, which are a known contributors to cancer risk (i.e. BRCA1 and BRCA2 susceptibility genes) and ongoing tumor evolution. These algorithms assess the sequences generated from high throughput next-generation sequencing of amplicons.
Mutation and recombination of DNA sequences drive evolutionary processes and are the fundamental cause of human genetic diseases and cancer. Robust DNA repair mechanisms accurately remove the vast majority of DNA lesions. However, in specific cellular contexts, these pathways can be ineffective leading to transient, high levels of genome instability which can be an important driver of human disease. Therefore, I have dedicated my research career to elucidating mechanisms of DNA repair and replication processes, how these processes functionally integrate to limit mutagenesis in cells that results from endogenous and exogenous sources of DNA damage, and ultimately to understanding the etiology of genetic events that promote carcinogenesis.
My research program has focused on characterizing factors that influence the location and frequency of mutation (genomic plasticity) in somatic cells and determining how these processes can promote cancer development and therapeutic relapse. I have thus far addressed this topic through multiple avenues. First, we have begun characterizing the ability of APOBEC family cytidine deaminases to induce genetic alteration in human cells. Second, in collaboration with Dr. John Wyrick’s lab at Washington State University, we have developed methods to map, genome-wide, the position of common mutagenic DNA lesions and correlate regional densities of lesion formation and repair to the density of mutation. We have successfully done this using yeast, human cells, and clinical tumor data. We have utilized these methods for understanding UV induced mutation during melanomagenesis as well as for DNA alkylation damage. Thirdly, we have begun utilizing novel human mutation reporters to investigate mechanisms of transcription-associated mutagenesis and determining how commonly it occurs as a means of genome instability in human cancer. Finally, we have developed computational algorithms to analyze the types of errors made by DNA double-strand break repair processes, which are a known contributors to cancer risk (i.e. BRCA1 and BRCA2 susceptibility genes) and ongoing tumor evolution. These algorithms assess the sequences generated from high throughput next-generation sequencing of amplicons.