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 Wioletta Czaja, Ph.D.
 “Genomic instability underlies many human diseases, including cancer, neurodegeneration and immune dysfunction. In cells, genomic DNA is organized into highly dynamic 3D structure called chromatin. Our research investigates chromatin-based regulation
of DNA repair and genome maintenance. This research is critically important to advance understanding of the molecular events leading to genome instability, and ultimately to facilitate development of
new approaches in disease prevention, diagnosis and treatment.”
Wioletta Czaja
28 | THE HORMEL INSTITUTE // UNIVERSITY OF MINNESOTA DNA Repair and Genome Stability
      SECTION LEADER / ASSISTANT PROFESSOR
Nearly all forms of cancer (~90%) contain significant levels of genomic instability (high frequency of mutations, chromo-
somal rearrangements), largely resulting from deficient or dysregulated DNA repair processes. The molecular events leading to genomic instability are not well understood. We inves- tigate the epigenetic and chromatin-based regulation of DNA damage and repair. We are also developing new methodologies enabling high-resolution genome-wide mapping of dam- aged and modified DNA bases, with the goal
of uncovering novel mechanisms involved in mutagenesis and carcinogenesis. The long-term objective of our research is to understand how stability of the human genome is maintained and regulated in various cellular and tissue contexts. We employ modern approaches in biochemistry, cell and molecular biology, genetics and genom- ics using fungal model organisms and human cell lines.
 Uncovering new mechanisms of HELLS-mediated genome stability and cancer suppression. Our research focuses on investigating the role of human HELLS (Helicase Lymphoid Specific) SNF2 remodeler
in DNA repair and genome maintenance. Mutations in HELLS cause human ICF syndrome (Immunodeficiency, Centromeric Instability, Facial anomalies) and HELLS dysregulation is found in many cancers. In order to better under- stand HELLS-mediated mechanisms of genome stability, we established and validated a fungal
epigenetic model. This work revealed a new, previ- ously unrecognized role for HELLS in cellular responses to DNA alkylation damage and further demonstrated
a critical role for HELLS in the maintenance/repair of heterochromatin domains at centromeres and telo- meres. We aim to define novel, HELLS-mediated
 




















































































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