Center for Genomic Integrity

The Molecular and Cellular Biology Branch (MCBB) investigates various molecular mechanisms affecting genomic integrity including DNA replication, DNA repair, recombination, and the DNA damage response. We use molecular, cellular biological and biochemical approaches to understand the detailed molecular mechanisms that ensure genomic integrity. MCBB focuses on DNA replication during normal cellular proliferation and upon exposure to genotoxic stress. The branch uses mouse and zebrafish as model organisms to study phenotypes associated with DNA repair deficiency and exposure to genotoxic agents. Lastly, MCBB searches for and characterizes small molecules that inhibit DNA repair pathways. At MCBB multidisciplinary research is focused to work out the molecular mechanisms that prevent tumorigenesis and premature aging. MCBB is engaged in multiple collaborations with national and international laboratories.

Research in the Chemical and Cancer Biology Branch focuses on DNA repair and damage response pathways and their relationship to carcinogenesis and tumor therapy. Biochemical, molecular and cell biology-based studies are combined with organic chemistry to study the mechanistic details of repair pathways dealing with DNA adducts formed by environmental agent and antitumor drugs, double stranded breaks as well as the cellular responses to DNA replication stress. Our studies aim to elucidate the mechanisms of the pathways preventing tumorigenesis and inherited genetic disorders such as xeroderma pigmentosum and Fanconi anemia. We are also interested in how DNA repair capacity in tumors may be assessed and targeted to improve therapeutic outcomes. Our research is inherently multi-disciplinary and involves multiple national and international collaborations.

Research in the Genetic and Genomic Toxicology Branch focuses on understanding basic mechanisms of mutagenesis and on fail-safe mechanisms that ensure faithful genome maintenance and the elimination of compromised cells by programmed cell death. The branch mainly uses C. elegans as an invertebrate model organism and employs advanced genetics, genomics, cell biology and next generation sequencing based approaches. At the same time, we use mammalian cells to translate our insights gained from the invertebrate model. Our studies are relevant for understanding fundamental mechanisms leading to cancer formation and also aimed to better understand and more effectively use a range of agents commonly used for cancer therapy. We are engaged in multiple national and international collaboration and are currently transferring our lab from Scotland to Korea expecting to fully build up our branch by 2021.