Within the research area of molecular toxicology, my specific interest and expertise lies in the role that DNA repair and DNA replication of endogenous and environmentally induced DNA damage play in diseases of the central nervous system. Cells of the human body are continuously exposed to agents that damage their DNA; this damage can lead to altered transcription of genes and, in dividing cells, permanent genetic alterations. For genotoxic compounds, cells possess defense mechanisms that include networks of DNA damage response proteins along with enzymes that directly repair or replicate damaged DNA. While DNA damage and its related cellular stress response and repair systems have long been studied with respect to cancer, their importance in neurodegenerative disease has only recently become appreciated. DNA damage appears to contribute to neurodegeneration.
Neural stem and progenitor cells play an essential role in both the developing embryonic and the adult nervous systems where the capacity for self-renewal and proliferation may be important for the normal function of the CNS, such as in learning and memory, as well as in the response to injury. Neural stem and progenitor cells possess DNA damage responses and utilize DNA repair mechanisms that are dramatically and unpredictably different from those in other cell types in the brain and elsewhere. Moreover, these cells are exquisitely sensitive to certain DNA-damaging agents. An emerging area of research is beginning to examine the particular role of neural stem cells, and damage to mitochondrial as distinct from nuclear DNA, in the molecular mechanism of neurodegeneration. DNA repair is a potential risk factor under study in my laboratory.