Lynn Harrison, Ph.D.
Ph.D. 1991, University of Manchester, England
Department of Molecular and Cellular Physiology
LSU Health Sciences Center
1501 Kings Highway
Shreveport, LA 71130
A wide variety of oxidative DNA damage is introduced into nuclear and mitochondrial DNA by reactive oxygen species (ROS). Sources of ROS include cellular metabolism, inflammation and exogenous agents used in the treatment of cancer such as ionizing radiation. Astronauts can also be exposed to high energy radiation during space flight. If DNA damage is not repaired or is mis-repaired, it can result in mutations, chromosomal aberrations or cell death. In fact DNA damage has been implicated in multistage carcinogenesis and aging. DNA repair is therefore important for the maintenance of genetic integrity and stability, and cell survival. This laboratory works on two projects:
Radiotherapy introduces clusters of DNA lesions, which can cause incomplete repair and the generation of lethal double-strand breaks. We want to identify repair enzymes that can generate lethal double-strand breaks from radiation DNA damage and determine whether it is possible to manipulate the DNA repair system in a tumor during radiotherapy to enhance tumor cell killing. We are also using a bacterial protein to try to block tumor cell DNA repair in the mitochondria to test whether mitochondrial DNA repair is important for cell survival.
Mycobacteria exist in our environment and can result in human disease. M. tuberculosis causes tuberculosis. Other pathogenic mycobacteria such as M. avium can live in water and can also cause lung infections. M. marinum is also water-borne and infects fish but has the same pathology as other pathogenic mycobacteria. Since M. marinum grows at a lower temperature it is less infectious to humans and can cause skin infections. It is therefore a safer model to study the pathogenicity of mycobacteria. It has been determined that certain bacteria are more infectious when grown under microgravity. This is a concern for astronauts on the International Space Station and for possible future long space flight missions. We are using M. marinum as a model to study the effect of microgravity on water-borne mycobacteria. Gene expression and resistance to oxidative stress, as well as infection of macrophage cells are being studied. Mycobacteria also have a specific DNA repair pathway (non-homologous end-joining) that may be important for bacterial survival during persistent infection. We are interested in whether the repair of DNA double-strand breaks is important for the pathogenicity of mycobacteria. My lab have cloned the M. marinum DNA repair genes involved in the end-joining pathway and want to examine their biological importance.