- Diseases linked to genome maintenance and stability
- Molecular mechanisms underlying chronic inflammatory diseases
DNA is continuously exposed to damaging/mutagenic agents through both normal cellular processes and environmental exposures. As a result of these events, hundreds of thousands of lesions per cell per day can be produced. DNA mutations can affect the cellís ability to transcribe genes, produce transforming mutations, or induce programmed cell death. In spite of these numerous insults, the DNA in our genomes are remarkably stable due to highly efficient mechanisms for recognizing and repairing this damage.
The SCMM DNA repair and mutagenesis research program focuses on key mechanisms for repair of damaged DNA and cellular responses to it. These programs include:
- Identification of mechanisms and proteins responsible for post-replicative bypass of damaged DNA;
- The proteins and mechanisms involved in translesion DNA synthesis in eukaryotes;
- Mechanisms for oxidative DNA damage repair, its regulation, and its impact on apoptosis and drug resistance of tumor cells.
These programs will have impact our understanding of cellular mechanisms underlying mutagenesis in cancer, aging, and neurodegenerative diseases.
Inflammation is an essential and beneficial host reponse to infection, injury or trauma. Here, cytokines, lipids and reactive oxygen species (ROS) generated by exposed tissues signal for recruitment of leukocytes to respond to the threat. However, it is now recognized that many common human diseases have underlying features of chronic inflammation that underly or exacerbate the disease. For example, atopic asthma, viral induced wheezing, atherosclerosis, diabetes mellitus, inflammatory bowel disease and others have a chronic inflammatory component. In fact, targeting underlying inflammation has revolutionized the treatment of asthma and atherosclerosis.
The SCMM inflammation biology program investigates the molecular mechanisms for inflammation in airway and cardiovascular systems. These include:
- The role of chemokines in viral-induced pediatric airway disease;
- The mechanisms for viral induced airway inflammation;
- The mechanisms in severe asthma unresponsive to conventional glucocorticoid treatment;
- Mechanisms for activation of cytokine receptors;
- The structure and signaling mechanisms for glucocorticoid receptor;
- The role of mitochondrial ROS in allergic sensitization.
These programs will identify novel mechanisms for inflammation induced human disease and new methods for manipulating the underlying inflammation.