Our research interest lies in understanding the intricate relationship between the poly(ADP-ribose) polymerase-1 (PARP-1) and related factors and oxidative stress during inflammation with a specific focus on the mechanism(s) by which PARP-1 contributes to the regulation of inflammatory genes and promotes pathological outcomes. Our long term goal is to use our findings as a basis for the development of new and improved approaches to treat or prevent inflammatory diseases that involve oxidant stress and PARP-1 activation. We use an integrative approach in our studies, which involve animal models, human specimens, ex vivo systems, adoptive transfers, primary cell culture systems and cell-free methods. Within these systems, we apply pathology and associated techniques as well as state-of-the-art molecular methods, such as cell imaging, fluorescence resonance energy transfer (FRET), protein-protein interaction assays, and conditional expression systems. These approaches allow us to address the complexity of these inflammatory diseases and, ultimately, attain reliable data from which to draw solid conclusions. We focus primarily on three disease models which include asthma, atherosclerosis, and colon cancer. Studying these three diseases, which have a number of similarities and dissimilarities, provides us with unique opportunities to address critical questions and explore lines of inquiry that would not be possible or obvious when studying only one of these diseases.
- Mechanisms by which poly(ADP-ribose) polymerase (PARP)-1 participates in inflammatory diseases such as asthma and atherosclerosis.
- Role of PARP-1 in genomic stability and inflammation in colon cancer.
- Role of DNA-dependent kinase (DNA-PK) in regulating inflammation and associated transcription factors primarily NF-kB.