Our research interests are centered on investigating the molecular mechanisms underlying inflammatory arthritis and osteolysis. Our laboratory has made significant contributions for understanding the role of the transcription factor NF-kB in inflammatory bone erosion associated with rheumatoid arthritis and inflammatory osteolysis. Using tissue-specific deletions, we have delineated the role of IKKb and NEMO/IKKg in skeletal development and bone pathologies. We have also discovered that knock-in of constitutively active IKKb in mice causes osteolysis independent of RANK/RANKL upstream signaling. Recently, we have shown that constitutively active IKKb causes inflammatory osteolysis and osteopenia associated with intestinal colitis and inhibits bone formation.
We are currently focused on investigating the role of NF-kB as a link between intestinal inflammation and skeletal wasting as well as between synovial inflammation and joint destruction. Other aspects of ongoing research are focused on the role of NF-kB as central mediator of osteoimmunology (cross talk between the immune system and the skeleton).
This project utilizes gene knock out and knock-in approaches to investigate the role of IKKb in bone under normal and pathologic conditions.
We are using tissue-specific deletion of TAK1 at various stages of myeloid lineage development and its impact on skeletal development.
A NEMO-floxed mouse model is being used to delineate the role of this gene in bone tissue and examine its molecular contribution to bone pathologies with emphasis on particular domains essential for poly-ubiquitinations.
This project is aimed at studying the poorly defined impact of low grade systemic/chronic inflammation on bone health. Two models in which intestinal inflammation is established through intestine-specific expression of constitutively active IKKb or deletion of NEMO are being utilized.
This project utilizes appropriate gene knockout mice to investigate novel aspects of NF-kB contribution to the mechanism by which the forkhead transcription factor, FoxP3 (which is expressed by immune T reg cells), regulates bone homeostasis.
We have discovered recently that orthopedic particles released from implants induce osteolysis through mechanisms involving poly-ubiquitination events. Our current research in this area utilizes relevant transgenic mice to elucidate these mechanisms.
