My laboratory is focused on unraveling the complex regulatory mechanisms that govern the activity of the pleiotropic transcription factor nuclear factor-κB (NF-κB), with the long-term goal of identifying pharmacological intervention points along the NF-κB signaling module. Because of the numerous genes that NF-κB transactivates, particularly those that encode pro-inflammatory, pro-survival and pro-cell cycle proteins, the link between deregulated NF-κB activity and disease has become increasingly evident. For instance, the sustained activation of NF-κB can lead to increased expression of numerous pro-inflammatory cytokines and ultimately to chronic inflammation, which promotes the development and progression of cancer. In addition to the promotion of tumorigenesis, deregulation of NF-κB contributes to autoimmune and inflammatory diseases, including ulcerative colitis and rheumatoid arthritis. NF-κB is composed of five different subunits, c-Rel, RelA (p65), RelB, p50/p105 (NF-κB1) and p52/p100 (NF-κB2), that homo- or heterodimerize to form functional transactivating complexes.
We have uncovered a mechanism of tumor necrosis factor receptor (TNFR)-dependent NF-κB activation that is regulated by the aryl hydrocarbon nuclear translocator (ARNT; also known as hypoxia-inducible factor 1-beta). ARNT is a transcription factor that is integral in the regulation of xenobiotic and hypoxic responses but had not been previously shown as a component of NF-κB signaling. Our current focus is whether NF-κB regulation via ARNT is augmented in lymphoid malignancies, many of which express a certain isoform of ARNT that can be inactivated via phosphorylation.
Other interests in the laboratory include investigations of the NF-κB p52/p100 subunit as a suppressor of cell-cycle inhibitory genes and characterizing novel TNFR-interacting proteins that function at the level of the plasma membrane to activate NF-κB.
Pharmacology & Toxicology
College of Pharmacy
The University of Texas
107 W. Dean Keeton
Austin, TX, USA
Email Address: pharmtox
"Drugs, the Brain and Behavior" is co-authored by Dr. Carlton Erickson, the college's associate dean for research and graduate studies, and Dr. John Brick, executive director of Intoxikon International.
Andrea Gore is named to the SEBM Distinguished Scientist Award.