Wright, Casey, Ph.D.
Assistant Professor
PHR 5.224B
512-232-8331
cww@mail.utexas.edu

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 disrupted during exposure to xenobiotics, such as dioxin, which might result in altered NF-κB activity and in turn reveal possible links between toxicant exposure and tumorigenesis. 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.