Casey W WrightAdjunct/Clinical Affiliate
College of Pharmacycww@austin.utexas.edu
My laboratory is focused on understanding the regulatory mechanisms of the pleiotropic transcription factor nuclear factor-kappaB (NF-kB), with the long-term goal of identifying pharmacological intervention points along the NF-kB signaling module. The sustained activation of NF-kB can lead to increased expression of numerous pro-inflammatory cytokines and ultimately to chronic inflammation, which promotes the development of numerous autoimmune and inflammatory diseases including ulcerative colitis, rheumatoid arthritis, and cancer. We have uncovered a novel mechanism of tumor necrosis factor receptor (TNFR)-dependent NF-kB activation that is regulated by the xenobiotic and hypoxic responsive transcription factor, aryl hydrocarbon nuclear translocator (ARNT). Our current focus is on characterizing the different roles of the ARNT isoforms in cancer growth through their modulation of NF-kB and the tumor suppressor p53. Other interests in the laboratory include investigations into the auto-regulation of the NF-kB inducing kinase (NIK) and how NIK regulates the tumor suppressor PTEN.
The TRAF3 adaptor protein drives proliferation of anaplastic large cell lymphoma cells by regulating multiple signaling pathways. (2014) Cell Cycle 13, 1918-1926.
BH3-only protein BIM mediates heat shock-induced apoptosis. (2014) Plos One 9(1): e84388.
NF-kB-inducing kinase (NIK) contains an amino terminal inhibitor of apoptosis (IAP) binding motif (IBM) that potentiates NIK degradation by c-IAP1. (2014) Journal of Biological Chemistry 289, 30680-30689.
The aryl hydrocarbon nuclear translocator alters CD30-mediated NF-kB-dependent transcription. (2009) Science 323, 251-255.
Two distinct signaling cascades target the NF-kB regulatory factor c-IAP1 for degradation (2009) Biochemical Journal 420, 83-91.
Cytoprotective effects of IAPS revealed by a small molecule IAP antagonist (2009) Biochemical Journal 417, 765-771.
New Insights into the Function of IAP Proteins: Modulation of the Myc/Max/Mad Network (2008) Developmental Cell 14, 3-4.
Apoptotic sensitivity of murine IAP-deficient cells (2008) Biochemical Journal 415, 21-25.
CD30 activates both the canonical and alternative NF-kB pathways in anaplastic large cell lymphoma cells. (2007) Journal of Biological Chemistry 282, 10252-10262.
Re-awakening the cellular death program in neoplasia through the therapeutic blockade of IAP function. (2005) Journal of Clinical Investigation 115, 2673-2378.
- Gardella, Kacie
- Lee, Sunhee