Research interests:
Inflammation is a genetically programmed response to cellular stress that can be activated by a number of mechanisms, including induction of transcription of critical genes. NF-κB is a highly conserved transcription factor that plays a pivotal role in the transcriptional activation of this stress response and has been intimately linked to a range of human maladies including autoimmune disorders and cancer. Therefore, the regulation of this transcription factor is of critical importance for normal physiology and disease. Our work has identified specific pathways for the termination of NF-kB mediated transcription that involve the ubiquitination and proteasomal degradation of this transcription factor. The two main areas of study in our lab at the moment are:
1) COMMD proteins and pro-inflammatory signaling: Our studies on the mechanisms of IAP-mediated signaling events led to the identification of the COMMD protein family, a group of factors defined by the presence of unique protein domain. This family is highly conserved with ten COMMD genes being present in the genomes of organisms ranging from protozoa to humans. COMMD1, the prototype member of this family, inhibits NF-kB in the nucleus where it is recruited to gene promoter sites and facilitates the release of chromatin-bound NF-kB subunits by promoting their ubiquitination. We currently study the regulation of COMMD-mediated ubiquitination of NF-kB, the involvement of additional co-factors, and the functional consequences of ubiquitination on the activity of NF-kB at the cellular level. In addition, animal models of COMMD deficiency are being employed to examine the role of COMMD-mediated ubiquitination in the regulation of inflammation in vivo.
2) COMMD proteins and the ubiquitination machinery: We have identified that COMMD proteins play a more general role in the ubiquitination of cellular factors through their ability to interact with ubiquitin ligases of the Cullin family. We are investigating the nature of such interactions and their functional consequence on the activity of Cullin-containing ligases. In addition, we are investigating the involvement of COMMD proteins in the regulation of other targets by coupling biochemical and genetic approaches.
Positions available:
NF-kB regulation, ubiquitination and inflammatory responses in mouse models (93)
The Department of Internal Medicine, Division of Digestive and Liver Diseases, has a post-doctoral position available to study NF-kB regulation, ubiquitination and inflammatory responses in mouse models. Laboratory is focused on the ubiquitination of NF-kB/RelA and its role in inflammatory responses (EMBO Journal, 26: 459-467, 2007; Genes & Development, 23: 849-861, 2009). Candidates with PhD or equivalent degree and a demonstrated track record in molecular biology, and mouse models of inflammation are preferred.
Send complete curriculum vitae and three references to:
Dr. Ezra Burstein
University of Texas Southwestern Medical Center
5323 Harry Hines Blvd.
Dallas, TX 75230-9151
ezra.burstein@utsouthwestern.edu
Contact Information:
UT Southwestern Medical Center
5323 Harry Hines Boulevard
Room J5.126
Dallas, Texas 75230-9151
Telephone: 214-648-8005
Facsimile: 214-648-2022
