Logo for University of Iowa Health Care This logo represents the University of Iowa Health Care

Emma Hornick

Emma HornickAssistant Research Scientist (Recent change, formally a Postdoctoral Research Scholar)
Email: emma-hornick@uiowa.edu

Lab: Gail Bishop, PhD

 

Research Summary

The Bishop Laboratory studies lymphocyte signaling with a special interest in the adapter molecule TNF Receptor Associated Factor 3 (TRAF3). TRAF3 regulates signaling through many receptors, including the B and T cell antigen receptors, TLRs, and multiple cytokine receptors. Interestingly, TRAF3 has different effects at different receptors within the same cell, and the same receptor among different cells; its activity is highly context-dependent. I have been fortunate to work on TRAF3 in both B and T lymphocytes.  

In T lymphocytes, TRAF3 promotes robust signaling through the T cell receptor; TRAF3-deficient T cells exhibit reduced survival and effector function. In contrast, TRAF3 restrains signaling through the IL-2 receptor in thymic T regulatory cell precursors. My first project was investigation of the role of TRAF3 in T cell type I interferon signaling. I found that TRAF3 interferes with recruitment of the negative regulatory phosphatase, PTPN22, to the type I interferon receptor (IFNAR) complex, thereby potentiating IFNAR signaling. I am currently working to understand how TRAF3 regulates T cell cytokine receptor signaling, particularly as it applies to T helper subset differentiation.  

B cells lacking TRAF3 display dysregulated signaling through several receptors; one of the most prominent phenotypes is their enhanced homeostatic survival. A significant proportion of mice with a B cell-specific TRAF3 deficiency (B-Traf3-/- mice) develop B cell lymphomas as they age, and loss-of-function mutations or deletions in TRAF3 have been found in human B cell malignancies. Very early in life, B-Traf3-/- mice begin to develop manifestations of autoimmune disease, including autoantibodies and immune complex deposition in the kidneys, though the mice appear healthy and behave normally. Our laboratory has already done substantial work describing TRAF3's regulation of pathways increasing autoimmune disease and B lymphoma susceptibility, my projects are focused on furthering our understanding of and preventing these diseases. We recently showed that in B cell lymphoma cell lines, the abundance of TRAF3 protein predicts the susceptibility of these cell lines to inhibition of GSK3, an multi-functional kinase that affects cell growth, survival, and B cell effector function. Our findings have important implications for a GSK3 inhibitor currently in clinical trials for its ability to treat B cell lymphomas. Our work on TRAF3 has also taken on increased importance with the recent description of multiple families with different heterozygous loss-of-function mutations in TRAF3. The clinical features of "TRAF3 haploinsufficiency" are very similar to phenotypes of B and T cell-specific TRAF3 mice, highlighting the human relevance of this work.