Kelly Arcipowski has a personal interest in her research about how proteins interact and how those interactions drive cancer.
Cancer affects members of Arcipowski’s family. Her cousin had non-Hodgkin’s lymphoma, a form of cancer that relates to her current research.
Arcipowski, a Ph.D. candidate in molecular and cellular biology, and her mentor, Gail Bishop, studied mouse B cells expressing the viral protein Latent Membrane Protein 1 (LMP1), which has been implicated in several types of cancer because of its role in the proliferation and survival of Epstein-Barr virus infected B cells. They discovered that LMP1 needs the cellular protein Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) to promote its B cell activation signaling pathways.
Their study, published in the Journal of Biological Chemistry in 2011, also shows that LMP1 and CD40 – a normal activating receptor on B cells – both use TRAF6 as a key signaling protein, but in different ways. LMP1 mimics CD40 in delivering activation signals to B cells, but LMP1's signals are amplified and sustained, resulting in B cell hyper-activation.
B cells are a type of white blood cell. They normally mature into plasma cells that produce proteins called antibodies necessary to fight off infections. But in the process of modifying antibody genes, mistakes can cause mutations. With an accumulation of such mutations, B cells can become cancerous, which is why B cell malignancies are relatively common.
"We found that TRAF6 is essential for LMP1 functions, and that it interacts with LMP1 in a way that is distinct from the way in which TRAF6 interacts with CD40," said Arcipowski, the lead author. "Thus, it might be possible to target LMP1 signaling without disrupting normal immune function. This information is valuable to the development of new therapies to target LMP1-mediated pathogenesis, including B cell lymphomas and autoimmune disease."
B-cell lymphomas include Hodgkin's lymphomas and most non-Hodgkin's lymphomas. Examples of autoimmune diseases in which LMP1 is implicated are rheumatoid arthritis and systemic lupus erythematosus (SLE).
Arcipowski currently is researching how TRAF6 is involved in the LMP1 signaling pathway.
"If you figured out exactly which part of TRAF6 was binding to LMP1, you could target that specific interaction while leaving TRAF6's association with CD40 intact," Arcipowski said.
In May 2011, Arcipowski was an invited speaker at the 13th International TNF Conference in Hyogo, Japan. Her presentation was on multiple functions for TRAFs in immune regulation.