Julie Rumble
e-mail address: jrumble@umich.edu

Mentor: Colin Duckett, PhD

Research Description

X-linked inhibitor of apoptosis, or XIAP, has been shown in humans to be a potent regulator of the cell death pathway. Additionally, mutations in XIAP have been identified as a cause of X-linked lymphoproliferative disorder (XLP), a rare but fatal disease associated with aberrant response to Epstein-Barr virus (EBV). Surprisingly, mice that lack XIAP have not thus far been shown to have any major defects. In these studies, I show that cells derived from these mice are more sensitive to apoptotic stimuli than their wildtype counterparts, though only under a restricted range of conditions. I have also found that XIAP-null mice respond differently to a murine gammaherpesvirus closely related to EBV. These studies will not only shed light on the function of XIAP in the regulation of the immune system, but will also help to understand the pathogenesis of XLP.

Publications

Wright CW, Rumble JM , Duckett CS. CD30 activates both the canonical and alternative NF- k B pathways in anaplastic large cell lymphoma cells. J Biol Chem . 2007; 282:10252-62.

Burstein E, Hoberg JE, Wilkinson AS, Rumble JM , Csomos RA, Komarck CM, Maine GN, Wilkinson JC, Mayo MW and Duckett CS. 2005. COMMD proteins, a novel family of structural and functional homologs of MURR1. J Biol Chem . 280:22222-32.

Wilkinson JC, Richter BW, Wilkinson AS, Burstein E, Rumble JM, Balliu B and Duckett CS. 2004. VIAF, a conserved inhibitor of apoptosis (IAP)-interacting factor that modulates caspase activation. J Biol Chem . 279:51091-9.

Abstracts

Rumble JM, Oetjen KA, Wright CW, Stein P, Schwartzberg PL, Moore BB, Duckett CS.: Analysis of XIAP in a murine model of human X-linked lymphoproliferative syndrome: susceptibility to g-herpesvirus infection. Keystone Symposium on Cell Death in the Immune System, Breckenridge CO, February 2008.