Alexandra Whiteley

  • Assistant Professor
  • BIOCHEMISTRY
Alexandra Whiteley

The ubiquitin-proteasome system is essential to eukaryotic life through the regulation of protein degradation. Ubiquilins (Ubqlns) facilitate proteasomal degradation of a poorly defined subset of proteins by physically linking the proteasome with protein bound for degradation. While the molecular mechanism of Ubqln function is unclear, they play an unmistakable role in maintaining human health. In particular, mutations in Ubqln2, which is highly expressed in neurons and muscle, were recently identified as the cause of an X-linked, dominant form of familial Amyotrophic Lateral Sclerosis (fALS).

My laboratory has focused on determining the so-called 'clients' of Ubqln2 in the context of ALS and how their accumulation contributes to disease. We have found that Ubqln2 regulates the abundance of a unique virus-like protein which changes gene expression when over expressed. In light of our research, many questions remain, including the biochemical properties of Ubqln client proteins, the uniqueness of different Ubqln genes, and the mechanism of disease caused by client buildup. My laboratory aims to address these crucial questions using biochemical, cell biological, and in vivo methods.

Selected Publications:

1.     Campodonico, W., Mohan, H.M., Huynh, P.T., Black, H.H., Lau, C.I., Paulson, H.L., Sharkey, L.M., Whiteley, A.M. (2024) The gag-like gene RTL8 antagonizes PEG10-mediated virus like particles. PLoS One 19(12):e0310946. 

2.     Black, H.H.*, Hanson, J.L.*, Roberts, J.E., Leslie, S.N., Campodonico, W., Ebmeier, C.E., Holling, G.A., Tay, J.W., Matthews, A.M., Ung, E., Lau, C.I., Whiteley, A.M. (2023) UBQLN2 restrains the domesticated retrotransposon PEG10 to promote neuronal health in ALS. eLife, 2023 Mar 23;12, pii:e79452. PMCID: PMC10076021.

3.     Whiteley, A.M.*, Prado, M.A.*, de Poot, S.A.H., Paulo, J.A., Ashton, M., et al. (2021) Global proteomics of Ubqln2-based murine models of ALS. Journal of Biological Chemistry, 296, 100153. PMCID: PMC7873701.

4.     Whiteley, A.M., Prado, M.A., Peng, I., Abbas, A.R., Haley, B., et al. (2017) Ubiquilin1 promotes antigen-receptor mediated proliferation by eliminating mislocalized mitochondrial proteins. eLife, 2017 Sep 21;6, pii: e26435. PMCID: PMC5608509.