Catherine Kerr
- Former Trainee
- MOLECULAR BIOSCIENCES
Contact Info
1200 Sunnyside Avenue
Lawrence, KS 66045
Research —
ADP-ribosylation is a common post-translational modification catalyzed by ADP-ribosyltransferases (ARTs), also known as PARPs. ADP-ribosylation impacts many areas of cell biology, including virus infections and innate immunity. Most of the 17 mammalian PARPs are interferon-stimulated genes (ISGs), further indicating their role in the anti-viral response. PARP activity can be reversed by ADP-riboslyhydrolases (ARHs), and several families of viruses, including coronaviruses (CoVs), encode for ARH enzymes. Using the model CoV, murine hepatitis virus (MHV) we recently found that PARP activity restricts the replication of an ARH-deficient (ARH-) MHV in bone-marrow-derived macrophages (BMDMs). An siRNA screen of PARPs revealed that the knockdown of PARP12 partially restored the replication of the ARH- MHV while having no impact on wild-type virus. To confirm these results and test the role of PARP12 viral pathogenesis, we generated PARP12-/- mice. While there was little effect on the replication of WT virus, ARH- MHV replication was significantly enhanced in PARP12-/- BMDMs. We hypothesized that these mice might be more susceptible to infection with the ARH- MHV virus than WT virus. However, there were no significant differences in weight loss or survival between WT, PARP12+/-, or PARP12-/- infected with ARH- MHV. This data suggests that other PARPs are likely able to compensate for the lack of PARP12 in vivo. To gain further insight into the molecular function of PARP12, we are analyzing the localization of PARP12 in BMDMs, testing how it impacts the viral lifecycle and are developing tools to identify PARP12 interacting partners.
Selected Publications —
- Voth LS, O'Connor JJ, Kerr CM, Doerger E, Schwarting N, Sperstad P, Johnson DK, Fehr AR (2021). Unique mutations in the murine hepatitis virus macrodomain differentially attenuate virus replication, indicating multiple roles for the macrodomain in coronavirus republican. J Virol. 95(15). Epub 2021.
- Voth LS, O'Connor JJ, Kerr CM, Doerger E, Schwarting N, Sperstad P, Johnson DK, Fehr AR (2021). An MHV macrodomain mutant predicted to lack ADP-ribose binding activity is severely attenuated, indicating multiple roles for the macrodomain in coronavirus republication. bioRxiv. 2021. Preprint.PMID.
- Fehr AR, Singh SA, Kerr CM, Mukai S, Higashi H, Aikawa M (2020). The impact of PARPs and ADP-ribosylation on inflammation and host-pathogen interactions.Genes Dev. 34(5-6):341-359.
- McAllister CT, Motriuk-Smith D, Kerr CM (2018). Three new coccidians (cyclospora, eimeria) from eastern moles, scalopus aquaticus (linnaeus) (mammalia: soricomorpha: talpidae) from Arkansas, USA.Systematic Parasitology 95, 271.
- McAllister CT, Motriuk-Smith D , Kerr CM, Carmen KN, Seville RS, Connior MB (2017). A new eimerian (Apicomplexa: Eimeriidae), from ornate box turtle, Terrapene ornata (Agassiz) (Testudines: Emydidae) from northwest Arkansas, USA. Systematic Parasitology 94(2):293-298. Epub 2017 Jan 27.