Melissa Maginnis

Education

Vanderbilt University, 2007, Ph.D

Research Interests

Research in the Maginnis laboratory is focused on understanding the cellular and molecular basis of viral disease. Specifically, our work seeks to define the viral and host cell factors that regulate infection and viral pathogenesis of the human JC polyomavirus (JCPyV). The majority of the population is infected with JCPyV, which establishes a lifelong, persistent infection in the kidney without symptoms. In immunocompromised hosts, such as individuals receiving immunomodulatory therapies for autoimmune diseases or those with HIV, the virus can spread from the kidney to the central nervous system and cause a lytic infection in the brain. Viral destruction of the glial cells astrocytes and oligodendrocytes, which are critical for myelin production, results in the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). There is currently no effective treatment for PML.

Viruses are complex, yet extremely efficient machines that hijack the host cell machinery to complete an infectious cycle and produce progeny virus. The interplay between JCPyV and host cell factors is critical to understanding disease outcomes and PML pathogenesis. Research in my laboratory is focused on understanding the detailed molecular interactions between the virus and host cell factors that drive the early steps in the infectious cycle including entry, trafficking, and viral transcription. In particular, we are focused on defining how JCPyV uses the serotonin receptor to transverse the plasma membrane, identifying signaling cascades that drive viral transcription, and elucidating how the virus causes persistent and lytic infections. This research will allow us to define key unanswered questions in JCPyV biology, provide crucial insights into JCPyV pathogenesis, and identify novel targets for rational drug design for prevention and treatment of PML.

Visit our lab website: http://umaine.edu/maginnislab/

Selected Publications

• Wilczek, M.P., DuShane, J.K., Armstrong, F.A., and Maginnis, M.S.+ (2020). JC Polyomavirus Infection Reveals Delayed Progression of the Infectious Cycle in Normal Human Astrocytes. Journal of Virology, 94(5): e01331-19. [Cover Illustration]. +, Corresponding author.
• DuShane, J.K., Mayberry, C.L., Wilczek, M.P., Nichols, S.L., and Maginnis, M.S.+ (2019). JCPyV-Induced MAPK Signaling Activates Transcription Factors during Infection.
  International Journal of Molecular Sciences, 20(19):4779. +, Corresponding author.
• DuShane, J.K. and Maginnis, M.S.+ (2019). DNA Virus Exploitation of the MAPK-ERK Cascade. International Journal of Molecular Sciences, 20(14):3427. [Invited Review]. +,
  Corresponding author.
• Assetta, B., Morris-Love, J., Gee, G.V., Atkinson, A., O’Hara, B.A., Maginnis, M.S., Haley, S.A., and Atwood, W.J. (2019). Genetic and Functional Dissection of the Role of Individual
  5-HT2 Receptors as Entry Receptors for JC Polyomavirus. Cell Reports, 27(7):1960-1966.e6.
• DuShane, J.K., Wilczek, M.P., Crocker, M.A., Maginnis, M.S.+ (2019). High-Throughput Characterization of Viral and Cellular Protein Expression Patterns during JC Polyomavirus
  Infection. Frontiers in Microbiology, 10:783. +, Corresponding author.
• Curthoys, N.M., Mlodzianoski, M.J., Parent, M., Butler, M.B., Raut, P., Wallace, J., Lilieholm, J., Mehmood, K., Maginnis, M.S., Waters, H., Busse, B., Zimmerberg, J., and Hess ST.
  (2019). Influenza Hemagglutinin Modulates Phosphatidylinositol 4,5-Bisphosphate Membrane Clustering. Biophysical Journal, 116(5):893-909.
• Mayberry, C.L., Soucy, A.N., Lajoie, C.R., DuShane, J.K., and Maginnis, M.S.+ (2019). JC Polyomavirus Entry by Clathrin-Mediated Endocytosis is Driven by β-arrestin. Journal of
  Virology, 93(8):e01948-18. [Spotlight Article]. +, Corresponding author.
• Maginnis M.S. Virus-Receptor Interactions: The Key to Cellular Invasion. (2018). Journal of Molecular Biology; 430(17) 17:2555-2556.
• DuShane, J.K., Wilczek, M.P., Mayberry, C.L., and Maginnis, M.S. (2018). ERK is a Critical Regulator of JCPyV Infection. Journal of Virology, 14;92(7): pii: e01529-17.
• Mayberry, C.L., Nelson, C.D.S., and Maginnis, M.S. (2017). JC Polyomavirus Attachment and Entry: Potential Sites for PML Therapeutics. Current Clinical Microbiology Reports, 4(3):132-141.
• Dimitriadi M, Derdowski A, Kalloo G, Maginnis MS, O’Hern P, Bliska B, Sorkaç A, Nguyen KC, Cook SJ, Poulogiannis G, Atwood WJ, Hall DH, Hart AC. (2016). Decreased function of survival motor neuron protein impairs endocytic pathways. Proc Natl Acad Sci U S A. 2016 Jul 26;113(30):E4377-86.
• Luisa J. Ströh*, Maginnis, M.S.*, Bärbel S. Blaum, Christian D.S. Nelson, Ursula Neu, Gretchen V. Gee, Bethany A. O’Hara, Nasim Motamedi, Dan DiMaio, Walter J. Atwood, and Thilo Stehle. (2015). Increased affinity of JC Polyomavirus capsid for LSTc over other sialylated glycans is a major determinant of infectivity. Journal of Virology, 89(12):6364-75. *, Denotes co-first authors.
• Maginnis, M.S., Nelson, C.D.S., and Atwood, W.J. (2015). JC Polyomavirus Attachment, Entry, and Trafficking: Unlocking the Keys to a Fatal Infection. Journal of Neurovirology. J Neurovirol, 21(6):601-13. Read Abstract 
• Maginnis, M.S., Ströh, L.J., Gee, G.V., O’Hara, B.A., Derdowski, A., Stehle, T., and Atwood, W.J. (2013). PML-associated Mutations in the JC Polyomavirus Capsid Disrupt LSTc Binding. mBio, 4(3) e00247-13. Read Abstract
• Neu, U.*, Maginnis, M.S.*, Palma, A.S., Ströh, L.J., Nelson, C.D., Feizi, T., Atwood, W.J., and Stehle, T. (2010). Structure-Function Analysis of the Human JC Polyomavirus Establishes the LSTc Pentasaccharide as a Functional Receptor Motif. Cell Host & Microbe, 8(4):309-19. [Feature Article, Cover Illustration]. *, Denotes equal contribution. Read Abstract
• Maginnis, M.S., Haley S.A., Gee, G.V., and Atwood, W.J. (2010). Role of N-linked Glycosylation of the 5-HT2A Receptor in JC Virus Infection. Journal of Virology, 84(19):9677-84. Read Abstract

Grants