Phoebe Stewart received her undergraduate AB degree from Harvard University with a major in Biochemistry and her PhD degree from the University of Pennsylvania in Chemistry. She learned cryo-electron microscopy as a Helen Hay Whitney postdoctoral fellow at the Wistar Institute in Philadelphia and the European Molecular Biology Laboratory in Heidelberg, Germany. She served as a faculty member in the Department of Molecular and Medical Pharmacology at the University of California Los Angeles and in the Department of Molecular Physiology and Biophysics at Vanderbilt University, before joining the faculty at Case Western Reserve University. The focus of her research group is to apply cryo-electron microscopy to a variety of macromolecular complexes. Her lab has published cryoEM structures of viruses, virus/host factor complexes, virus-like particle−polymer conjugates, as well as soluble proteins and membrane proteins. Whenever possible her lab utilizes hybrid structural approaches, combining cryoEM data with information derived from X-ray crystallography, NMR, EPR, mass spectrometry, molecular dynamics flexible fitting, and de novo structure prediction methods. An ongoing project is to examine the structure of human adenovirus in complex with various host immune factors. The goals are to understand how the viral capsid interacts with multiple host factors and to design an oncolytic virus suitable for systemic delivery. Oncolytic virotherapy has the potential to improve clinical outcomes in patients who are not responding to other cancer therapies.
Our lab studies the structure of engineered adenovirus vectors and their complexes with immune molecules. More specifically we focus on understanding the molecular mechanisms underlying systemic inflammation and how targeted viral capsid mutations might alter host-pathogen interactions. We utilize cryo-electron microscopy (cryo-EM) single particle reconstruction and tomography, molecular dynamics and molecular modeling.
Wagner N, Shayakhmetov DM, Stewart PL. Structural model for factor X inhibition of IgM and complement-mediated neutralization of adenovirus. (2023) Viruses 15(6), 1343. PMCID: PMC10305487
Emerson CC, Stewart PL. Structure-Based Modeling of Complement C4 Mediated Neutralization of Adenovirus. (2021) Viruses, 13, 111. https://doi.org/10.3390/v13010111 PMCID: PMC7830055
Atasheva S, Emerson CC, Yao J, Young C, Stewart PL, Shayakhmetov DM. Systemic cancer therapy with engineered adenovirus that evades innate immunity. (2020) Science Translational Medicine, 12, 571, eabc6659. DOI: 10.1126/scitranslmed.abc6659 PMCID: PMC9195642
Gulati NM, Miyagi M, Wiens ME, Smith JG, Stewart PL. α-Defensin HD5 stabilizes human papillomavirus 16 capsid/core interactions. (2019) Pathogens and Immunity, DOI: 10.20411/pai.v4i2.314 PMCID: PMC6755940
Stewart PL. (2017) Cryo-electron microscopy and cryo-electron tomography of nanoparticles. WIREs Nanomedicine & Nanobiotechnology, 9:e1417. doi: 10.1002/wnan.1417 PMID: 27339510