Bio

Honors & Awards


  • Stanford SIGF Bio-X Interdisciplinary Graduate Fellowship Award, Stanford University (2014-2017)
  • SPARK/Spectrum Innovation Accelerator Seed Grant Award in Therapeutics, Stanford University, SPARK Program (2014-2015)
  • NIAID Merit Award for achievements associated with research on 2009 H1N1 pandemic influenza virus, National Institutes of Allergy & Infectious Diseases (2009)
  • Research Fellowship Training Award, National Institutes of Health (2008-2010)
  • WELCH Chemistry Undergraduate Research Grant, The WELCH Foundation (2005-2006)
  • Honor Society Member, Alpha Sigma Lambda (2005-)

Membership Organizations


  • Microbiology & Immunology Department, M&I graduate student co-president
  • Alpha Sigma Lambda Honor Society, Member
  • Association for Women in Science, Member of mentoring program

Education & Certifications


  • Bachelor of Arts, St Edwards University, Philosophy (2006)
  • Bachelor of Science, St Edwards University, Biochemistry (2006)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


Many of the most difficult infectious diseases to treat are caused by RNA viruses, such as influenza, hepatitis B/C/D, rhinovirus, dengue, etc. The challenge to treatment is due in part to the high error rates of RNA virus replication, which give rise to large, genetically diverse populations. Confounding the issue, RNA viruses also possess a great adaptive capacity to mutate under drug or immune pressures, often rendering antiviral therapies ineffectual.

My research aims to overcome these concerns by combating viruses in a different way: by targeting the genomic RNA itself. Unlike proteins that frequently mutate, genomic viral RNA often contain highly conserved regions and structures (such as packaging, translation, or replication signals) that are genetically maintained and strictly preserved. Just as many antibiotics target RNA secondary structures within bacteria, our goal is to develop a completely new class of antivirals that will similarly target RNA structures within viral genomes. To pursue these objectives, my work necessitates an interdisciplinary approach. By combining molecular virology and genetic tools with biochemistry and emerging high-throughput RNA structure-probing technologies, we have uncovered new RNA structure-function relationships and are currently developing a novel influenza therapeutic for the clinic.

Lab Affiliations


Publications

All Publications


  • Reconstitution and Functional Analysis of a Full-Length Hepatitis C Virus NS5B Polymerase on a Supported Lipid Bilayer. ACS central science Cho, N., Pham, E. A., Hagey, R. J., Lévêque, V. J., Ma, H., Klumpp, K., Glenn, J. S. 2016; 2 (7): 456-466

    Abstract

    Therapeutic targeting of membrane-associated viral proteins is complicated by the challenge of investigating their enzymatic activities in the native membrane-bound state. To permit functional characterization of these proteins, we hypothesized that the supported lipid bilayer (SLB) can support in situ reconstitution of membrane-associated viral protein complexes. As proof-of-principle, we selected the hepatitis C virus (HCV) NS5B polymerase which is essential for HCV genome replication, and determined that the SLB platform enables functional reconstitution of membrane protein activity. Quartz crystal microbalance with dissipation (QCM-D) monitoring enabled label-free detection of full-length NS5B membrane association, its interaction with replicase subunits NS3, NS5A, and template RNA, and most importantly its RNA synthesis activity. This latter activity could be inhibited by the addition of candidate small molecule drugs. Collectively, our results demonstrate that the SLB platform can support functional studies of membrane-associated viral proteins engaged in critical biological activities.

    View details for DOI 10.1021/acscentsci.6b00112

    View details for PubMedID 27504492

  • The Natural History of Influenza Infection in the Severely Immunocompromised vs Nonimmunocompromised Hosts. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Memoli, M. J., Athota, R., Reed, S., Czajkowski, L., Bristol, T., Proudfoot, K., Hagey, R., Voell, J., Fiorentino, C., Ademposi, A., Shoham, S., Taubenberger, J. K. 2014; 58 (2): 214-24

    Abstract

    Introduction. Medical advances have led to an increase in the world's population of immunosuppressed individuals. The most severely immunocompromised patients are those who have been diagnosed with a hematologic malignancy, solid organ tumor, or who have other conditions that require immunosuppressive therapies and/or solid organ or stem cell transplants. Materials and methods. Medically attended patients with a positive clinical diagnosis of influenza were recruited prospectively and clinically evaluated. Nasal washes and serum were collected. Evaluation of viral shedding, nasal and serum cytokines, clinical illness, and clinical outcomes were performed to compare severely immunocompromised individuals to nonimmunocompromised individuals with influenza infection. Results. Immunocompromised patients with influenza had more severe disease/complications, longer viral shedding, and more antiviral resistance while demonstrating less clinical symptoms and signs on clinical assessment. Conclusions. Immunocompromised patients are at risk for more severe or complicated influenza induced disease, which may be difficult to prevent with existing vaccines and antiviral treatments. Specific issues to consider when managing a severely immunocompromised host include the development of asymptomatic shedding, multi-drug resistance during prolonged antiviral therapy, and the potential high risk of pulmonary involvement. Clinical trials registration, ClinicalTrials.gov identifier NCT00533182.

    View details for DOI 10.1093/cid/cit725

    View details for PubMedID 24186906

  • Multidrug-resistant 2009 Pandemic Influenza A Viruses Maintain Fitness and Transmissibility in Ferrets Multidrug-resistant 2009 Pandemic Influenza A Viruses Maintain Fitness and Transmissibility in Ferrets Memoli, M., Davis, A., Proudfoot, K., Chertow, D., Hagey (Hrabal), R. J., Bristol, T., Taubenberger, J. K. 2011; 203 (3)

    View details for DOI 10.1093/infdis/jiq067

  • The PB2-E627K Mutation Attentuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase The PB2-E627K Mutation Attentuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase Jagger, B. W., Memoli, M. J., Sheng, Z., Qi, L., Hagey (Hrabal), R. J., Allen, G. L., Dugan, V. G., Wang, R., Digard, P., Kash, J. C., Taubenberger, J. K. 2010; 1 (1)

    View details for DOI 10.1128/mBio.00067-10

  • Prior infection with classical swine H1N1 influenza viruses is associated with protective immunity to the 2009 pandemic H1N1 virus Prior infection with classical swine H1N1 influenza viruses is associated with protective immunity to the 2009 pandemic H1N1 virus Kash, J. C., Qi, L., Dugan, V. G., Jagger, B. W., Hagey (Hrabal), R. J., Memoli, M. J., Morens, D. M., Taubenberger, J. K. 2010; 4 (3): 121-127
  • Rapid Selection of Oseltamivir- and Peramivir-Resistant Pandemic H1N1 Virus during Therapy in 2 Immunocompromised Hosts Rapid Selection of Oseltamivir- and Peramivir-Resistant Pandemic H1N1 Virus during Therapy in 2 Immunocompromised Hosts Memoli, M., Hagey (Hrabal), R. J., Hassantoufighi, A., Eichelberger, M. C., Taubenberger, J. K. 2010; 50 (9): 1252-1255

    View details for DOI 10.1086/651605

  • Rapid Selection of a Transmissible Multidrug-Resistant Influenza A/H3N2 Virus in an Immunocompromised Host Rapid Selection of a Transmissible Multidrug-Resistant Influenza A/H3N2 Virus in an Immunocompromised Host Memoli, M. J., Hagey (Hrabal), R. J., Hassantoufighi, A., Jagger, B. W., Sheng, Z., Eichelberger, M. C., Taubenberger, J. K. 2010; 201 (9): 1397-1403

    View details for DOI 10.1086/651610