Bio


Susan E. Vleck is a Senior Biosafety & Biosecurity Specialist and Manager of the Animal Research Occupational Health & Safety Program in the Department of Environmental Health & Safety at Stanford University. She earned her B.A. in Biology with Honors from Grinnell College in 2004, and her Ph.D. in Microbiology and Immunology at Stanford University in 2010. Her Ph.D. research centered on viral pathogenesis relating to functional and structural domains of Varicella-Zoster virus glycoproteins, and her Post-Doctoral research focused on investigating Hepatitis C virus and antiviral drugs, utilizing a humanized-liver mouse model. She now applies her background in viral microbiology to aiding Stanford researchers working with recombinant DNA and biohazardous agents. She supports the ongoing development and implementation of Stanford's Biosafety & Biosecurity Program and ensures safe practices, understanding, and compliance for work done using infectious biohazardous agents and recombinant DNA. Her research support role includes reviewing protocols and training associated with research overseen by the Administrative Panel on Biosafety, as well as acting as a voting member or administrator of the panel, as needed. Her research compliance role involves providing biosafety-related resources and oversight for the Administrative Panel on Biosafety, the Administrative Panel on Laboratory Animal Care and the Institutional Review Board Stem Cell Research Oversight panel. In these capacities, she works with Stanford’s research community of faculty, staff, post-doctoral scholars and grad students, other groups within Environmental Health & Safety, other departments at Stanford, and local, state and federal institutions that provide regulatory or guidance documentation. She currently lives in Santa Clara, CA, with her husband and two children, and likes to run and scuba dive in her spare time.

Current Role at Stanford


Current Role: Senior Biosafety & Biosecurity Specialist, and Manager, Animal Research Occupational Health & Safety Program

I have been a part of the Biosafety & Biosecurity group within the Department of Environmental Health and Safety at Stanford University since 2012. I support the ongoing development and implementation of Stanford's Biosafety & Biosecurity Program and ensure safe practices, understanding, and compliance for work done using infectious agents and recombinant DNA.

In my research support role, I aid Stanford Faculty, Staff, Post-doctoral Researchers, Grad Students and Undergraduates by conducting on-site "Biovisits", reviewing Administrative Panel on Biosafety (APB) approved projects, addressing training needs and research protocol safety deficiencies, acting as an APB voting member or administrator as needed, recommending and implementing ABSL2 trainings, and managing the APB online protocol site for updates and maintenance.

In my research compliance role, I act as the Biosafety resource and provide oversight for the Administrative Panel on Laboratory Animal Care (APLAC/IACUC) and Institutional Review Board (IRB) Stem Cell Research Oversight Panel (SCRO), coordinate approvals among APB and APLAC, SCRO and IRB, and review protocols requiring EH&S approval for submission to specific institutions. I also focus on updating Biosafety-related materials or trainings and implementing changes according to regulatory and guidance material as supplied by local, state and federal agencies.

I oversee the Animal Research Occupational Health & Safety Program, which serves a centralized point of contact for people seeking help relating to animal and EH&S issues. This program helps bring together groups within EH&S, as well as EH&S and other Stanford departments, to address safety and health issues relating to animals. These issues can fall under a wide range of topics, including biosafety, chemical safety, ergonomics, occupational injury & illness, trainings, lab safety, radiation safety, housing requirements, animal allergies, lasers and PPE. This program serves the research community, but also any staff, student or faculty who interacts with or works in proximity to animals on campus.

My overall goal in my role as a Biosafety & Biosecurity Specialist is to support the Stanford research community in performing innovative and exciting research safely.

Supervisors


Honors & Awards


  • Molecular Basis of Host-Parasite Interactions Training Grant, Stanford University (2008-2009)
  • Katherine McCormick Travel Award, Stanford University (2007)
  • National Science Foundation Graduate Research Fellowship Honorable Mention, NSF (2005)
  • Cell and Molecular Biology Training Grant, Stanford University (2004-2008)
  • Florence Smith-Sifferd Science Scholarship, Grinnell College (2002-2004)
  • Grinnell National Merit Scholarship, Grinnell College (2000-2004)
  • Grinnell Trustee Honors Scholarship, Grinnell College (2000-2004)

Education & Certifications


  • RBP, American Biological Safety Association, Registered Biosafety Professional (2017)
  • Post-Doctoral Scholar, Stanford University, Gastroenterology and Hepatology (2012)
  • Ph.D., Stanford University, Microbiology and Immunology (2010)
  • B.A., Grinnell College, Biology, with Honors (2004)

Personal Interests


Science: viruses, genetics, fusion proteins, glycoproteins
Life: running, scuba diving (PADI Master Scuba Diver, PADI Divemaster), road biking

Professional Affiliations and Activities


  • Member, American Biological Safety Association (2012 - Present)
  • Divemaster, Professional Association of Dive Instructors (PADI) (2010 - Present)
  • Member, American Society of Microbiology (2007 - Present)

All Publications


  • Safety Considerations When Working with Humanized Animals. ILAR journal Villano, J. S., Vleck, S. E., Felt, S. A., Myers, D. D., Lester, P. A. 2018

    Abstract

    Research using laboratory animals has been revolutionized by the creation of humanized animal models, which are immunodeficient animals engrafted with human cells, tissues, or organs. These animal models provide the research community a unique and promising opportunity to mimic a wide variety of disease conditions in humans, from infectious disease to cancer. A vast majority of these models are humanized mice like those injected with human CD34+ hematopoietic stem cells and patient-derived xenografts. With this technology comes the need for the animal research enterprise to understand the inherent and potential risks, such as exposure to bloodborne pathogens, associated with the model development and research applications. Here, we review existing humanized animal models and provide recommendations for their safe use based on regulatory framework and literature. A risk assessment program-from handling the human material to its administration to animals and animal housing-is a necessary initial step in mitigating risks associated with the use of humanized animals in research. Ultimately, establishing institutional policies and guidelines to ensure personnel safety is a legal and ethical responsibility of the research institution as part of the occupational health and safety program and overall animal care and use program.

    View details for PubMedID 30541024

  • Analogs design, synthesis and biological evaluation of peptidomimetics with potential anti-HCV activity BIOORGANIC & MEDICINAL CHEMISTRY Lasheen, D. S., Ismail, M. A., Abou El Ella, D. A., Ismail, N. S., Eid, S., Vleck, S., Glenn, J. S., Watts, A. G., Abouzid, K. A. 2013; 21 (10): 2742-2755

    Abstract

    Two series of peptidomimetics were designed, prepared and evaluated for their anti-HCV activity. One series possesses a C-terminal carboxylate functionality. In the other series, the electrophilic vinyl sulfonate moiety was introduced as a novel class of HCV NS3/4A protease inhibitors. In vitro based studies were then performed to evaluate the efficacies of the inhibitors using Human hepatoma cells, with the vinyl sulfonate ester (10) in particular, found to have highly potent anti-HCV activity with an EC(50) = 0.296 μM. Finally, molecular modeling studies were performed through docking of the synthesized compounds in the HCV NS3/4A protease active site to assess their binding modes with the enzyme and gain further insight into their structure-activity relationships.

    View details for DOI 10.1016/j.bmc.2013.03.017

    View details for Web of Science ID 000318318700011

    View details for PubMedID 23583031

  • Structure-function analysis of varicella-zoster virus glycoprotein H identifies domain-specific roles for fusion and skin tropism PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Vleck, S. E., Oliver, S. L., Brady, J. J., Blau, H. M., Rajamani, J., Sommer, M. H., Arvin, A. M. 2011; 108 (45): 18412-18417

    Abstract

    Enveloped viruses require membrane fusion for cell entry and replication. For herpesviruses, this event is governed by the multiprotein core complex of conserved glycoproteins (g)B and gH/gL. The recent crystal structures of gH/gL from herpes simplex virus 2, pseudorabies virus, and Epstein-Barr virus revealed distinct domains that, surprisingly, do not resemble known viral fusogens. Varicella-zoster virus (VZV) causes chicken pox and shingles. VZV is an α-herpesvirus closely related to herpes simplex virus 2, enabling prediction of the VZV gH structure by homology modeling. We have defined specific roles for each gH domain in VZV replication and pathogenesis using structure-based site-directed mutagenesis of gH. The distal tip of domain (D)I was important for skin tropism, entry, and fusion. DII helices and a conserved disulfide bond were essential for gH structure and VZV replication. An essential (724)CXXC(727) motif was critical for DIII structural stability and membrane fusion. This assignment of domain-dependent mechanisms to VZV gH links elements of the glycoprotein structure to function in herpesvirus replication and virulence.

    View details for DOI 10.1073/pnas.1111333108

    View details for Web of Science ID 000296700000053

    View details for PubMedID 22025718

    View details for PubMedCentralID PMC3215059

  • Structural Linkage between Ligand Discrimination and Receptor Activation by Type I Interferons CELL Thomas, C., Moraga, I., Levin, D., Krutzik, P. O., Podoplelova, Y., Trejo, A., Lee, C., Yarden, G., Vleck, S. E., Glenn, J. S., Nolan, G. P., Piehler, J., Schreiber, G., Garcia, K. C. 2011; 146 (4): 621-632

    Abstract

    Type I Interferons (IFNs) are important cytokines for innate immunity against viruses and cancer. Sixteen human type I IFN variants signal through the same cell-surface receptors, IFNAR1 and IFNAR2, yet they can evoke markedly different physiological effects. The crystal structures of two human type I IFN ternary signaling complexes containing IFNα2 and IFNω reveal recognition modes and heterotrimeric architectures that are unique among the cytokine receptor superfamily but conserved between different type I IFNs. Receptor-ligand cross-reactivity is enabled by conserved receptor-ligand "anchor points" interspersed among ligand-specific interactions that "tune" the relative IFN-binding affinities, in an apparent extracellular "ligand proofreading" mechanism that modulates biological activity. Functional differences between IFNs are linked to their respective receptor recognition chemistries, in concert with a ligand-induced conformational change in IFNAR1, that collectively control signal initiation and complex stability, ultimately regulating differential STAT phosphorylation profiles, receptor internalization rates, and downstream gene expression patterns.

    View details for DOI 10.1016/j.cell.2011.06.048

    View details for PubMedID 21854986

  • Structure-function Profiles of Nine Varicella-Zoster Virus Glycoproteins: Endocytosis, Entry And Egress Alphaherpesviruses: Molecular Virology Grose, C., Vleck, S., Karlsen, O., Montalvo, E. A. Caister Academic Press. 2011
  • Structure-Function Profiles of Nine Varicella-zoster Virus Glycoproteins: Endocytosis, Entry and Egress ALPHAHERPESVIRUSES: MOLECULAR VIROLOGY Grose, C., Vleck, S., Karlsen, O., Montalvo, E. A., Weller, S. K. 2011: 153–74
  • Varicella-Zoster Virus T Cell Tropism and the Pathogenesis of Skin Infection VARICELLA-ZOSTER VIRUS Arvin, A. M., Moffat, J. F., Sommer, M., Oliver, S., Che, X., Vleck, S., Zerboni, L., Ku, C. 2010; 342: 189-209

    Abstract

    Varicella-zoster virus (VZV) is a medically important human alphaherpesvirus that causes varicella and zoster. VZV initiates primary infection by inoculation of the respiratory mucosa. In the course of primary infection, VZV establishes a life-long persistence in sensory ganglia; VZV reactivation from latency may result in zoster in healthy and immunocompromised patients. The VZV genome has at least 70 known or predicted open reading frames (ORFs), but understanding how these gene products function in virulence is difficult because VZV is a highly human-specific pathogen. We have addressed this obstacle by investigating VZV infection of human tissue xenografts in the severe combined immunodeficiency mouse model. In studies relevant to the pathogenesis of primary VZV infection, we have examined VZV infection of human T cell (thymus/liver) and skin xenografts. This work supports a new paradigm for VZV pathogenesis in which VZV T cell tropism provides a mechanism for delivering the virus to skin. We have also shown that VZV-infected T cells transfer VZV to neurons in sensory ganglia. The construction of infectious VZV recombinants that have deletions or targeted mutations of viral genes or their promoters and the evaluation of VZV mutants in T cell and skin xenografts has revealed determinants of VZV virulence that are important for T cell and skin tropism in vivo.

    View details for DOI 10.1007/82_2010_29

    View details for Web of Science ID 000282104800012

    View details for PubMedID 20397071

  • Anti-Glycoprotein H Antibody Impairs the Pathogenicity of Varicella-Zoster Virus in Skin Xenografts in the SCID Mouse Model JOURNAL OF VIROLOGY Vleck, S. E., Oliver, S. L., Reichelt, M., Rajamani, J., Zerboni, L., Jones, C., Zehnder, J., Grose, C., Arvin, A. M. 2010; 84 (1): 141-152

    Abstract

    Varicella-zoster virus (VZV) infection is usually mild in healthy individuals but can cause severe disease in immunocompromised patients. Prophylaxis with varicella-zoster immunoglobulin can reduce the severity of VZV if given shortly after exposure. Glycoprotein H (gH) is a highly conserved herpesvirus protein with functions in virus entry and cell-cell spread and is a target of neutralizing antibodies. The anti-gH monoclonal antibody (MAb) 206 neutralizes VZV in vitro. To determine the requirement for gH in VZV pathogenesis in vivo, MAb 206 was administered to SCID mice with human skin xenografts inoculated with VZV. Anti-gH antibody given at 6 h postinfection significantly reduced the frequency of skin xenograft infection by 42%. Virus titers, genome copies, and lesion size were decreased in xenografts that became infected. In contrast, administering anti-gH antibody at 4 days postinfection suppressed VZV replication but did not reduce the frequency of infection. The neutralizing anti-gH MAb 206 blocked virus entry, cell fusion, or both in skin in vivo. In vitro, MAb 206 bound to plasma membranes and to surface virus particles. Antibody was internalized into vacuoles within infected cells, associated with intracellular virus particles, and colocalized with markers for early endosomes and multivesicular bodies but not the trans-Golgi network. MAb 206 blocked spread, altered intracellular trafficking of gH, and bound to surface VZV particles, which might facilitate their uptake and targeting for degradation. As a consequence, antibody interference with gH function would likely prevent or significantly reduce VZV replication in skin during primary or recurrent infection.

    View details for DOI 10.1128/JVI.01338-09

    View details for Web of Science ID 000272564300013

    View details for PubMedID 19828615

    View details for PubMedCentralID PMC2798403

  • Intramolecular and intermolecular uridylylation by poliovirus RNA-dependent RNA polymerase JOURNAL OF VIROLOGY Richards, O. C., Spagnolo, J. F., Lyle, J. M., Vleck, S. E., Kuchta, R. D., Kirkegaard, K. 2006; 80 (15): 7405-7415

    Abstract

    The 22-amino-acid protein VPg can be uridylylated in solution by purified poliovirus 3D polymerase in a template-dependent reaction thought to mimic primer formation during RNA amplification in infected cells. In the cell, the template used for the reaction is a hairpin RNA termed 2C-cre and, possibly, the poly(A) at the 3' end of the viral genome. Here, we identify several additional substrates for uridylylation by poliovirus 3D polymerase. In the presence of a 15-nucleotide (nt) RNA template, the poliovirus polymerase uridylylates other polymerase molecules in an intermolecular reaction that occurs in a single step, as judged by the chirality of the resulting phosphodiester linkage. Phosphate chirality experiments also showed that VPg uridylylation can occur by a single step; therefore, there is no obligatory uridylylated intermediate in the formation of uridylylated VPg. Other poliovirus proteins that could be uridylylated by 3D polymerase in solution were viral 3CD and 3AB proteins. Strong effects of both RNA and protein ligands on the efficiency and the specificity of the uridylylation reaction were observed: uridylylation of 3D polymerase and 3CD protein was stimulated by the addition of viral protein 3AB, and, when the template was poly(A) instead of the 15-nt RNA, the uridylylation of 3D polymerase itself became intramolecular instead of intermolecular. Finally, an antiuridine antibody identified uridylylated viral 3D polymerase and 3CD protein, as well as a 65- to 70-kDa host protein, in lysates of virus-infected human cells.

    View details for DOI 10.1128/JVI.02533-05

    View details for Web of Science ID 000239189100013

    View details for PubMedID 16840321

    View details for PubMedCentralID PMC1563691

  • Rapid communication: Physical and linkage mapping of the porcine calcitonin (CALC) gene JOURNAL OF ANIMAL SCIENCE Neil, J. E., Vleck, S. E., Helm, J. M., Ciobanu, D. C., Rothschild, M. F. 2002; 80 (6): 1700-1701

    View details for Web of Science ID 000176161600037

    View details for PubMedID 12078754