Susan E. Vleck is Assistant Director, Laboratory Chemical and Physical Safety, and Manager, 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 scientific research to aiding Stanford researchers in incorporating safety into their everyday work. She leads the ongoing development and implementation of Stanford's Laboratory Chemical and Physical Safety Program, and ensures safe practices, understanding, and compliance for work done in a wide array of research labs. She leads and directs a team of 8 management and professional personnel to oversee a broad spectrum of environmental, health and safety programs of significant scope and complexity, and oversees subordinate managers with large program responsibilities. She defines and directs the overall activities of the group, and allocates appropriate staffing and other resources to achieve objectives, including development and direction of related policies. 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: Assistant Director, Laboratory Chemical and Physical Safety Program., and Manager, Animal Research Occupational Health and Safety Program, Department of Environmental Health and Safety
I have been a part of the Department of Environmental Health and Safety at Stanford University since 2012. My original role was as a Biosafety and Biosecurity Specialist to support the ongoing development and implementation of Stanford's Biosafety and Biosecurity Program and ensure safe practices, understanding, and compliance for work done using infectious agents and recombinant DNA. I was promoted to Senior Biosafety and Biosecurity Specialist in 2017, and became Program Manager for the Animal Research Occupational Health and Safety Program. In 2020, I transitioned to my current role of Assistant Director, Laboratory Chemical and Physical Safety Program.
I lead the ongoing development and implementation of Stanford's Laboratory Chemical and Physical Safety Program, and ensure safe practices, understanding, and compliance for work done in a wide array of research labs. I lead and direct a team of 8 management and professional personnel to oversee a broad spectrum of environmental, health and safety programs of significant scope and complexity, and oversee subordinate managers with large program responsibilities. I define and direct the overall activities of the group, and allocate appropriate staffing and other resources to achieve objectives, including development and direction of related policies.
I also directly 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 Assistant Director is to support the Stanford research community in performing innovative and exciting research safely.
Honors & Awards
Stanford Staff Academy, Stanford University (2016)
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)
Science: viruses, genetics, fusion proteins, glycoproteins
Life: running, scuba diving (PADI Master Scuba Diver, PADI Divemaster), road biking
Professional Affiliations and Activities
Member, Stanford University Emergency Operations Center (EOC) for COVID-19 (2020 - Present)
Associate Chair, Research Operations Continuity Committee, Stanford University EOC COVID-19 (2020 - Present)
Member, Academic Policy Group, Stanford University EOC COVID-19 (2020 - Present)
Member, Labs, Libraries and Shared Facilities Policy Working Group, Stanford University EOC COVID-19 (2020 - Present)
Member, Front Range Biosafety Association (FRaBSA) (2020 - Present)
Member, Scientific Program Committee, ABSA (2020 - Present)
Member, Laboratory Acquired Infections database, Publications Committee, ABSA (2019 - Present)
Member, Midwest Area Biosafety Network (MABioN) (2018 - Present)
Member, Northern California Biosafety Association (NorCal) (2018 - Present)
Member, American Biological Safety Association (ABSA) (2013 - Present)
Member, Campus Safety, Health and Environmental Management Association (CSHEMA) (2012 - Present)
Divemaster, Professional Association of Dive Instructors (PADI) (2010 - Present)
Member, American Society of Microbiology (2007 - Present)
- Safety Considerations When Working with Humanized Animals ILAR JOURNAL 2018; 59 (2): 150–60
Analogs design, synthesis and biological evaluation of peptidomimetics with potential anti-HCV activity
BIOORGANIC & MEDICINAL CHEMISTRY
2013; 21 (10): 2742-2755
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
2011; 108 (45): 18412-18417
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
2011; 146 (4): 621-632
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
View details for Web of Science ID 000287717200009
Anti-Glycoprotein H Antibody Impairs the Pathogenicity of Varicella-Zoster Virus in Skin Xenografts in the SCID Mouse Model
JOURNAL OF VIROLOGY
2010; 84 (1): 141-152
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
Varicella-Zoster Virus T Cell Tropism and the Pathogenesis of Skin Infection
2010; 342: 189-209
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
Intramolecular and intermolecular uridylylation by poliovirus RNA-dependent RNA polymerase
JOURNAL OF VIROLOGY
2006; 80 (15): 7405-7415
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 2002; 80 (6): 1700-1701