About

Cynthia A. Derdeyn, PhD, is a Professor and Vice Chair of Research in the Department of Laboratory Medicine and Pathology at the University of Washington. Her research combines studies of human subjects and animal models to develop and evaluate novel approaches for vaccination against HIV and elimination of the viral reservoir. Her focus is on viral diversity, particularly within the highly variable envelope glycoproteins, and the B cell and antibody responses that are elicited during infection and vaccination. She has held academic appointments at Emory University, where she served as Professor and previously as Associate Professor, and has a background in biochemistry and molecular genetics from Georgia State University. Her research interests include HIV/AIDS, immunology, vaccines, B cells, and antibody responses.

Research topics

• Biology
• Virology
• Immunology
• Chemistry
• Molecular biology
• Medicine

Selected publications

• Poldip2 deficiency attenuates lung disease severity in a mouse model of COVID-19

  PLoS ONE · 2026-04-29

  articleOpen access

  The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the infection resulting in lung inflammation, pulmonary vascular leakage and diffuse alveolar damage. Polymerase delta-interacting protein-2 (Poldip2) mediates lung inflammation and vascular permeability after lipopolysaccharide-induced acute respiratory distress syndrome; however, whether it also affects the pathological consequences of SARS-CoV-2 infection is completely unknown. Here, we assessed the role of Poldip2 in inflammation, immune cell infiltration and lung tissue damage in response to SARS-CoV-2. Our data show that Poldip2 expression was elevated in human lung vascular endothelium after infection. In a Poldip2-deficient heterozygous mouse model, acute clinical symptoms were not affected. However, seven days after infection, Poldip2 knockdown reduced viral load, decreased infiltration of myeloperoxidase (MPO)-positive neutrophils into inflamed lungs, and reduced tissue damage. Poldip2 also modulated the inflammatory response to viral infection in a heterogeneous manner, reflecting its diverse regulatory roles. These data support the concept that targeting Poldip2 could potentially attenuate severe lung injury following SARS-CoV-2 infection.

  PublisherDOI

• <p>Endothelial Poldip2 is upregulated in human lung after SARS-CoV-2 infection.</p>

  Figshare · 2026-04-29

  otherOpen access

  Sections of lung tissue were immunostained for CD31 (green), Poldip2 (red) and nuclei (blue). Left: representative images from one control and one infected patient. Right: quantification of Poldip2 staining in CD31-positive areas. Numbers below the bars correspond to individual patients. Bars represent means ± SEM from 4-10 pictures per sample taken at random locations. Data were analyzed using a two-tailed nested Student t-test, n = 3, *P < 0.05.

  PublisherDOI

• <p>Image segmentation to measure alveolar septal thickness.</p>

  Figshare · 2026-04-29

  otherOpen access

  Lungs from male and female hACE2/Poldip2 mice were processed and stained with H&E. Example of a 500 x 500 µm tile extracted from a whole slide image (Left). Corresponding binary mask generated by the morphometry Fiji plugin, showing successful segmentation prior to measurement of septal thickness (Right). Additional details can be found under Methods and in the original publication [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0348065#pone.0348065.ref026" target="_blank">26</a>]. (TIF)

  PublisherDOI

• Structure of HIV-1 Env glycoprotein on virions reveals an alternative fusion subunit organization and native membrane coupling

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-10 · 4 citations

  articleOpen access

  An effective vaccine for Human Immunodeficiency Virus type-1 (HIV-1) has yet to be developed, and detailed characterization of functional Env glycoprotein, the primary antigenic target on virions, has remained elusive. While engineered Env trimers recapitulate many aspects of functional Env, key differences in antigenicity and dynamic behavior have been reported. Here, cryo-electron tomography and subtomogram averaging of HIV-1 virus-like particles (VLPs) revealed conformational differences in critical membrane-proximal regions compared to soluble Envs. Hydrogen/Deuterium-Exchange Mass Spectrometry and Molecular Dynamics captured dynamic profiles of membrane-bound Env and identified critical interactions with membrane. We show that disruption of the viral membrane results in relaxation of Env to a form that resembles engineered, soluble trimers. Additionally, Env from mature and immature VLPs exhibit only minor conformational differences, while surface clustering on virions changes significantly. These studies provide new insights into the essential role the membrane plays in maintaining Env in its native conformational form.

  PublisherOA PDFDOI

• <p>Acute infection does not significantly reduce body weights and temperatures.</p>

  Figshare · 2026-04-29

  otherOpen access

  Male and female human ACE2 transgenic, Poldip2^+/+ or Poldip2^+/- (hACE2/Poldip2) mice received a single intranasal inoculation of PBS or SARS-CoV-2 on day zero. Body temperatures (A, B) and weights (C, D) were measured every other day. Time courses (A, C) show relative values, calculated by dividing measurements for each mouse by its own initial value (day zero) and multiplied by 100 for weights. The graphs represent means ± SEM of data from n = 8-21 animals. Body temperatures at day 6 (B) and weight changes between day 6 and day zero (D), were analyzed by 2-way ANOVA: ns, not significant. On day zero, average body temperatures were identical between males and females, across all groups (35 ± 0.1°C) and average body weights were higher by a few grams in males (M) than females (F): M 29.4 ± 0.7, F 21.6 ± 0.4 in Poldip2 + /+ and M 25.9 ± 0.5, F 21.4 ± 0.3 in Poldip2 + /- (errors indicate SEM).

  PublisherDOI

• Population-level genomic analysis of immunoglobulin loci variation in rhesus macaques reveals extensive germline diversity

  Immunity · 2026-01-01

  articleOpen access

  Rhesus macaques (RMs) are a vital model for studying human disease and are invaluable to preclinical vaccine research, particularly for the study of broadly neutralizing antibody responses. Such studies require robust genetic resources for antibody-encoding genes within the immunoglobulin (IG) loci. The complexity of the IG loci has historically made them challenging to characterize accurately. To address this, we developed experimental and computational methodologies to generate a collection of integrated antibody repertoire and long-read genomic sequencing data in 106 Indian-origin RMs. We created a resource of IG heavy- and light-chain variable (V), diversity (D), and joining (J) alleles, as well as leader, intronic, and recombination signal sequences (RSSs). This includes the curation of 1,095 previously unidentified alleles, unveiling tremendous diversity and expanding existing IG allele sets by 40%. This publicly available, continually updated resource (https://vdjbase.org/reference_book/Rhesus_Macaque) provides the foundation for advancing RM immunogenomics, vaccine discovery, and translational research.

  PublisherDOI

• <p>Primer and probe sequences.</p>

  Figshare · 2026-04-29

  datasetOpen access

  <div> The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the infection resulting in lung inflammation, pulmonary vascular leakage and diffuse alveolar damage. Polymerase delta-interacting protein-2 (Poldip2) mediates lung inflammation and vascular permeability after lipopolysaccharide-induced acute respiratory distress syndrome; however, whether it also affects the pathological consequences of SARS-CoV-2 infection is completely unknown. Here, we assessed the role of Poldip2 in inflammation, immune cell infiltration and lung tissue damage in response to SARS-CoV-2. Our data show that Poldip2 expression was elevated in human lung vascular endothelium after infection. In a Poldip2-deficient heterozygous mouse model, acute clinical symptoms were not affected. However, seven days after infection, Poldip2 knockdown reduced viral load, decreased infiltration of myeloperoxidase (MPO)-positive neutrophils into inflamed lungs, and reduced tissue damage. Poldip2 also modulated the inflammatory response to viral infection in a heterogeneous manner, reflecting its diverse regulatory roles. These data support the concept that targeting Poldip2 could potentially attenuate severe lung injury following SARS-CoV-2 infection. </div>

  PublisherDOI

• <p>Numbers of male (M) and female (F) mice in experimental groups.</p>

  Figshare · 2026-04-29

  datasetOpen access

  Numbers of male (M) and female (F) mice in experimental groups.

  PublisherDOI

• Reconstructing a Missing Link of HIV-1 Assembly: HIV-1 Envelope-Matrix Interactions in a Native Viral Context

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-16 · 1 citations

  articleOpen access

  The envelope surface glycoprotein (Env) on HIV-1 drives cell entry and genome delivery through its receptor binding and membrane fusion activities. Incorporation of Env onto assembling virions is governed by its cytoplasmic tail (Env-CT) and the matrix (MA) domain of the PR55Gag (Gag) polyprotein. To better understand how Gag recruits Env onto virions while reducing its antigenic profile by restricting Env copy number to low levels, we used cryo-electron tomography (cryo-ET) and subtomogram averaging combined with molecular dynamics simulations to investigate Env-MA association in intact viral particles. Full-length Env-CT was resolved directly over individual MA trimers in regions of MA lattice discontinuity. We observed that the conserved but enigmatic Kennedy-sequence motif in Env-CT forms a key linkage between Env and MA. Mutational analysis confirmed the impact of specific CT and MA interactions on Env incorporation. Gag maturation released MA lattice restraints on Env, facilitating its clustering and promoting fusion activity.

  PublisherOA PDFDOI

• <p>Poldip2 depletion reduces viral load 7 days post-infection.</p>

  Figshare · 2026-04-29

  otherOpen access

  Male and female hACE2/Poldip2 mice were infected with SARS-CoV-2 by nasal inoculation. Lungs were collected 7 days later for RNA preparation. Viral loads were measured by RT-qPCR using primer pairs and TaqMan probes specific for the viral gene N (A) or subgenomic E (sgE) RNA (B). Bars represent means ± SEM of data from n = 5-7 animals. Groups were compared using two-tailed Mann-Whitney tests: **P < 0.01.

  PublisherDOI

Recent grants

• Using DNA/MVA/protein immunization of rhesus macaques to investigate how the background of the HIV-1 envelope and nature of the protein boost shape the genetic and functional antibody landscape.

  NIH · $5.9M · 2017–2023

• Role of Follicular T Helper Cells In Enhancing Humoral Immunity and Protection

  NIH · $20.4M · 2017

• Determinants of Neutralization Breadth in Early HIV-1 Infection

  NIH · $6.7M · 2004–2019

• NIH Grant P51RR000165

  NIH · $43.4M · 2016

• CD40L Adjuvanted Clade C DNA and MVA HIV Vaccines -Administrative Core

  NIH · $20.4M · 2020

Frequent coauthors

• Eric Hunter

  Rwanda Zambia HIV Research Group

  142 shared

• S. Abigail Smith

  HOPE Clinic

  61 shared

• George M. Shaw

  California University of Pennsylvania

  57 shared

• Joseph Mulenga

  48 shared

• Frédéric Bibollet‐Ruche

  University of Pennsylvania

  45 shared

• Susan Allen

  Rwanda Zambia HIV Research Group

  41 shared

• Beatrice H. Hahn

  University of Pennsylvania

  39 shared

• Julie M. Decker

  Alaska Fisheries Development Foundation

  39 shared

Education

• Ph.D., laboratory medicine, pathology

  University of Washington

• M.D.

  University of Washington

• Other

  University of Washington

• B.S.

  University of Washington