Research Overview

The Overbaugh lab studies the viral and immune determinants of infectious diseases, with a focus on HIV and SARS-CoV-2 infections.  We leverage natural history studies to focus our work on studying these determinants in  settings most relevant to human disease.

Studies of Innate Immunity

What are the key antiviral host genes that regulate virus replication?
What is the role of NK cells in HIV pathogenesis?

Diagram showing expansion and persistence of HIV-specific natural killer cell populations following HIV infection.

Discovery of antiviral host genes in CD4+ T cells

  • Developed CRISPR screening methods in primary T cells for HIV
  • Developed screens for ZIKV antiviral host genes
CRISPR screening workflow in CD4+ T cells used to identify interferon-induced genes that inhibit HIV replication.

Top hit for CXCR4 virus has opposing effects on X4 and R5 variants

Bar chart showing top candidate host genes identified in an HIV antiviral gene screen, led by SLC35A2.
Scatter plot comparing results from two gene screens, highlighting a candidate antiviral interferon-stimulated gene.
Illustration of the HIV virus showing its structural components.
Itell et al., Cell Reports 2023 Itell et al., Nature Microbiology, 2024
Illustration of the Zika virus particle.
Willcox et al., PNAS 2025
Natural killer cell targeting and killing an HIV-infected CD4+ T cell.

Studies of NK memory responses to HIV

  • Identification of HIV-specific NK cell clones in response to HIV infection
Diagram showing expansion and persistence of HIV-specific natural killer cell populations following HIV infection.

Studies of adaptive immunity: HIV and SARS-CoV-2

Nab discovery and analysis

  • HIV
  • SARS-CoV-2
HIV infected infant diagram
Simonich et al. Cell Reports Medicine 2021
Diagram characterizing broadly neutralizing antibody responses
Simonich et al. Cell 2016
epitope profiling
Dingens et al., Cell Host and Microbe, 2017 Dingens et al., Immunity, 2019
SARS-CoV-2 antibodies
SARS-CoV-2 antibodies Guenthoer et al., PNAS 2023 Ruiz et al., PLoS Pathogens 2024 Lilly et al, mBio 2026

ADCC Functionality of Protective Antibodies

  • HIV
  • SARS-CoV-2
diagram of breastfeeding hiv exposure
Yaffe and Naiman et al., Cell Reports Medicine 2021
SARS-CoV-2 antibodies
SARS-CoV-2 antibodies Depierreux et al., PLoS Pathogens, 2026
human immunodeficiency virus (HIV) and its major components.
Human immunodeficiency virus (HIV) Yaffe and Naiman et al Cell Reports Medicine 2021

Mutations

Mutations contributing to Nab and ADCC function
mutations contributing to nab and adcc function
Simonich and Doepker et al., Nature Communications 2019
SARS-CoV-2 antibodies
SARS-CoV-2 antibodies Guenthoer et al., in prep, 2026
human immunodeficiency virus (HIV) and its major components.
Human immunodeficiency virus (HIV) Simonich et al., Nature Communications 2019 Shipley et al., eLife 2021 Doepker et al., eLife 2021