Judith A. Woodfolk, MD, PhD

PRIMARY APPOINTMENT:

Professor of Medicine
Co-Director, UVA Medical Scientist Training Program

CONTACT:

UVA Division of Asthma, Allergy, and Clinical Immunology
PO Box 801355
MR-4, 5061
Telephone: 434-924-1293 / 434-982-3958
Fax: 434-924-1251
Email: jaw4m@virginia.edu

RESEARCH AREAS:

Immunology, Microbiology, Molecular Biology, Translational Science

RESEARCH SUMMARY

Overview

The Woodfolk lab studies the immune response to respiratory viruses.

We use translational models to understand how immune cells respond to viruses in health and disease. We aim to identify biomarkers predicting severe outcomes in at-risk patients and identify new strategies to prevent virus-induced lung damage.

Infection with rhinovirus, the major cause of the common cold, typically runs a benign course. However, in patients with asthma, rhinovirus exposure triggers acute wheezing episodes that often require hospitalization. We have characterized T cells and B cells that define a protective response to rhinovirus and established a previously unrecognized role for type 1 immunity in promoting allergic asthma. The analytical pipelines developed for rhinovirus have since laid the groundwork for work on SARS-CoV-2, the causative agent of COVID-19.

CURRENT PROJECTS

Studying Hallmarks of Protective Immunity to Rhinovirus Infection. Infections caused by the more than 150 strains of rhinovirus that are endemic in the United States account for over half a billion cases of common cold annually. Despite this, there is no vaccine or proven treatment for rhinovirus infection. We recently identified CCR5+ T cells in the blood that can respond to multiple rhinovirus strains. We are using a human experimental model that involves sequential infections with two different rhinoviruses A strains to identify cellular and molecular elements of the adaptive response that mediate cross-protection against multiple rhinovirus strains. This includes the use of novel computational algorithms to analyze spectral flow cytometry datasets to pinpoint complex cell phenotypes in the blood that relate to infection outcomes. Our findings have the potential to create novel vaccines and strategies for the treatment of the common cold. Work is supported by NIH/NIAID.
Understanding the Role of Rhinovirus-Specific T Cells in Asthma. Infection with rhinovirus is a major trigger of acute wheezing episodes in patients with allergic asthma. Our recent data suggest that rhinovirus-specific Th1 cells can drive airway inflammation in asthma, even when no infection is present. We have developed high-throughput analytical pipelines for virus-specific T cells that allow us to probe the transcriptome for pro-inflammatory pathways operating in these cells. In a rhinovirus challenge model, we are testing the capacity for cytokine blockade to disrupt these pathways and to re-program the immune response to rhinovirus in asthma. Work is supported by NIH/NIAID and Regeneron Pharmaceuticals.
Defining Protective and Pathogenic Immune Responses in SARS-CoV-2/COVID-19. We are using high-dimensional immune profiling to understand the nature of the immune response to SARS-CoV-2 in health and disease. This includes developing novel tools to precisely characterize virus-specific T cells that respond to vaccines and defining how T cells contribute to lung damage in patients with post-COVID syndrome who fail to successfully recover from COVID-19 infection. These projects involve long-term immune monitoring of highly characterized Vaccine and Recovery Cohorts and extensive interactions with clinical experts in order to link immune findings to clinical outcomes.
Assessing the Immunomodulatory Potential of Hypoallergenic Molecular Variants. Sensitization to dust mite allergens is common, and these allergens are potent inducers of IgE antibodies. Recombinant allergens that display reduced IgE binding provide a safe alternative to current immunotherapies for allergic disease. Ongoing work seeks to test the T cell modulatory potential of such hypoallergenic molecules.

Precision Medicine: Our methods combine state-of-the-art single-cell technologies and analytical tools with clinical data to construct the landscape of immune activation and its evolution over time. Our analytical pipelines allow us to link specific immunophenotypes to clinical outcomes. Assessing the response in various scenarios may inform personalized approaches to therapy.

Examples include:

Assessing the influence of genetic factors, asthma severity, and other co-morbidities on the immune response to respiratory viruses and vaccines.
In a randomized controlled study, monitoring the response to type 2 cytokine blockade in patients with asthma.
Tracking the response to milk avoidance in patients with eosinophilic esophagitis (planned).