Judith A. Woodfolk, MD, PhD

PRIMARY APPOINTMENT:

Professor of Medicine

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).

External Collaborations:

Dr. Jonathan Irish – Vanderbilt University, Nashville, TN.

Dr. William Kwok – Benaroya Research Institute, Seattle, WA.

Dr. Anna Pomes – Indoor Biotechnologies Inc., Charlottesville, VA.

CURRENT LABORATORY MEMBERS

Judith Woodfolk, Glenda Candera, Lyndsey Muehling, Paul Dell, and Naomi Bryant

Glenda Canderan, PhD Lyndsey Muehling, PhD Naomi Bryant, MS Paul Dell

SELECTED PUBLICATIONS

Keshavarz B, Wiencek JR. Workman LJ, Straesser MD, Muehling LM, Canderan G, Drago F, Bonham CA, Sturek JM, Ramani C, McNamara CA, Woodfolk JA, Kadl A, Platts-Mills TA, Wilson JM. Quantitative measurement of IgG to severe acute respiratory syndrome coronavirus-2 proteins using ImmunoCAP. Int Arch Allergy Immunol. 2021;182:417-24.
Barone SM* Paul AG*, Muehling LM*, Lannigan JA, Kwok WW, Turner RB, Woodfolk JA, Irish JM^§. Unsupervised machine learning reveals key immune cell subsets in COVID-19, rhinovirus infection, and cancer therapy. BioRxiv. 2020. Aug 1:2020.07.31.190454.
Muehling LM, Heymann PW, Wright PW, Eccles JD, Agrawal R, Carper HT, Murphy DD, Workman LJ, Word CR, Ratcliffe SJ, Capaldo BJ, Platts-Mills TA, Turner RB, Kwok WW, Woodfolk JA. Human Th1 and Th2 cells targeting rhinovirus and allergen coordinately promote allergic asthma. J Allergy Clin Immunol. 2020;146:555-570.
Heymann PW, Platts-Mills TA, Woodfolk JA, Borish L, Murphy DD, Carper HT, Conaway MR, Steinke JW, Muehling L, Gerald TW, Kennedy JL, Irani AM, McGraw MD, Early SV, Wheatley LM, Adams AP, Turner RB. Understanding the asthmatic response to an experimental rhinovirus infection: Exploring the effects of blocking IgE. J Allergy Clin Immunol. 2020;146:545-554.
Eccles JD, Turner RB, Kirk NA, Muehling LM, Borish L, Steinke JW, Payne SC, Wright PW, Thacker D, Lahtinen SJ, Lehtinen MJ, Heymann PW, Woodfolk JA. T-bet+ memory B cells link to local cross-reactive IgG upon human rhinovirus infection. Cell Rep. 2020;30:351-66.
Glesner J, Kapingidza AB, Godzwon M, Offermann LR, Mueller GA, DeRose EF, Wright P, Richardson CM, Woodfolk JA, Vailes LD, Wünschmann S, London RE, Chapman MD, Ohlin M, Chruszcz M, Pomés A. A Human IgE antibody binding site on Der p 2 for the design of a recombinant allergen for immunotherapy. J Immunol. 2019;203:2545-56.
Muehling LM, Turner RB, Brown KB, Wright PW, Patrie JT, Lahtinen SJ, Lehtinen MJ, Kwok WW, Woodfolk JA. Single-cell tracking reveals a role for pre-existing CCR5+ memory Th1 cells in the control of rhinovirus-A39 after experimental challenge in humans. J Infect Dis. 2018; 217:381-92.
Wisniewski JA*, Muehling LM*, Eccles JD, Capaldo BJ, Agrawal R, Shirley DA, Patrie JT, Workman LJ, Schuyler AJ, Lawrence MG, Teague WG, Woodfolk JA. Th1 signatures are present in the lower airways of children with severe asthma regardless of allergic status. J Allergy Clin Immunol. 2018; 141:2048-60.
Muehling LM, Lawrence MG, Woodfolk JA. Pathogenic CD4+ T cells in patients with asthma. J Allergy Clin Immunol. 2017;140:1523-40. [Review].
Muehling LM, Mai DT, Kwok WW, Heymann PW, Pomés A, Woodfolk JA. Circulating Memory CD4+ T cells target conserved epitopes of rhinovirus capsid proteins and respond rapidly to experimental infection in humans. J Immunol. 2016;197:3214-24.