Thomas AE Platts-Mills, MD
Platts-Mills Lab and Willson Lab
Core team members in Dr. Thomas A.E. Platts-Mills’ lab include Jeffrey Wilson, MD, PhD, Core team members include Dr. Thomas A.E. Platts-Mills, Dr. Jeffrey Wilson, Behnam Keshavarz, PhD and Lisa Workman, BA. Working as a team, a major area of research relates to the tick-acquired mammalian meat allergy, often referred to as the ‘α-Gal syndrome’. Since the initial description of the syndrome a little over 10 years ago, the lab has continued to play an important role in increasing our understanding of the pathophysiology and manifestations of the syndrome. Current interests relate to emerging evidence that IgE sensitization to the relevant carbohydrate allergen – galactose-α-1,3-galactose (α-Gal) – could have implications for disorders that are not traditionally considered to be ‘allergic diseases’. To pursue the hypothesis that α-Gal could be relevant to heart disease we are collaborating with Coleen McNamara, MD and Angela Taylor, MD, MPH in cardiology, Robert Hawkins, MD in Cardiothoracic surgery, and also Ani Manichaikul, PhD in the School of Public Health Sciences. A major new interest relates to the possibility that α-Gal could be an important cause of IBS-like symptoms among subjects who live in areas where the lone star tick is endemic. To better understand risk factors for α-Gal sensitization we are collaborating with Cade Nylund, PhD at the Uniformed Services University of the Health Sciences in DoD-funded research to assess sensitization incidence among military recruits. We are also working closely with Phil Cooper, PhD to study α-Gal sensitization in a cohort of children in rural Ecuador who live in an area that is largely still pre-industrial. The group also has ongoing interests in the nature of antibody responses to common food and aero-allergens, such as cow’s milk and dust mite, with a specific focus on how these responses differ among different populations. Striking differences that are seen between children living in pre-and post-industrial societies likely have implications for thinking about the factors that have contributed to the rise of allergic diseases. The group has several recent publications and is currently funded by an NIH R-37 and R-21 grant. In addition, Dr. Wilson was recently awarded an AAAAI Faculty Development Award for work related to the α-Gal syndrome. Following receipt of the UVA Manning COVID-19 Research Fund, the team began work to develop an assay to measure antibodies to SARS-CoV-2. Taking advantage of the assay, they have described in quantitative terms the magnitude of antibodies to SARS-CoV-2 that developed in individuals who were naturally infected. This work was made possible by the efforts of several investigators at UVA who mobilized to study COVID-19, including Drs. Alexandra Kadl and Judith Woodfolk. Work is ongoing to measure antibody levels in individuals who have received COVID-19 vaccines. This has been made possible by the efforts of Dr. Nathan Richards, who has facilitated the recruitment of over 200 UVA employees into the vaccine cohort since January 2021.
Larry Borish, MD
Borish Lab
Dr. Larry Borish’s laboratory’s primary focus remains the role of rhinovirus in precipitating asthma exacerbations. These NIH-funded studies include a UO1 designed to define the role of an innate immune response, including anti-viral and T2-promoting immune responses, by infected airway epithelial cells as they might distinguish the consequences of RV infections in asthmatics and healthy control subjects. These studies are further supported by an R21 that investigates evidence for nascent type 2 inflammation in the lungs of pre-school children with problematic wheeze undergoing clinically indicated bronchoscopies in whom rhinovirus (RV) infection is identified. Also, for the next 2½ yrs, the Borish laboratory will be the co-lead sponsor of a Regeneron-funded investigator-initiated study entitled “Viral infection in asthma (VIA) Study: A randomized, placebo-controlled study to assess cellular and molecular markers related to experimental rhinovirus infection in mild asthmatics, and the effect of dupilumab in this investigational model.” The goal of this study will be to assess the molecular and cellular basis by which dupilumab prevents the development of an RV-induced asthma exacerbation. Unrelated to the RV studies, the Borish lab collaborates closely with Dr. Gerry Teague in pediatrics as co-PI for the UVA commitment to the NHLBI funded PreCISE Asthma Network Clinical Centers. These are studies that will enroll severe treatment-resistant asthmatics and investigate novel therapeutics in this refractory population. Finally, we also have several investigator-initiated pharmaceutical studies. Currently, we are enrolling patients in a GSK sponsored study to investigate type 2 inflammation in COPD and, more specifically the expression of IL-5 receptor on airway neutrophils. And, lastly, we are supported by a Regeneron funded investigator-initiated award involving the role of dupilumab in attenuated staphylococcus aureus infection in chronic sinusitis and amelioration of the dysbiotic state.
Judith Woolfolk, MD
Woodfolk Lab
The Woodfolk lab studies adaptive immunity to respiratory viruses in man and how this goes awry in patients with chronic respiratory diseases. Our inter-disciplinary team involves partnerships with physician-scientists across the Department and a diverse group of collaborators inside and outside UVA. The Woodfolk lab uses high-dimensional immuno-phenotyping methods and novel computational tools to monitor the immune response to rhinovirus (RV) in a human experimental infection model (NIH U01 project). This novel model involves challenging healthy individuals with two different RV strains to better understand how adaptive response components link to cross-protective immunity. Work in another RV infection model planned for later this year will test how type 2 cytokine blockade influences the immune response to RV in patients with asthma. The analytical pipelines developed in RV infection models have allowed our team to pivot rapidly to work on SARS-CoV-2/COVID-19. Ongoing initiatives in this area include: (1) Monitoring the evolution of T cell responses to SARS-CoV-2 in recovered patients to identify biomarkers of post-acute pulmonary complications (collaboration with Drs. Catherine Bonham, Alexandra Kadl, Mike Shim, Jeffrey Sturek, Jeffrey Wilson, and Behnam Keshavarz); and (2) Defining the protective features of T cell immunity in vaccinated individuals. A novel aspect is the incorporation of MHCII/peptide tetramers to track rare virus-specific CD4+ T cells in the blood and tissues. We hope that our work will inform the rational design of vaccines and provide tools for immune monitoring in broader disease settings.
Emily McGowan, MD
McGowan Lab
Dr. McGowan’s group continues to expand their research on an emerging form of food allergy, eosinophilic esophagitis (EoE). Through her NIH/NIAID K23 Award, Dr. McGowan established the UVA EoE Cohort with her collaborators Drs. Bryan Sauer (Adult Gastroenterology) and Barrett Barnes (Pediatric Gastroenterology). This cohort longitudinally follows approximately 300 patients, and it was designed to examine the environmental, nutritional, and immunologic drivers of this disease. In addition, Dr. McGowan recently received a NIH/NIAID R21 Award to examine non-IgE mediated activation of mast cells via food-derived peptides and the role of this pathway in EoE. In a recently funded American College of Gastroenterology award, she and her fellow PI, Dr. Bryan Sauer, are working to understand better the role of dietary triggers in the pathogenesis of EoE. Her group is also collaborating with Dr. Irving Allen (Virginia Tech School of Veterinary Medicine), through a recently funded iTHRIV pilot grant (NIH/NCATS) to investigate the role of the non-canonical NF-kB pathway in the pathogenesis of this disease. Finally, UVA is now a site for the international, multi-center Phase III trial of Dupilumab in treating Eosinophilic Esophagitis (R668-EE-1774).
Monica Lawrence, MD
Lawrence Lab
Dr. Monica Lawrence continues to work with Dr. W. Gerry Teague in Pediatrics and Dr. Larry Borish to understand the airway inflammatory milieu of children with severe treatment-refractory asthma. Along with Dr. Borish, she is also researching the role of a low IgE as a sentinel biomarker for evolving humoral immunodeficiency (research sponsored by the Jeffrey Modell Foundation and CSL Behring).
Anna Smith, MD
Smith Lab
Dr. Anna Smith along with Dr. Michael Nelson is leading the UVA study site for a national NIH/NIAID sponsored study of allergic reactions to the mRNA COVID-19 vaccines. The purpose of the SARS Vaccination study is to investigate if people with a history of serious allergic reactions or those with mast cell disorders are more at risk of having a reaction after receiving either the Pfizer-BioNTech COVID-19 Vaccine or the Moderna COVID-19 Vaccine and what factors may promote allergic reactions to either vaccine to include measurements of biomarkers. This study is now open for enrollment for people ages 18-69 years old with a history of serious allergic reactions or a mast cell disorder, or a history of no allergies at all.
Filed Under: Basic Research, Education
Tags: Allergy, DOM, Grants, May 2021, May 2021 Medicine Matters, May 2021 Newsletter, medicine matters, Research