Dr. Mulligan’s laboratory focuses on understanding the mechanisms that initiate and exacerbate inflammatory diseases of the upper and lower airways with a significant emphasis on chronic rhinosinusitis (CRS). CRS affects up to 16% of the US population with direct costs of nearly $22 billion per year. Its negative impact on quality of life exceeds other chronic conditions, such as heart failure and chronic obstructive pulmonary disease. Furthermore, CRS is highly prevalent in severe asthmatics and is associated with a greater frequency of exacerbations. Our laboratory works closely with clinicians and scientists spanning multiple disciplines allowing us to conduct cutting edge translational research using human tissue and rodent models. The majority of our research falls into four main areas:
- Vitamin D: Given vitamin D’s ability to promote anti-viral and anti-microbial immune responses, while simultaneously preventing an overreaction of the immune system, it is well suited as a therapeutic target for a number of airway diseases. Our laboratory focuses on how oral vitamin D supplementation, local airway vitamin D metabolism, and local delivery of active vitamin D may all play roles in respiratory health.
- Airway Epithelial cell dysfunction: One cell population identified as a therapeutic target, for a number of airway diseases, are respiratory epithelial cells. Environmental insults including; fungi, bacteria, viruses, and allergens, as well as topically delivered therapeutic agents interact initially with epithelial cells in the respiratory tract. In patients with CRS and/or asthma, epithelial cells have altered functions including cytokine/chemokine production and are hyper-responsive to antigen stimulation. What remains unclear and is a focus of our investigations, is to identify a means by which to reduce their intrinsically pro-inflammatory nature.
- Olfactory loss: Sinusitis is the most common cause of temporary and permanent olfactory loss, and in CRS with nasal polyps, up to 50% of patients suffer from anosmia even after medical or surgical treatment. Our research group had identified a number of factors in humans related to CRS and non-CRS olfactory loss. Many of these factors could be targeted with intranasal delivery of existing drugs approved for other diseases, which is a focus of our ongoing investigations.
- Nasal mucus biomarkers: Our laboratory was the first to establish a standardized method from the collection of nasal mucus and demonstrate its utility as a surrogate for tissue biopsies to study immunological changes in the upper airway. Nasal mucus biomarker research has now evolved into an invaluable research tool that has revolutionized the research of upper airway inflammation. So much so that in the recent report “Clinical Research Needs for the Management of Chronic Rhinosinusitis with Nasal Polyps in the New Era of Biologics. A National Institute of Allergy and Infectious Diseases Workshop” nasal mucus biomarkers were highlighted as playing a critical role in clinical trials for the first biological treatments for CRS in the US. Through partnerships across UF and the US, we are investigating how nasal mucus immune signatures can be used to identify novel therapies for the treatment of CRS.