Areas of Research: Immunopathogenesis of chronic sinusitis, biomarkers for determining outcome in chronic sinusitis, evidence-based medicine, clinical outcomes, clinical trials.
I am a clinician-scientist whose research interests are to understand the molecular and immunopathologic changes found in chronic rhinosinusitis (CRS) and their impact on clinical outcomes with the ultimate long term goal of finding novel means to treat patients with this disease. CRS is a chronic and debilitating inflammatory condition of the nose and paranasal sinuses that affects millions of adults. Since there is little known about the pathobiology of this common disease, my research, in conjunction with the Northwestern University Sinus and Allergy Center, takes a multi-pronged approach.
Understanding B-cell and antibody responses in CRS
In the subtype of CRS associated with nasal polyp formation (CRSwNP), there is extensive activation of B-cells and their consequent antibody responses. This is driven by molecular factors including the over-expression of related chemokines and cytokines such as BAFF (Kato et al., JACI 2008). Evidence for dysregulation of their antibody responses can be found in the production of locally and in some instances systemically elevated levels of self-reactive autoantibodies (Tan et al, JACI 2011; Jeffe et al, Laryngoscope 2013; van Roey et al, JACI 2017; Min et al, JACI 2017). Our NIH funded research focuses on understanding the specificities of these autoantibodies, the clinical implications of self-reactive antibodies in the nose, airway and circulation and studying their potential to serve as biomarkers for more aggressive, treatment resistant varieties of CRS.
Understanding the molecular mechanisms of Type 2 inflammation
CRS is among the most common causes of reversible smell loss in patients but yet about half the patients do not reliably regain their sense of smell following treatment. The mechanism by which this smell loss occurs is yet unknown but appears to be a combination of conductive effects and direct damage to the olfactory region. We have found that Type 2 inflammation characterized by eosinophils, and the cytokines IL-5 and IL-13 are the strongest predictors of smell loss in patients with CRS (Thompson et al, IFAR 2016; Lavin et al, Laryngoscope et al, JACI 2017). Our NIH funded laboratory focuses on understanding the mechanisms by which Type 2 inflammation causes epithelial and olfactory neuroepithelial damage and pharmacologic strategies to reverse these changes.
Measuring the effects of CRS at the population level
Since CRS significantly impairs quality of life, we are interested in developing and identifying instruments that will enable us to measure the impact of CRS in a longitudinal manner. We have completed an NIH funded epidemiologic study of the pre-morbid disease associations of CRS (Tan et al, JACI 2013), health utility (Ference et al AJRA 2018) and population symptom burden of this condition (Hirsch, Allergy 2015, 2017). We now further seek to develop a molecular understanding of the biological underpinnings of these quality of life impairments.