Research

            

            

            

Clinical/Translational Research

We are committed to increasing our pre-surgical armamentarium to combat the pervasive problems with inflammatory sinus disease, to make sinus surgery both less common overall, but also safer when performed. Rhinology is still in an emerging specialty when compared to other disciplines like cardiac and ophthalmologic surgery, which have a smorgasbord of medical and minimally-invasive procedural options available prior to surgery. In our practice, we routinely evaluate patients who have experienced a variety of avoidable and unavoidable complications from sinus surgery, which speaks to the need for improved medical options for sinus and allergy treatment, novel tools for minimally invasive sinus approaches (one of which we have designed and patented), improved surgical education, and realistic access to surgical simulation training.

            

            

Empty Nose Syndrome (ENS) and Upper Airway Physiology

Our lab focuses on disorders of nasal physiology and nasal breathing, particularly with regard to the debilitating disease termed empty nose syndrome (ENS). Our practice of >100 patients with ENS has allowed the design and validation of what are now considered gold standard subjective (ENS6Q) and provocative (nasal cotton test) tests to more accurately identify patients suffering from ENS.

Our validation study of the ENS6Q questionnaire was named the Best Clinical Research Paper at the American Rhinologic Society at the 2016 national meeting, and the cotton test validation received cover article honors. Through international patient assessment, we have also measured the functional and psychological burden presented by empty nose syndrome and have assessed how the nasal mucosa remodels in ENS patients over time compared to controls using imaging. We are currently assessing the benefit/impact of candidate treatments for ENS patients using subjective and objective outcome measures.

            

            

Immunology: Immune Systems and Immunity

The innate and adaptive immunologic microenvironment in chronic human upper airway diseases like chronic rhinosinusitis (CRS) has also been of ongoing interest of our group. We have shown altered levels of cytokines, oxidases, and Tregs in CRS patients and recently, through collaboration with Drs. Bruce Tan and Robert Schleimer at Northwestern University, IgD+ B cell populations that are selectively recruited into the chronically inflamed tissue beds within the upper airway. Our findings underscore numerous attractive opportunities to better understand immune dysregulation in the human upper airway.

            

            

Stem Cell / Regenerative Medicine for Upper Airway Diseases

Upper airway diseases of the nasal cavity and sinuses create significant morbidities and socioeconomic burdens. These include the many forms of chronic rhinosinusitis (CRS), which afflict 10% of the US population, the rare but debilitating breathing disorder termed empty nose syndrome (ENS, described under a different heading, and cystic fibrosis (CF), the #1 most lethal genetic disease in the world. diseases. 

We are using advanced cellular and molecular techniques, in murine and human systems, to better understand the mechanisms utilized by upper airway basal stem cells (ABCs) to maintain, repair and regenerate the upper airway epithelial barrier in both health and disease. is critical to improving available treatments for these common disease processes.  

Our laboratory has helped to pioneer early discoveries of mouse and human UABCs that are abundant, multipotent progenitors. We have studied ABCs using a variety of cell culture, flow cytometry, imaging, microarray and single cell molecular platforms to understand the biologic properties and unique signatures expressed by these cells.

We recently confirmed the direct involvement of ABCs in human upper airway tissue repair in patients undergoing sinus/skull base surgery. This was a randomized, blinded controlled trial undertaken at Stanford (Dr. Nayak and colleagues) and the University of Alabama Birmingham (Dr. Woodworth and colleagues), to understand whether use of a porcine tissue graft (termed pSIS) would promote/improve wound healing and tissue regeneration in the upper airway.  Our findings were that the pSIS significantly improved epithelial regeneration in the nasal airway, and that enhanced recruitment of ABCs into the wound healing tissue bed was present.  

Finally, we have advanced an exciting collaboration with 3 other laboratory groups at Stanford, to determine whether it is possible to efficiently perform genome correction of critical mutations that lead to cystic fibrosis at the stem cell level. With the Nayak lab group providing the human airway basal stem cells (ABCs) from cystic fibrosis and non-CF patients from surgery, the ABC stem cell numbers are then amplified in the organoid biology laboratory of Dr. Calvin Kuo, taken to the CRISPR gene editing laboratory of Dr. Matthew Porteus for CFTR mutational correction. After stem cell expansion and functional analysis/imaging in the laboratories of Drs. Tushar Desai and Zachary Sellers, the normalized/newly-corrected ABCs are returned to the Nayak Lab for cell embedding and transplantation experiments. The goal of this work is to design a novel, stem cell-based treatment for cystic fibrosis, and our advances to date are currently under review at the journal Cell Stem Cell. 

With our experimental foundation, we feel that airway basal stem cells represent a highly attractive cell therapy modality for treating a variety of upper (and possibly lower) airway disorders.