My research centers on biochemical mechanisms of immunology, specifically eosinophilic disorders. Pediatric Eosinophilic Esophagitis (EE) is an emerging disease characterized by anelevated eosinophil population in the esophagus leading to severe esophageal remodeling and inflammation. This results in intolerance towards eating; often eating is so painful that sensory disruption results in a violent refusal towards food. Malnourishment, vomiting, diarrhea and general failure to thrive are typical presentations of pediatric EE patients. Because of a superficial presentation resembling the more common gastroesophageal reflux disease (GERD), patients with EE are often misdiagnosed. They are, however, nresponsive to GERD treatment and one diagnostic feature of EE is the failure to resolve even at high dose administration of proton pump inhibitors. Although EE has only been appreciated as a distinct disorder for a relatively short time, great strides are being made in the understanding of this disorder.
Recent studies have established an association of EE with TH2 allergic responses, and food allergies are theorized to be a major participating factor. In addition, an EE-specific esophageal profile of transcribed mRNA and miRNA (the EE transcriptome) has been elucidated with the cytokine interleukin-13 (IL-13) playing an important role in the generation of the EE transcriptome. While much of the current research in this area is focused on the pathways of disease initiation, I am investigating mechanisms of esophageal remodeling.
I am fortunate to be part of a collaborative effort with the Cincinnati Center for Eosinophilic Disorders (CCED) at Cincinnati Children’s Hospital which allows me access to transgenic EE mouse models and a large databank of human esophageal biopsy samples. We have recently presented initial analysis of the pediatric EE transcriptome and have identified several genes involved in the remodeling process, including several matrix metalloproteinases (MMP) and lysyl oxidases (LOX).
Presently, we are attempting to elucidate the role of these proteins in esophageal remodeling using the IL-13 transgenic mouse model. We have identified several MMP and LOX isozymes that are differentially regulated in the transgenic mouse model and we are exploring their role in the progression of esophageal remodeling. The goal of our research is to understand esophageal remodeling in eosinophilic esophagitis so that treatment plans targeting remodeling can be designed. This could potentially alleviate a painful component of this disorder and also to minimize esophageal damage that occurs during the early treatment stages of pediatric EE.
I am also in the initial stages of exploration on a project aimed at determining the role osteopathic manipulation in gene expression of GERD patients. It has long been suspected that manipulative medicine may be effective for treatment of GERD, however no biochemical basis has ever been established. While I have access to willing osteopathic physicians who are eager to participate in this project, our patient population in eastern Kentucky is simply not sufficiently large or centralized enough to pursue this project in this area. A larger, centralized population would be necessary to allow this type of project. While this project is still in the planning stages, I believe it could rapidly be developed and would be an opportunity for clinical and basic science faculty to collaborate.
In addition to my research interests, I am also active in community-based initiatives focusing on nutrition and supplementation. While I have given presentations to many types of community groups, I specifically target high school and college athletic teams. With these presentations, I am attempting to inform the audience of the basic functions of dietary components and how they relate to exercise, athletic performance, and in some cases, weight management.
A secondary goal is to provide athletes with basic information regarding common supplements in order to make them aware of the costs, effectiveness (or lack thereof), and potential dangers of many OTC supplements. I receive no compensation for these presentations; however I find value in educating young athletes on topics they would otherwise receive information only from popular media.