Clinical/Research Interests
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.
