Current Projects
The aim of Tetsuo Shoda, MD's research program focuses on severe allergies (e.g., eosinophilic gastrointestinal disease), specifically:
- studying their pathogenesis
- optimizing the diagnosis and monitoring of these allergies
- contributing to personalized medicine to treat these allergies
Currently, the Shoda Lab is working on profiling and endotyping eosinophilic gastrointestinal disease and its molecular and genetic contributors.
Molecular Diagnostic Panels, Blood Biomarkers, Disease Endotypes and Mechanisms for Eosinophilic Gastrointestinal Disorders
Though eosinophilic esophagitis (EoE) research has greatly advanced in recent years, there still remains unexplored patient populations and an unmet need for more precise diagnostic tools for all eosinophilic gastrointestinal disorders (EGID), especially non-EoE EGID.
A central goal for our research in the Shoda Lab is to identify the transcriptomes of EGID and apply them for molecular diagnosis and biomarkers, which has been made possible with the advent of new diagnostic technology, such as RNA sequencing and multiplex panels.
In addition to the gene expression profiles, we have worked to identify blood biomarkers to assess non-EoE EGID, such as eosinophilic gastritis (EoG), eosinophilic duodenitis (EoD), and eosinophilic colitis (EoC). Through local collaborations with the Rothenberg CURED Lab and national collaborations with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), we identify distinct transcriptomes in non-EoE EGID and develop tissue- and blood-based platforms for assessing non-EoE EGID.
For EoG, we have uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease. The EoG platforms have already been adopted by a leading national consortium focused on EGID (CEGIR); for example, by being applied to clinical trials (such as NCT03320369).
Combinatory Effects of Genetic Variants in Eosinophilic Esophagitis
Eosinophilic esophagitis (EoE) is an allergic disease of the esophagus and has a complex, genetic basis. Though recent research progress suggests that EoE is linked to genetic variants, testing single variants separately does not consider how these variants may be interacting nor how these interactions may bring about or impact disease.
This project will evaluate how EoE-linked variants interact and what effects these interactions have on disease features. As part of the project, our lab will develop risk scores based on involved biological pathways to predict the chance of developing EoE.
This work is supported by an NIAID grant, titled “Combinatory Effects of Genetic Variants in Eosinophilic Esophagitis” (K99/R00 AI158660, PI Shoda, 07/01/2021-06/30/2025).
Characterizing the Effects of Genes/Variants Using Ex Vivo Disease Modeling Systems
Disease models that recapitulate the relevant pathology in humans support the importance of genes / variants in disease etiology.
In addition to utilizing patient-derived biopsies, the Shoda Lab uses cutting-edge 3D in vitro gastrointestinal organoid culture systems (esophagus, stomach, intestine, and colon) from human induced pluripotent stem cells (iPSCs) with genome editing by CRISPR-Cas9, allowing rapid linking of genetic data to quantifiable phenotypic information for personalized genetic evaluation.