1) Human patient-derived organoids to study upper GI metaplasias and cancers. We have established a biobank of organoids from pre-cancerous metaplastic and neoplastic lesions from human patients.
We will utilize our organoids to develop novel models of upper GI metaplasia/cancer development including implantation and co-culture systems.
These will allow us to investigate the pathogenesis of how these metaplasias develop and progress to cancers as well as more translational work to improve diagnosis and treatment.
2) Developmental context of upper GI metaplasias. To better understand the molecular origins of these metaplasias, it is useful to conceptualize them in a developmental context. An overlapping set of transcription factors determines and maintains GI tract differentiation, and aberrant transcriptional programming is likely at the root of the development of upper GI metaplasias.
Mouse models of upper GI metaplasias. We have developed mouse models to recapitulate the aberrant transcriptional programming that becomes active with the development of upper GI metaplasias.
Novel multi-omic characterization of upper GI metaplasias and cancers including use of bulk/single-cell RNA sequencing, spatial proteomics/transcriptomics, and CUT&RUN analyses.