The overarching research goals of our consortium are to identify the monogenic causes of COngenital Diarrhea and Enteropathy (CODE), characterize their clinical and pathophysiological features, and develop a clinical database and biorepository of disease-specific cells, tissues, and other primary patient materials.
We are establishing four interacting and unique resources for investigation and characterization of the epithelial- cell specific disorders that typify CODE disorders. This includes i) a comprehensive clinically annotated biorepository of the CODE disorders; ii) a histopathological atlas; iii) a set of disease-specific high-throughput screening assays for epithelial cell function; and iv) an overlapping set of high-content imaging and functional assays for evaluating patient-specific enteroids to develop disease-specific therapies.
We are also actively investigating the biology of both known as well as newly discovered disease-causing CODE genes through collaborative studies between the research groups in the consortium.
We are establishing a comprehensive patient registry to investigate the natural history of genotyped CODE patients. The long-term outcome for these children is diverse and depends on the underlying monogenic defect. The natural history of these disorders has never been systematically examined, and the literature typically provides single institution reports with one or a small case series. Therefore, we are constructing a comprehensive multi-institutional registry of carefully genotyped patients that will allow for identification of disease-causing mutations in both known genes and hitherto unsuspected genes. In conjunction with clinical data about CODE patients we are establishing a CODE BioRepository (COBR) that will foster further in-depth studies in this unique group of patients by investigators within and outside of the consortium. The acquisition of blood, gut biopsy, fibroblasts, serum, and stool samples will provide opportunities to perform additional studies including biomarker discovery, and other “Omics” investigations, including microbiome and metabolome analysis.
To inquire about accessing our Biorepository please see Accessing the Biorepository
To find out more about Biorepository protocols please contact us
Phenotyping of the small and large bowel biopsy specimens in CODE disorders can provide critical information about the status of brush border structure, transporters and channels in the apical membrane and the presence of specific epithelial and immune cell populations in the mucosa. Due to the small size of most paraffin embedded mucosal biopsy samples, it has been difficult to establish a complete immunohistological phenotype in CODE disorders. Recent advances have culminated in the ability to perform Multiplex Immunofluorescence (MxIF) staining on small tissue biopsies. MxIF allows staining of 30-60 immunostains on a single histological section using antibodies with directly conjugated fluorescent dyes. The CODE Tissue Atlas is a community resource built by the PediCODE Consortium. The goal of the Atlas is to provide histological data on CODE disorders. This includes immunofluorescent identification of intestinal cell types and key epithelial proteins by multiplex immunofluorescence (MxIF) of biopsies and patient-derived primary organoids as well as standard histological stains (H&E etc.).
To find out more about review and referral of CODE patient pathology please see our Pathology page
To find out more about the Biorepository please contact us
We are developing new resources for both the consortium and the wider community including: i) technology for medium / high-throughput assessment of epithelial biology commonly associated with CODE disorders; ii) adaptation of those technologies for functional screens of compound libraries (e.g., approved FDA drug and small molecule libraries); and iii) model organism and patient-derived enteroid-based assays for gene function discovery and secondary validation of putative therapeutic compounds. Examples include recently developed quantitative and high-throughput assays of endosome biology, membrane trafficking in polarized epithelial cells, quantitative enteroid functional assays and novel enteroid imaging methods.
To find out more about published tools /assays please see our Publications page.
For use of reagents, detailed methods, or assistance with assays or tools please contact us