Function of the intestine and how progenitor cell relationships change during GI disease processies like cancer and inflammatory damage.
A large focus of my work is on the normal function of the intestine and how progenitor cell relationships change during GI disease processies like cancer and inflammatory damage. Relevant to this basic research area, I am the director of the cell development subcore of the DDRC. In this core we develop new normal, conditionally immortalized, mouse epithelial cell lines from various mouse models and human tissue. These cell lines have been made for members of the Vanderbilt Community as well as for other labs around the country and world.
A major focus of my work concerns the function of cell secreted vesicles called exosomes. In ongoing studies we have found that EGFR ligands are in exosomes represent a new and unique way to activate EGFR that influences tumor cell growth and metastasis in a different way than other ligand presentation mechanisms. An integral area of my research concerns the role that non-coding RNAs (miRNAs and long-non-coding) have in influencing stem cell and altered neoplastic signals. We have seen that ncRNAs can act to regulate growth of normal intestinal cells and when overexpressed can lead to invasive cancers by regulating miRNA function. We have found that exosomes carry numerous miRNAs, mRNAs and long non-coding RNAs and their trafficking to exosomes is regulated by mutant oncogenic KRAS. This area of research has the potential to increase our understanding of how tumors affect their microenvironment, how they may signal to the metastatic niche and also hold great promise for biomarker research.
We are also interested in the genes that control intestinal stem cell growth and differentiation and how abnormal signaling in CRC is associated with alterations in stem cell gene function, including modulators of EGFR function. These include negative regulators of EGFR as well as Wnt signaling components, as there is crosstalk between EGFR and Wnt signaling. Other areas of research include a collaboration between our lab and GE to use the GE MultiOmyxâ„¢ system to perform microscopic imaging of individual tissue sections with fluorescence microscopy, using up to 100 antibody stains for each individual section. Antibody staining of individual cells in multiple images is all registered allowing single cell analysis that provides an expression landscape within an in situ tissue microenvironment.