Cell Differentiation

PI -Michael Papetti, PhD, Research Assistant Professor, Pharmaceutical and Biomedical Sciences

Our research investigates how cells are programmed to adopt a normal state of differentiation and how this programming is disrupted in cancer. One of the major model systems we use is the maturation of epithelial cells along the crypt-luminal axis of the colon. Ordered migration of colon epithelial cells from the bottom to the top of the crypt is required for their differentiation. Because aberrant colon cell migration may contribute to early stages of colon tumorigenesis, elucidation of how this migration is regulated provides insight into how colon cancer can be prevented and treated before malignancy. Certain actin-binding tropomyosins, including tropomyosin 4 (TPM4), regulate cytoskeletal contractility and migration in many different cell types. Our data suggests that aberrantly upregulated TPM4 may be an early event in colon tumorigenesis and that normal TPM4 expression, by fostering ordered colon epithelial cell migration, may promote normal cell differentiation and mitigate adoption of a premalignant state.

Another focus of our studies utilizes video microscopy to reveal many aspects of epithelial cell biology that are not possible by staticimaging alone. We have constructed a simple, low-cost (<$500) apparatus that maintains a microscope and cell culture vessel at 37 +/-0.4 degrees Celsius for extended time periods. Using this instrument, we have observed several phenomena in colon epithelial tumor cells, including novel membrane fusion events and aberrant cell divisions, that elucidate many physiological mechanisms utilized by these cells in normal as well as disease states. This apparatus is currently being used to visualize and measure responses, particularly in terms of absorption and migration, of colon epithelial cells to vitamin D treatment, and to visualize individual protein localization by incorporating fluorescence microscopy of GFP-labeled proteins.

Papetti, M. and Kozlowski,P., “Novel Aspects of Live Intestinal Epithelial Cell Function Revealed Using a Custom Time-Lapse Video Microscopy (TLVM) Apparatus”, Cytometry A93:464-471(2018)