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Jody Rosenblatt

Assistant Professor of Oncological Sciences

B.A. University of California, Berkeley

Ph.D. University of California, San Francisco

Research

References

jody.rosenblatt@hci.utah.edu

Jody Rosenblatt's Lab Page

Jody Rosenblatt's PubMed Literature Search

Research

For normal tissue homeostasis, cells within a tissue maintain constant numbers by matching cell death with cell division. The epithelium is one of the largest tissues in the body and is continuously undergoing cell renewal. We study how cells within the epithelium turnover since misregulation of homeostasis is at the heart of epithelial tumor (carcinoma) formation.

EPITHELIAL APOPTOSIS—DEATH BY EXTRUSION: Most organs are coated with a protective layer of cells called epithelia. Yet, billions of cells in the epithelium die every hour in an adult. Given so much death, how does the epithelium maintain its primary function as a barrier? We found that before a cell dies, it relays a message to its neighbouring cells, which in turn, squeeze the dying cell out of epithelial layer, thereby preserving the layer’s barrier. To do this, the neighboring cells form a ring of actin and myosin around the apoptotic cell which contracts circumferentially and downwards to squeeze the cell out of the layer.

POLARITY OF EXTRUSION: We have found that while most cells extrude apically, into the lumen or outside of a tissue or organism, some cells can extrude basally, back into the tissue. We have recently found that microtubules play an important role in determining the direction a cell extrudes. To extrude apically, the microtubules in the neighboring cells reorient towards the basalateral surface to target Rho to assemble and contract actin and myosin IIA to squeeze the cell upwards. Further work will examine other factors that impinge on this cytoskeletal localization such as polarity genes and matrix.

EXTRUSION SIGNALING—A LINK WITH METASTASIS?: We found that while death signals induce both apoptosis and extrusion, these two processes can be separated. We are currently dissecting this pathway further and identifying the lipid signal on the outside of the dying cell that signals actin/myosin ring assembly for extrusion. Because extrusion can still occur in situations where cell death is blocked, extrusion could provide a mechanism for any cell to delaminate from the epithelium, as during development prior to differentiation of neuroblasts, for example. In tumors where cell death is blocked, extrusion could readily enable tumor cells to exit their primary sites and migrate to other sites. Because surprisingly little is known about how tumors initiate metastasis, we are investigating if extrusion may be a common mechanism. To do this, we are blocking cell death but not extrusion in zebrafish, where movement of individual cells can be clearly imaged live.

 

References