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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

RESEARCH:  Our lab studies cell extrusion, a process that epithelia use to remove excess or dying cells while maintaining a functional barrier.

EPITHELIAL APOPTOSIS—DEATH BY EXTRUSION: Epithelia coat and protect most organs. Yet, billions of cells in our epithelia die every hour. Given so much death, how does the epithelium maintain its primary function as a barrier? Before a cell dies, it sends a signal to its neighbouring cells, which in turn, form a ring of actin and myosin that contract to squeeze the dying cell out of the epithelium, thereby preserving its barrier.  We have recently found that this signal is sphingosine 1 phosphate (S1P).

POLARITY OF EXTRUSION:While most cells extrude apically into the lumen, some cells can extrude basally, back into the tissue the epithelium encases.  The direction a cell extrudes is important for its later, especially when live cells extrude. For instance, during development or cancer, basally extruded cells could differentiate or invade, whereas apical extrusion deletes these cells. We have recently found that microtubules and adenomatous polyposis coli (APC) control the direction a cell extrudes by targeting where actin/myosin contract to squeeze the cell upwards.   When either is disrupted, extrusion occurs predominantly basally (see figure below).

EXTRUSION, CANCER, & DEVELOPMENT  Cells that comprise the epithelium constantly turn over via cell division and death. To maintain homeostasis, the numbers of cells that divide must match those that die, yet what controls this balance is not well understood. If too many cells accumulate, epithelial cancers (or carcinomas) result, whereas too much death results in poor barrier function. Importantly, epithelia in vivo typically extrude live cells that eventually die, suggesting that extrusion drives cell death to control cell numbers during homeostasis. Further, experimentally overcrowding cells also induces extrusion of live cells, suggesting that physical constraints control cell numbers. Blocking extrusion in zebrafish can lead to accumulation of cell masses (see right). In tumors where cell death is blocked, extrusion could either suppress tumor formation (if cells are expelled apically) or enable tumor cells to exit their primary sites and migrate to other sites (if they are extruded basally). We are currently investigating these possibilities using both mouse and zebrafish models, where movement of individual cells can be clearly imaged live.

 

References