Professor of Oncological Sciences
B.A. University of California, Berkeley
Ph.D. University of California, San Francisco
Jody Rosenblatt's Lab Page
Jody Rosenblatt's PubMed Literature Search
Molecular Biology Program
Apoptotic Cell Extrusion, Homeostasis, Epithelial Cells
Epithelial cells work collectively together to form tight barriers around the organs they encase, yet they divide and die at some of the highest rates in the body. Epithelial cell death and division must be tightly balanced in order to maintain constant cell numbers or the barrier they form would rapidly vanish or become riddled with tumors. How is this balance maintained? Mechanical tension inextricably links cell death and division, balancing the number of cells dividing with those dying. When epithelial cells are too sparse, stretch triggers some to divide. Alternatively, when epithelia become too crowded, some cells are extruded, which later die. Extrusion is a process my lab discovered where epithelia seamlessly squeeze out cells fated to die without disrupting the barrier. How do epithelial cells sense mechanical tension? Surprisingly, we found that both crowding-induced cell extrusion and stretch-induced cell division require the same stretch-activated calcium channel, Piezo1. By disrupting the signaling controlling these mechanisms, we find that they are essential for maintaining proper epithelial cell densities. Misregulation of extrusion leads to common yet untreatable diseases, ranging from cancer to asthma. Understanding the root causes of these diseases is revealing new approaches to treat these diseases, rather than merely manage their symptoms.
My lab is currently focusing on the following main goals:
- Examining mechanisms by which Piezo1 triggers both epithelial cell division and cell death via live cell extrusion, using biochemical and cell biology techniques.
- Asthma: we find that excessive crowding from bronchoconstriction causes excessive extrusion of the airway epithelial lining that destroys the barrier and causes inflammation. We are developing a treatment to block this inflammatory cycle using mice as a model system.
- We have discovered a new mechanism for how cancer cells can invade and initiate metastasis throughout the body by hijacking apical extrusion and instead causing basal extrusion. Following these cells in transparent zebrafish is uncovering more fascinating findings about how these cells make their way throughout the body and escape treatment. We hope revealing these mechanisms will give us new ways to treat metastatic disease.
- Gudipaty SA, Lindblom J, Loftus PD, Redd MJ, Edes K, Davey CF, Krishnegowda V, Rosenblatt J. Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature. 2017 Mar 2;543(7643):118-121. PubMed PMID: 28199303; PubMed Central PMCID: PMC5334365.
> Heisenberg, C.-P. (2017). "Cell biology: Stretched divisions." Nature543(7643): 43-44. Faculty of 1000. Also, covered in a Nature podcast.
- Eisenhoffer GT, Slattum G, Ruiz OE, Otsuna H, Bryan CD, Lopez J, Wagner DS, Bonkowsky JL, Chien CB, Dorsky RI, Rosenblatt J. A toolbox to study epidermal cell types in zebrafish. J Cell Sci. 2017 Jan 1;130(1):269-277. doi: 10.1242/jcs.184341. Epub 2016 May 5. PubMed PMID: 27149923.
- Gu Y, Jill Shea J, Slattum GM, Firpo MA, Alexander M, Mulvihill SJ, Golubovskaya VM, Rosenblatt J (2015) Defective apical extrusion signaling contributes to aggressive tumor hallmarks. (ELife. 2015 Jan 26;4:e04069).
- Slattum GM, Gu Y, and Rosenblatt J. Oncogenic K-Ras promotes basal extrusion of epithelial cells by degrading S1P through autophagy. Current Biology, 2014 Jan 6 2014;24(1):19-28.
>Highlighted in Science Stke.
- Eisenhoffer GT*, Loftus PD*, Yoshigi M, Otsuna H, Chien CB, Morcos PA, and Rosenblatt J. Overcrowding induces extrusion of live cells to control epithelial cell numbers. Nature, 2012 484(7395):546-9. PMID:22504183
>Highlighted in Cell, and reviewed in Cell, Nature Reviews Molecular and Cell Biology, Current Biology, and medecine-sciences
- Marshall T, Lloyd IE, Delalande JM, Nathke I, and Rosenblatt J. The tumor suppressor adenomatous polyposis coli controls the direction a cell extrudes from an epithelium. Biol. Cell 2011 Nov;22(21):3962-70. PMID:21900494
>Highlighted in Science Signaling, and the American Society for Cell Biology Newsletter and awarded winner of the 2012 MBoC Paper of the Year Award.
- Eisenhoffer GT and Rosenblatt J. Live imaging of cell extrusion from the epidermis of developing zebrafish. Journal of Visualized Experiments. 2011 Jun 27;(52). pii: 2689. doi: 10.3791/2689. PMID: 21730948
- Gu Y, Forostyan T, Sabbadini R, Rosenblatt J. Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway. The Journal of Cell Biology, 2011 193(4), 667-76. (cover) PMID: 21555463
>Highlighted in: The Journal of Cell Biology, Nature Cell Biology, and Faculty of 1000
- Andrade D, Rosenblatt J. Apoptotic regulation of epithelial cellular extrusion. Apoptosis, 2011 16(5), 491-501. PMID: 21399977
- Slattum G, McGee KM, Rosenblatt J. P115 RhoGEF and microtubules decide the direction apoptotic cells extrude from an epithelium. TheJournal of Cell Biology 2009186(5), 693-702. (cover) PMID: 19720875
>Highlighted in Science, The Journal of Cell Biology, and Faculty of 1000
- Rosenblatt J, Cramer LP, Baum B, and McGee KM. Myosin II-dependent cortical movement is required for centrosome separation and positioning during mitotic spindle assembly. Cell 2004, Vol. 117(3): 361-372. (cover)
>Reviewed at Cell, and highlighted in Nature Cell Biology, The Journal of Cell Biology, and Faculty of 1000.
- Rosenblatt J, Raff MC, and Cramer LP An epithelial cell destined for apoptosis signals its neighbours to extrude it by an actin-and myosin-dependent mechanism. Current Biology 2001, 11:1847–1857.
>Reviewed at Current Biology and highlighted in Science, The Journal of Cell Biology, Current Opinion in Cell Biology, and Faculty of 1000.