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Adrian, C., Zettl, M., Christova, Y., Taylor, N., Freeman, M. (2012).
Tumor Necrosis Factor signalling requires iRhom2 to promote trafficking and activation of TACE
Science 335, 225-228.
Zettl, M., Adrain, C., Strisovsky, K., Lastun, V., and Freeman, M. (2011).
Rhomboid Family Pseudoproteases Use the ER Quality Control Machinery to Regulate Intercellular Signaling.
Cell 145, 79-91.
Aldaz, S., Escudero, L. M., and Freeman, M. (2010).
Live imaging of Drosophila imaginal disc development.
Proc. Natl. Acad. Sci. U S A 107, 14217-14222.
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The main questions we study are what cellular mechanisms regulate signalling between animal cells, and how does that signalling control biological functions like development and physiology?
Our focus recently has been on the rhomboid family of proteins. We initially discovered that rhomboids were novel intramembrane proteases, conserved across evolution, which regulate the production of extracellular signals. More recently we have become interested in non-catalytic rhomboid-like proteins, which we have found to function in the endoplasmic reticulum, where they control the fate of specific membrane proteins.
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We study the genetics, cell biology and biochemistry of rhomboid-like regulation and function, using a variety of systems including Drosophila, mice and human cells. Although our main effort is aimed at understanding fundamental biology, we are also pursuing the potential medical significance of our basic discoveries, which includes cancer, inflammation, metabolic disorders and infectious diseases.
In complementary approaches, we also use Drosophila genetics to investigate the cellular mechanisms and biological consequences of intercellular signalling. For example, we are studying the role of more distant members of the rhomboid family in regulating growth factor signalling and, in another project, how interplay between tumour cells and their environment can control metastasis.
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