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Treat Liver Diseases by Targeting Hepatocyte Necroptosis

iMed.ULisboa/ FFULisboa Research Institute for Medicines/ Faculdade de Farmácia, Universidade de Lisboa
Project classification

Scientific area

3.1 Basic medicine

Discipline(s)

Pharmacology and pharmacy
Physiology (including cytology)
Pathology

Project description

Project title

Treat Liver Diseases by Targeting Hepatocyte Necroptosis

Scientific Coordinator's name:

Cecília Maria Pereira Rodrigues

Scientific Coordinator's e-mail:

cmprodrigues@ff.ul.pt

Principal R&D Unit:

iMed.UL/FFUL

Other R&D Units involved in the project:

Instituto de Medicina Molecular, Portugal; Instituto Gulbenkian Ciência, Portugal; Harvard Medical School, Department of Cell Biology, USA

Project keyword(s)

Heme oxygenase-1; Inflammatory liver disease; Necrostatins; Ursodeoxycholic acid

Short abstract and comments

Necroptosis is an alternative form of programmed cell death. Our goal is to define the relative contribution of necroptosis to the pathogenesis of liver damage, dysfunction and failure, associated with different clinical conditions. The hypotheses to be tested under this project are: 1) Modulation of RIP1 signaling by CYLD and its regulator SPATA2 regulates hepatocyte necroptosis and hence the pathogenesis of liver diseases; 2) Pharmacological targeting of RIP1 translates in treatment of liver diseases; 3) Therapeutic UDCA regulates RIP1, CYLD and/or SPATA2 activity to protect hepatocytes from necroptosis, suppressing the pathogenesis of liver diseases in mice and humans; 4) Endogenous protective mechanisms against free heme modulate RIP1, CYLD and/or SPATA2 to protect hepatocytes from necroptosis and suppress the pathogenesis of liver diseases.

Potential uses/indications

The collaborative research under this project should identify novel therapeutic targets for the treatment of inflammation-driven liver diseases, as tested in well-established experimental models. Moreover, the involvement of putative therapeutic targets will be confirmed in patients.

Status

Ongoing

Partner Status: Seeking Partners?

No

Grant number (QREN, FP7, Eureka, etc)

HMSP-ICT/0018/2011

Last edited on

2013-11-04 12:52:19

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