Molecule Discovery by University of Birmingham Scientists Holds Promise for Gene Therapies for Psoriasis

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The protein is a fragment of a larger molecule, called JARID2, which was previously believed to only be present in the developing embryo, where it coordinates the formation of tissues and organs.

However researchers led by Dr Aditi Kanhere from the School of Biosciences found a shortened form of JARID2 in adult skin cells, and they showed it is responsible for ensuring these skin cells 'differentiate' (become a more specialised cell type).

They dubbed the newly discovered protein N-JARID2. 

The significance of this finding was immediately recognised by Dr Kanhere's team, which studies how gene expression is regulated in normal and diseased conditions.

Dr Kanhere explains: "In some diseases, cells lose their ability to differentiate, and divide more rapidly. Being able to redirect cells back to their usual life cycle could alleviate the processes behind the disease."  

This is the case with psoriasis, which is caused by the rapid division of skin cells.  These excess cells are then pushed to the surface of the skin too quickly, resulting a build-up of cells that aren't fully mature on the surface of the skin, and causing flaky, crusty red patches covered with silvery scales.  

Dr Kanhere's research, published today in EMBO Journal, shows that N-JARID2 is present in the skin layers, where it is responsible for ensuring that the tissues maintain their usual state of differentiation which is necessary to properly form skin layers.

The discovery has caught the eye of the patenting team at University of Birmingham Enterprise, who filed a broad-based patent covering the use of N-JARID2 in therapies aimed towards conditions caused by hyper-proliferation of skin cells such as psoriasis.

The research team is now investigating how N-JARID2 is generated and its wider implication in disease, while the patenting team hopes that this discovery will ultimately lead to novel therapies for skin conditions.

About the research

The research was supported by the Wellcome Trust Institutional Strategic Support Fund, the University of Birmingham, and the Islamic Development Bank.  

The research team investigated JARID2 expression in lineage committed human cells. JARID2 is a Jumonji family of protein which plays a central role in regulating how genes are expressed.  Dr Kanhere's group detected a ~80 kDa protein that had not been reported previously, and identified it as a C-terminal cleaved product of full-length JARID2.  They named the protein N-JARID2 and characterised its action in in vitro studies using adult human keratinocytes.  

In these cells, the level of N-JARID2 increases as differentiation of keratinocytes progresses.  The research team demonstrated that decreased expression of epidermal genes in JARID2-null cells can be reversed by expression of the C-terminal fragment alone.  

It was formerly believed that JARID2 was not expressed, or expressed at very low levels in lineage committed cells.  

Reference

Kanhere et al (2018).  A Novel Form of JARID2 is Required for Differentiation in Lineage-Committed Cells.  EMBO Journal.  DOI:  10.15252/embj.201798449

About the patent 

University of Birmingham Enterprise has filed a broad-based patent covering the protein, its functional fragments, and analogues, and its use in treatments for benign hyperproliferative skin disorders including psoriasis, common warts, keratoacanthoma, seborrhea, ichthyosis, actinic keratosis, Bowen's Disease, papilloma, seborrhoeic keratosis, eczema, atopic dermatitis, keloids, and Epidermolysis Bullosa (EB).

The University of Birmingham's patented technologies are showcased on the IN-PART website.  

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