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  Assessment of matrix metalloproteinase 9 inhibitor for the treatment of severe skin-blistering adverse drug reactions using in vitro and ex vivo skin models.


   Institute of Systems, Molecular and Integrative Biology

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  Dr D Carr  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Stevens-Johnson syndrome and toxic epidermal necrolysis are rare, immune-related, severe skin-blistering reactions which can be caused by a wide range of commonly administered drugs. SJS/TEN is characterised by wide-spread skin (epidermal) detachment and recent work in our lab has identified a number of potential molecular mechanism by which this could occur. Furthermore this has highlighted matrix metalloproteinase 9 (MMP9) as a potential therapeutic target for the treatment of skin blistering in SJS/TEN.

The proposed project will utilise previously developed in vitro and ex vivo (clinical skin explants) to further investigate the mechanisms of epidermal detachment in SJS/TEN and screen MMP9 inhibitors with potential as targeted therapies. The student will gain experience of a range of cell/tissue culture techniques and molecular biology protocols (including, western blotting, real-time quantitative PCR and immunohistochemistry).

Under the supervision of Dr Dan Carr, you will work within the state-of-the-art research laboratories of the Wolfson centre for Personalised medicine in the world renowned Dept. of Pharmacology and Therapeutics at the University of Liverpool.

 Our research involves collaboration with a range of academic, clinical and industry partners and you will be expected to engage and work with these partners

The project is suited to a student with at least a good B.Sc. Upper Second in Biological or Life Sciences (particularly pharmacology).

Details of costs can be found on the University website: 

https://www.liverpool.ac.uk/study/postgraduate-research/fees-and-funding/fees-and-costs/


Biological Sciences (4) Medicine (26)

Funding Notes

The project is open to both European/UK and International students. It is UNFUNDED and applicants are encouraged to contact the Principal Supervisor directly to discuss their application and the project. Assistance will be given to those who are applying to international funding schemes. The successful applicant will be expected to provide the funding for tuition fees and living expenses as well as research costs of £10,000 per year. A £2000 ISMIB Travel and Training Support Grant may be available to new self-funded applicants who are paying for their own tuition fees.

References

• Olsson-Brown A Yip V, Ogiji E, Jolly C, Ressel L, Sharma A…, Carr DF. TNF-α mediated keratinocyte expression and release of matrix metalloproteinase 9: putative mechanism of pathogenesis in Stevens-Johnson syndrome/ toxic epidermal necrolysis. J Invest Dermatol. 2023. J Invest Dermatol. 2022 Dec 26:S0022-202X(22)02898-6. Online ahead of print.
• Carr DF, Wang CW, Bellon T, Ressel L, Nwikue G, Shrivastava V, et al. Serum and blister-fluid elevation and decreased epidermal content of high-mobility group box 1 protein in drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis. The British journal of dermatology 2019;181(1):166-74.
• Carr DF, Bourgeois S, Chaponda M, Takeshita LY, Morris AP, Castro EM, et al. Genome-wide association study of nevirapine hypersensitivity in a sub-Saharan African HIV-infected population. J Antimicrob Chemother 2017;72(4):1152-62.

Where will I study?