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Project Researcher: Dr Imran Mahmud, Academic Foundation Doctor  

Working in the Nuffield Laboratory of Ophthalmology, Imran has been exploring ways to optimise expression of dual adeno-associated virus (AAV) vectors that are being developed for Stargardt’s disease - an incurable genetic cause of blindness that affects children. Because of the length of the gene associated with Stargardt’s disease (ABCA4), it requires a dual-vector approach whereby the gene is split into two smaller fragments each of which is incorporated into a separate viral vector. By manipulating the viral DNA sequences, the team led by Professor MacLaren is optimising the vectors to carry such large genes in an MRC-funded project. If successful, this technique has potential implications for many gene therapies, including those beyond ophthalmology, in which the gene of interest is too long to be carried by a single viral vector genome.

Imran has also been working on developing new measures of clinical performance in skin cancer surgery. True sensitivity and specificity in a melanoma diagnostic service cannot be ascertained due to the absence of data on true/false negatives. Simply put, we cannot be sure that the lesions we diagnose as non-harmful are in fact histopathologically benign. Surrogate markers must be used to measure specificity and sensitivity. Currently, several measures (benign:malignant ratios, number needed to treat) are frequently being used. They reflect our ability to determine benign lesions from harmful lesions (specificity), but not our ability to detect early (in situ) melanoma. Using histopathological data, our group proposes combining thebenign:malignant ratio (a surrogate for specificity) with the ratio of malignant melanoma:melanoma in situ (a  surrogate for sensitivity) to generate an index which tracks both specificity and sensitivity in diagnosis. The intention is that, using this index, surgeons and services will be able to monitor whether they can avoid excising harmless lesions, and also to catch harmful lesions when they are in the in situ stage.

March 2013

Photo credit: herval via photopin cc unchanged