ESR14: Pharmacological protein folding manipulations of ABCA4 mutations
University College London, United Kingdom (www.ucl.ac.uk)
Dr. M. Cheetham
I am 24 years old and I am from Naples (IT). I have a master's degree in Biology and I pursued my master's thesis at TIGEM. During this period I investigated the protective effect exerted by the modulation of MicroRNAs miR-181a/b in models of photoreceptor degeneration. I am currently working with professor Mike Cheetham at UCL.
The majority of ABCA4 mutations found in STGD1 are missense mutations. Many of those that have been studied in detail (for example R602W, L541P) lead to protein misfolding, endoplasmic reticulum (ER) retention and protein degradation, leading to loss of function. Missense mutations in the related ABC transporter CFTR are also prone to misfolding and respond well to pharmacological manipulation to improve folding and restore function. P8-UCL has a great deal of experience of manipulating mutant rhodopsin folding, degradation and aggregation both in cells and in vivo. Therefore, we believe that ABCA4 will also be amenable to pharmacological protein folding manipulation. ESR14 will test pharmacological approaches that are effective for CFTR and mutant rhodopsin for their ability to rescue mutant ABCA4 folding, traffic and function. ESR14 will use a combination of heterologous expression of ABCA4 mutants in cell culture and human iPSC derived 3D retinal organoids that express endogenous mutated ABCA4 for these studies to provide direct proof of concept for pharmacological manipulation of ABCA4.Paragraph. Haz clic aquí para editar.