Robert H. Brown, Jr, DPhil, MD, University of Massachusetts
We have had some significant forward momentum in our HSAN1 work. Havisha Karnam has generated a series of chemically modified anti-sense oligonucleotides (small pieces of DNA or RNA that block the production of proteins in the cell) that very clearly suppress expression of SPTLC1 in vitro (in a culture dish). We now have assays pending to ascertain if, as we predict, this also silences expression of the deoxysphingoid bases (backbone of sphingolipids).
In a parallel project, we have generated microRNA that silence expression of the SPTLC1 gene in cells, also in vitro. We are now almost completed packaging this in an adenoassociated virus (AAV) for testing in the HSAN1 mice. We hope to be infusing the mice with the AAV containing the microRNA to silence SPT by the end of June. This has taken longer to get up and running than we anticipated but should nonetheless be accomplished shortly. This is the work of Gaby Toro and Nick Wightman.
A post-doc in the lab, who works on microRNA biology, formerly studied aspects of serine palmitoyltransferase inhibition, ceramide levels and pathology in Alzheimer’s Disease. This individual, Hirosha Geekiyanage, has worked with our chemistry core to see if we can get an assay for the DSB’s (deoxysphingoid bases) running here at UMass and the assay looks like it is clinically very promising. Thorsten Hornemann could not have been nicer about assaying all our samples; however, it will increase our flexibility to have the assay working here.
Additionally, we will have the following people associated with the HSAN1 work:
Hirosha Geekiyanage a post-doc who divides her time between work on the DSB assay and work on ALS microRNA
Sena Agim the post-doc from Purdue (originally Turkey) who joined us in January to work on transcriptome analysis – which would be terrific to do on the HSAN1 mice, and if all goes well the new doctoral student
Huiya Yang – very bright, who wants to work on a combination of silencing of HSAN1 and one of the very new ALS genes. She will be co-mentored by me and by Guangping Gao, the senior scientist who heads our gene therapy unit and who has discovered scores of adeno-associated viruses potentially for human use.
And, until mid-summer, we still have Courtney Pinto, a tech who has done a superb job maintaining the HSAN1 mouse colony. We are sorry to lose Courtney but happy that she will be heading off to medical school.
Let me say that I am very grateful that the Deater Foundation is willing to support this work so generously. We look forward to a strong year in the lab – your support is extremely important and very much appreciated as we start the next year.