Abe and Tara to present at Student Seminar Thursday (9.July) at noon
in CBRB 2289 at noon. I have asked the speakers to provide a brief overview for their talks. Hope to see you there!
Background for Abe’s talk
Hearing impairment is the most common congenital deficit worldwide, affecting at least one of every five hundred neonates. In the Smith Lab, I am working toward gene therapy for hearing loss. Gene therapy targeting the inner ear offers promise for treatment of genetic forms of hearing loss.
There are a variety of cell types within the inner ear. Non-sensory supporting cells of the cochlea serve as the primary targets of intervention to induce hair cell regeneration. Cochlear supporting cells also express GJB2 and GJB6, mutations in which are the most common cause of autosomal recessive non-syndromic hearing loss (DFNB1) in many populations. The promise of hair cell regeneration and the potential for treatment of connexin-related deafness disorders are compelling reasons to identify vectors with tropism for supporting cells of the inner ear.
To target the inner ear we are using embryonic murine otocyst injections, a technique developed and optimized for in utero gene transfer by Bedrosian and colleagues (Mol Ther. 2006 Sep;14(3):328-35). They showed that an adeno-associated viral vector (AAV2/1) will safely and efficiently transduce sensory hair cell progenitors in the embryonic murine otocyst, the precursor to inner ear structures. However, AAV2/1 transduction of supporting cells in the inner ear was significantly less efficient. Given the variety of cell types in the inner ear and the genetic heterogeneity of hearing loss, viral tropism is an important consideration when selecting a vector for gene transfer. In student seminar this week I will report on progress to identify an appropriate vector for safe and efficient in utero gene transfer to the supporting cells of the developing mouse inner ear.
Background for Tara’s talk
Title: Contributions of genes in the complement system to the pathogenesis of atypical hemolytic uremic syndrome
Abstract: Atypical hemolytic uremic syndrome (aHUS, OMIM) is characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. aHUS is far less common and more severe than typical HUS, which is caused by E. coli infection and manifests as diarrheal illness. Anecdotally aHUS is a rare disease with an estimate of a total of 600 cases reported in the USA. The pathogenesis of the disease is linked to dysregulation of the alternative pathway of the complement cascade Mutations in the complement regulators factor H (CFH), membrane cofactor protein (MCP), and factor I (CFI) as well as complement proteins C3 and factor B (CFB), and have been implicated in aHUS. Since only 50 percent of aHUS patients have mutations in known disease causing genes, we hypothesize that there are other genes associated with aHUS. We have chosen to prioritize genes in the alternative pathway as well as the terminal pathway of the complement cascade. The focus of my talk will be to provide an update of the candidate genes that we have sequenced in these patients paying particular attention to those in which we have found interesting variants.
Posted on July 6, 2009, in Student Seminar and tagged abe s., atypical hemolytic uremic syndrome, C3, CFB, CFH, CFI, cochlea, complement system, gene therapy, hearing impairment, MCP, Tara M.. Bookmark the permalink. Leave a comment.