The rockefeller university

Event Details

Type

Friday Lecture Series

Speaker(s)

Adrian R. Krainer, Ph.D., St. Giles Foundation Professor of Molecular Genetics, Cold Spring Harbor Laboratory

Speaker bio(s)

Dr. Krainer will discuss targeted modulation of alternative splicing by antisense molecules, and its application to understand and treat spinal muscular atrophy. Spinal muscular atrophy is a motor-neuron disease, caused by loss-of-function mutations in the Survival Motor Neuron 1 (SMN1) gene. Patients retain one or more copies of the nearly identical, but splicing-defective SMN2 gene. The small amount of full-length SMN expressed from SMN2 is essential for survival of spinal muscular atrophy patients, but only partially compensates for the loss of SMN1. Together with Isis Pharmaceuticals, Dr. Krainer's lab developed ISIS-SMNRx, an antisense oligonucleotide complementary to a potent splicing silencer in intron 7. This ASO efficiently promotes SMN2 exon 7 inclusion and restores SMN protein levels in various tissues of spinal muscular atrophy mouse models. Dr. Krainer will discuss recent data comparing CNS versus systemic delivery of ISIS-SMNRx in a severe SMA mouse model. Unexpectedly, their results indicate that spinal muscular atrophy is not motor-neuron cell-autonomous, and suggest that correction of SMN2 splicing in peripheral tissues is necessary and perhaps sufficient for phenotypic rescue, at least in the context of the mouse model. Dr. Krainer will also discuss the ongoing clinical trials of ISIS-SMNRx.

Dr. Krainer, originally from Uruguay, received his Ph.D. in biochemistry from Harvard University in 1986, working in the lab of Tom Maniatis. He moved to Cold Spring Harbor Laboratory as a postdoctoral fellow in the lab of Rich Roberts in 1986 and became a faculty member in 1989. He became the St. Giles Foundation Professor of Molecular Genetics in 2009. Dr. Krainer has been on the faculty of the Stony Brook University graduate programs in genetics since 1990, molecular and cellular biology since 1995, biophysics since 2001 and molecular genetics and microbiology since 2012. He has been the program chair of cancer and molecular biology at Cold Spring Harbor Laboratory since 2011. Dr. Krainer has served on numerous editorial boards, including Molecular and Cellular Biology and Protein and Cell, and several advisory boards, including the Broad Hollow Bioscience Park and Isis Pharmaceuticals. He was given the 27th Annual Colleen Giblin Memorial Award and Lecture and the National Institute of General Medical Sciences MERIT Award, among other honors.

Open to

Public

Reception

Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge

Contact

Gloria Phipps

Phone

(212) 327-8967

Sponsor

Gloria Phipps
(212) 327-8967
phippsg@rockefeller.edu