SMSRF excited to announce newest project at The University of Michigan

“The Sutton and Iwase laboratories have a joint mission to uncover chromatin regulatory mechanisms that underlie Smith Magenis Syndrome (SMS). Our hope is that a complete understanding of these mechanisms will reveal specific alterations in the brain that give rise to core symptoms of SMS, and importantly, guide the development of novel treatment approaches. Our group bring complementary expertise to this mission – the Sutton laboratory has spent years studying molecular mechanisms that control information transfer across synaptic connections in the brain, while the Iwase laboratory has uncovered key ways in which neuronal activity modifies chromatin to control gene expression and neuronal function.

Our recent work has focused on the SMS causative gene Retinoic Acid Induced-1 (RAI1), and its role in regulating changes in neuronal gene expression that typically allow neurons to fine-tune synaptic connections to buffer destabilizing activity in neural circuits. We have found that RAI1 is critical for preventing inappropriate activation of these gene expression programs when neural circuit activity is stable, and we will determine whether loss of this key checkpoint contributes to altered brain development in SMS. Our ongoing work uses a combination of cutting-edge technologies to identify RAI1 target genes in neurons, the degree to which these RAI1 targets are unique to human vs. rodent neurons, and how these target genes act to fine-tune synaptic function. We are excited for the potential of these studies to identify new RAI1 regulated genes that can be targeted for future treatment of SMS.” –

Michael Sutton, PhD
Professor of Molecular and Integrative Physiology

Shigeki Iwase PhD
Associate Professor of Human Genetics