CURE SYNGAP1 501(c)(3) is pleased to announce a $130,000 grant to Dr. Helen Willsey and Dr. David Kastner at the University of California, San Francisco (UCSF). This funding extends Dr. Willsey's identification of SYNGAP1's role in cilia formation to investigate how its disruption impacts brain anatomy and behavior, potentially leading to more precise therapies for patients with SYNGAP1-Related Disorders (SRD).
Building on previous discoveries that SYNGAP1 protein localizes to both primary and motile cilia, the research will use rodent models to investigate the link between SYNGAP1 protein deficiency, cilia dysfunction, and the diverse clinical symptoms seen in SRD patients, including intellectual disability, gastrointestinal issues, and behavioral changes. The work spans analysis from subcellular ciliary phenotyping to behavioral characterization in genetically modified rats with two different alterations to the Syngap1 gene. Investigation and analysis will be done with an eye towards informing rational drug design.
Why we supported this project
CURE SYNGAP1 is committed to improving the lives of all SRD patients. SYNGAP1-Related Disorders include many symptoms that may not solely result from cortical synaptic plasticity deficits. Moreover, it is increasingly clear that SYNGAP1 expression extends beyond the brain. Findings outlined in Dr. Willsey's preprint on bioRxiv underscore the importance of addressing the multifaceted impact of SYNGAP1 mutations. This preliminary data offers a compelling path forward, providing deeper insights into the diverse roles that SYNGAP1 protein plays in the body. Her work has the potential to broaden the range of tissues targeted by therapies, addressing many unmet medical needs affecting our patients. By uncovering previously overlooked functions of the SYNGAP1 protein, this project will also help us mitigate unintended consequences of future therapies. Additionally, her research will aid in categorizing missense variants by their functional characteristics, which is crucial for identifying the most effective precision medicine strategies for each variant.
Past work by Dr. Helen Willsey
Dr. Helen Willsey's lab at UCSF has made significant advances in understanding SYNGAP1 protein functions beyond the synapse. Her research, using Xenopus models, uncovered SYNGAP1 protein's critical role in ciliogenesis, providing crucial insights into how SYNGAP1 mutations affect both neural and non-neural tissues. These groundbreaking findings form the foundation for her current work, which now extends into rodent models, aimed at investigating how SYNGAP1 mutations impact brain structure and broader systemic functions.
Powerful story of partnership
"We have been giving grants for eight years, Dr. Willsey sets the bar for collaboration, productivity, brilliance and actually listening to patient families. She is simply exceptional. The SYNGAP1 community is very lucky to work with her and those in her lab" said Mike Graglia, Founder and CEO, (who generally always has some constructive feedback for grantees).
What the team is saying
Dr. Helen Willsey shared her gratitude for the support provided by CURE SYNGAP1, stating, "We are immensely grateful for the generous support provided by [CURE SYNGAP1], which empowers us to delve deeper into the intricacies of SYNGAP1 function across a wide range of organs and tissues, and how this manifests behaviorally. This funding serves as a catalyst for our multidisciplinary team of researchers, and the findings generated through this research have the potential to inform the development of targeted therapies, paving the way for more effective treatments and improved patient outcomes."
Dr. Matthew State, MD, PhD, Oberndorf Family Distinguished Professor and Chair of UCSF's Department of Psychiatry and Behavioral Sciences, highlighted the significance of Dr. Willsey's work: "Dr. Willsey's research has been instrumental in expanding our ability to identify high-confidence, large-effect risk genes for psychiatric disorders such as autism spectrum disorder, Tourette disorder, and obsessive-compulsive disorder. I am confident that, in partnership with CURE SYNGAP1, her lab will make an equally large impact on our understanding and treatment of SYNGAP1-related conditions."
Kathryn Helde, PhD, Chief Scientific Officer for CURE SYNGAP1, added excitement about addressing the unmet need of relieving patients and families from debilitating behaviors. "This research includes analyzing the rich social behaviors seen in rats, and comparing them to rat models of SRD. The chance to identify specific targets for drugs that improve behaviors is one of our top priorities."
Family donations make progress possible
Research like Dr. Willsey's is exactly what our community needs right now. It's focused on solving the everyday challenges families face and offers real hope for improving quality of life. This work shows the impact we can have when science and community support come together."
Suzanne Jones, Chair of the CURE SYNGAP1 Board of Trustees
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