WHAT RESEARCH DOES LOUIE’S HUWE SUPPORT?

Key areas of research into HUWE1 that Louie's Huwe currently supports include…​

• Clinical research with Kristin Barañano, M.D., Ph.D., at John's Hopkins University School of Medicine. This involves a structured clinical interview, to better understand HUWE1-related symptoms and to guide clinical management. Contact us for more information about participating.

• Laboratory research at the Grill Lab at Seattle Children’s Research Institute with Louie’s Huwe Scientific Advisor, Brock Grill, Ph.D. See below for details.

• Laboratory research at the Page Lab at Seattle Children’s Research Institute with Damon Page, Ph.D. See below for details.

• The HUWE1 Data Collection Program, powered by RARE-X. This includes patient reported surveys, collating symptoms and providing anonymised access for researchers around the world. Patients can take part at: https://huwe1.rare-x.org/

You can learn more about our scientific advisors here: Louie's Huwe Team.

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MORE ABOUT LOUIE'S HUWE SUPPORTED RESEARCH PROJECTS...

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Grill Lab: HUWE1 research at Seattle Children’s Research Institute, supported by Louie's HUWE

Who is carrying out the research?

Brock Grill, Ph.D. is a professor and principal investigator actively researching HUWE1 and a Louie’s Huwe Board Member. His work focuses on understanding how information is relayed within nerve cells to regulate cellular activities and animal behavior using the microscopic worm C. elegans. Dr. Grill and his team at Seattle Children’s have been studying the role of HUWE1 in the nervous system for the past twelve years. He is a professor at the University of Washington Medical School and at the Seattle Children’s Research Institute, USA.

What does the research involve?

As a laboratory-based program, this research aims to use a microscopic nematode, C. elegans, to study HUWE1 gene function. C. elegans is a highly tractable model for both genetic and pharmacological studies on HUWE1 (also called EEL-1 in C. elegans). The Grill lab’s work has shown that HUWE1 is required to preferentially regulate the nerve cells that quiet the nervous system. Dr. Grill is now using CRISPR gene editing to examine how human genetic variants in HUWE1 affect gene function in C. elegans. His team is also working towards developing humanized HUWE1 C. elegans models, and using large-scale pharmacological studies to identify small molecules targeting HUWE1.

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What are the benefits?

This research will increase our understanding of how human variants in HUWE1 affect gene function, and test whether individual human variants in HUWE1 are pathogenic, supporting causative diagnosis for individual patients. Pharmacological outcomes have the potential to identify new therapies for kids with HUWE1-associated neurodevelopmental disorder.

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Page Lab: HUWE1 Research at Seattle Children’s Research Institute, Supported by Louie’s HUWE

Who is carrying out this research?

Damon Page, Ph.D., is a professor and principal investigator at Seattle Children’s Research Institute. Over the past 25 years, Dr. Page has dedicated his research career to advancing our understanding of the causes and potential treatments for neurodevelopmental disorders, including autism spectrum disorder and intellectual disability. From his early training at the University of Cambridge, through postdoctoral work at the Massachusetts Institute of Technology, and later leading his laboratory at The Scripps Research Institute in Florida, Dr. Page has been driven by the urgent need for better diagnostic and treatment options for individuals and families affected by these conditions. His lab has made significant progress in studying two rare genetic disorders linked to autism and intellectual disability, caused by mutations in the PTEN and DYRK1A genes. Through this work, they have uncovered key mechanisms underlying abnormal brain and behavioral development, identified therapeutic targets, and conducted preclinical testing of small molecules and biologics that may help alleviate symptoms relevant to patients. Dr. Page is now excited to apply these successful approaches to understanding and addressing the needs of individuals and families affected by HUWE1-associated neurodevelopmental disorder.

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What does the research involve?

This laboratory-based research aims to use CRISPR gene-editing technology to create a mouse model carrying the specific genetic variants found in patients with HUWE1-associated neurodevelopmental disorder. This mouse model will serve as a valuable tool to study how these variants impact brain development and behavior. Additionally, this work will complement ongoing HUWE1 research, such as the C. elegans studies led by Brock Grill, Ph.D., also at Seattle Children’s. Future stages of this research will focus on characterizing the HUWE1 mouse model, particularly looking at key symptoms observed in patients, such as seizures, microcephaly (small head size), and white matter abnormalities in the brain.

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What are the benefits?

The primary goal of this research will be the creation of the first mouse model that accurately represents a patient-specific variant in the HUWE1 gene. This model will be crucial for understanding how HUWE1 variants disrupt brain development, providing insights that could lead to new therapeutic approaches. Additionally, this model will be a critical tool for preclinical testing of potential treatments, an essential step toward developing effective therapies for patients. Initial studies using this model will also evaluate key symptoms seen in HUWE1-associated neurodevelopmental disorder, including seizures, microcephaly, and white matter abnormalities. This will pave the way for future preclinical research, with the long-term aim of translating the findings of this work into clinical trials.

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Through research we aim to further understanding of HUWE1. Our international HUWE1 community, fundraising and voluntary board is what makes this possible - thank you for your support.

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