Finding genes and pathways behind lissencephaly (smooth brain)

A Gene-Network Discovery Approach to Structural Brain Disorders

NIH-funded research Yale University · NIH-11128731

Researchers will use patient skin cells and laboratory models to find genes and networks that cause lissencephaly in people with this developmental brain condition.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionYale University NIH-funded
Lab location1 site (New Haven, United States)
Project IDNIH-11128731 on NIH RePORTER

What this research studies

You or your child's skin cells would be turned into induced pluripotent stem cells and grown into 2D neural cells and 3D brain organoids so scientists can watch how genes affect brain development. The team will also use embryonic mouse models to study the PIDDosome protein complex and how its malfunction may lead to smooth brain formation. They will analyze genetic data from many patients to find new candidate genes and gene networks, then test those candidates in their cell and organoid models. This combines computer-based gene-network analyses with hands-on lab experiments to link genetic changes to cellular and tissue effects.

Who could benefit from this research

Good fit: People with lissencephaly—or parents of affected children—especially those without a known genetic diagnosis and willing to provide medical records and a skin or blood sample, would be ideal candidates.

Not a fit: People without lissencephaly or whose condition already has a clear genetic diagnosis are unlikely to directly benefit from participating.

Why it matters

Potential benefit: If successful, this work could increase the number of families who receive a genetic diagnosis and point to biological pathways that might be targeted for future therapies.

How similar studies have performed: Previous gene-discovery studies and patient-derived organoid models have identified many lissencephaly genes, so this work builds on established methods while adding novel gene-network analyses and a focus on the PIDDosome.

Where this research is happening

New Haven, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions Brain Diseases
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.