Understanding Neurodevelopmental Disorders

Technology Overview

Dr. Kimberly Aldinger

Alterations in brain and vascular development caused by genetic variants can lead to brain malformations and conditions including autism, cerebral palsy or epilepsy. Neurodevelopmental expert Kimberly Aldinger, PhD, integrates multiomic and phenotypic analyses with cell- and tissue-culture modeling — including brain organoids — to identify intervention targets for these conditions. Her ultimate goal is improving the lives of children with neurodevelopmental disorders.

Dr. Aldinger investigates the genetic and cellular mechanisms of brain development, with a priority focus on the cerebellum, which is involved in motor control and cognitive functions. She and her team have expertise in advanced systems-level methods such as exome sequencing, single-cell RNA sequencing and spatial transcriptomics. The team is also experienced in 3D-imaging methods including confocal microscopy and light-sheet microscopy. These techniques allow the Aldinger Lab to visualize the architecture of intact brain structures from patient samples, using multiple biomarkers to detect specific cell types and their individual components.

The Aldinger Lab applies the resulting data to create customized preclinical models for determining the mechanisms by which gene variants cause developmental disorders. The team also generates public resources such as the Developmental Cell Atlas of the Human Cerebellum, which maps genetic variants that are involved in developmental disorders onto the cells most affected by the mutations. Dr. Aldinger has expertise in:

• Establishing and studying brain cells cultured from patient samples, such as:
  1. cell lines of differentiated neurons for assays of activity and function that reveal potential drivers of seizures and other patient phenotypes and
  2. 2D and 3D models that demonstrate the complex cellular compositions and interactions of cerebellar and vascular tissues.
• Using induced pluripotent stem cells (iPSCs) to create early brain neuroprogenitor cells or brain organoids, particularly for representing the cerebellum.

The preclinical models from the Aldinger Lab could be used to test existing drugs for indication switching to treat seizures and other consequences of developmental disorders. Several genetic variants that Dr. Aldinger is investigating are candidates for indication expansion of kinase-inhibitor drugs. Other variants have gain-of-function or dominant-negative mutations and thus might be treatable with expression-modulating therapeutics such as antisense oligonucleotides. Genes that the Aldinger Lab are studying encode:

• MAST4, a microtubule-associated serine/threonine kinase that is similar to the tau protein associated with Alzheimer’s disease. This kinase is a potential target for epilepsy therapy.
• PDGFRB, a tyrosine kinase receptor for platelet-derived growth factor (PDGF) that the Aldinger Lab discovered can contribute to cerebellar hypoplasia through specific gain-of-function mutations.
• AUTS2, a regulator of heterochromatin. Some variants are associated with autism spectrum disorder, developmental delay and intellectual disability.
• FOXC1 and FOXP1, members of the FOX gene family of transcription factors that can cause brain malformations and developmental disabilities.

Dr. Aldinger is interested in industry partnerships to identify actionable pathways and factors that are potential targets for therapies for children with rare genetic brain disorders.

Stage of Development

• Preclinical in vitro
• Preclinical in vivo
• Preclinical ex vivo

Partnering Opportunities

• Collaborative research and development
• Sponsored research agreement
• Consultation agreement
• Collaborative animal model development

Learn More

• Kimberly Aldinger, PhD
• Aldinger Lab
• Developmental Cell Atlas of the Human Cerebellum

Publications

1. Dekker J, Schot R, Aldinger KA, et al. A clinical and genotype-phenotype analysis of MACF1 variants. Am J Hum Genet. 2025;112(10):2363-2380.
2. Erdogan EN, Cheng CV, Caraffi SG … Aldinger KA. Further delineation of the AUTS2 HX repeat domain-related phenotype. Am J Med Genet A. 2025;197(9):e64093.
3. Sun X, Menon S, Wambo P … Aldinger KA, et al. Epigenomic landscape of the developing human rhombic lip reveals gene regulatory network and non-coding loci of developmental, evolutionary, and disease relevance. bioRxiv [Preprint]. 2025:10.30.685586.
4. Chen Y, Bury LA, Chen F, Aldinger KA, et al. Generation of advanced cerebellar organoids for neurogenesis and neuronal network development. Hum Mol Genet. 2023;32(18):2832-2841.
5. Aldinger KA, Timms AE, Thomson Z, et al. Redefining the etiologic landscape of cerebellar malformations. Am J Hum Genet. 2019;105(3):606-615.

Last updated May 2026