Mark E. Hester, PhD

• Institute for Genomic Medicine
  Principal Investigator
• Primary Department
  Institute for Genomic Medicine

Our team is part of the Institute for Genomic Medicine (IGM) at the Abigail Wexner Research Institute at Nationwide Children’s Hospital, which is at the forefront of using genomic sequencing in the clinical setting to predict best health outcomes for patients and is one of the driving forces shaping precision medicine. We utilize a multidisciplinary approach in our research that encompasses genomic medicine, neuroscience, stem cell biology, biochemistry and molecular genetics to investigate the dynamic nature of the developing brain both in the context of health and neurological disease.

A specific interest of the Hester laboratory is to understand the molecular and cellular basis of pediatric epilepsy such as developmental and epileptic encephalopathy (DEE). DEEs are a class of severe brain disorders associated with early age onset and manifest with intractable and multi-form seizures. While advances in genomic medicine have allowed the identification of de novo genetic variants associated with DEEs, the underlying molecular and cellular mechanisms that cause these disorders are not well understood. Our team is leveraging several key technological tools that include the use of induced pluripotent stem cells (iPSCs), human brain organoid models, genome editing tools, OMICs technologies, and the use of novel transgenic mouse models to address this knowledge gap.

Additionally, our team is investigating molecular mechanisms underlying autism spectrum disorder (ASD) and intellectual disability (ID). Although the causes of ASD and ID are considered genetically diverse, defective synaptogenesis is emerging as a common pathological feature that may account for a significant proportion of these conditions. We are leveraging patient-specific brain organoid models and taking a ‘deep phenotyping’ approach to investigate synaptic disease mechanisms at single-cell resolution, thus enabling the identification of cell-specific responses, compensatory changes, and developmental trajectories underlying the pathophysiology of ASD and ID.

Ultimately, the long-term goal of the Hester laboratory is to rapidly translate research discoveries into lasting treatment options for pediatric patients afflicted with neurological disorders.

Research Interests: Translational Neuroscience, Human iPS Cells, Brain Organoids, 3D Bioprinting, 3D Imaging, Multi-Electrode Array Electrophysiology, Neural Circuitry Modeling, OMICs Technologies, Genome Editing, Bioengineering, Molecular Mechanisms of Epilepsy, Brain Injury, and Autism.

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Publications

Institute for Genomic Medicine