Hester Lab
The Hester Lab is part of the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital, which is at the forefront of precision medicine and using genomic sequencing in clinical settings to predict best health outcomes for patients. The Hester Lab utilizes 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 Lab 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. The Hester Lab 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, the lab’s 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 Lab is to rapidly translate research discoveries into lasting treatment options for pediatric patients afflicted with neurological disorders.
Meet Our Team
Mark Hester, PhD
Principal Investigator
Mark.Hester@NationwideChildrens.org
Marl Hester, PhD, is a principal investigator in the Institute for Genomic Medicine. He leads a translational neuroscience laboratory focused on understanding the molecular and cellular mechanisms underlying neurological disorders with emphasis on pediatric epilepsy and autism. Dr. Hester is an assistant professor of Pediatrics at The Ohio State University College of Medicine and an affiliate faculty member in the college’s Department of Neuroscience. He is also a member of the Chronic Brain Injury (CBI) Program at Ohio State. Dr. Hester has a widely recognized track record of over 20 years of research on adult and pluripotent stem cells, neurodegeneration, gene therapy, next generation sequencing, reprogramming and in vitro disease modeling.
Dr. Hester first began studying the genetic underpinnings of neurological disease during his postdoctoral fellowship in Dr. Brian Kaspar’s lab in the Center for Gene Therapy at Nationwide Children’s Hospital. His team bioengineered the first in vitro co-culture model of sporadic ALS astrocytes and motor neurons uncovering insights into common disease mechanisms between familial and sporadic ALS, which was published in Nature Biotechnology. Dr. Hester’s passion for understanding neurological disease mechanisms then led to new opportunities in industry where he managed projects focused on bioassay development to functionally validate and screen novel therapeutics.
As a new faculty member in the Institute for Genomic Medicine, Dr. Hester’s research couples his expertise in personalized in vitro models with deep phenotyping approaches to understand underlying mechanisms of neurological disease. His team use state-of-the-art equipment and resources such as electrophysiology, high content imaging technologies and patient-specific glial cell lines, as well as genomics tools such as single cell RNA sequencing, that are foundational to their research program.
Dominic Julian, MS
Research Associate
Dominic is a research associate in the Hester Lab, functioning as the lab manager while also leading projects to better understand the developmental origins of conditions such as epilepsy, Alzheimer’s and autism spectrum disorder.
Dominic received a bachelor’s degree with honors, double majoring in Neuroscience and Psychology, from The Ohio State University in 2016. He received a master’s degree in Physiology from the University of Cincinnati College of Medicine in 2020. Dominic hopes to attend a joint medical and doctorate degree program in the coming years to become a physician-scientist who focuses on care of children and adults with chronic developmental conditions and diseases of aging while running a research lab focused on neuroimmunology.
When not in the lab, Dominic can usually be found running the trails of Columbus in hopes of qualifying for the Boston Marathon, practicing yoga or spending time with his partner and their dog.
Swetha Ramadesikan, PhD
Postdoctural Research Fellow
Swetha is a postdoctoral research fellow in the Hester Lab. She is originally from Chennai, India, and received her bachelor’s degree in Bioengineering there. Following a research internship at the Brigham and Women’s Hospital in Boston, Swetha completed her doctorate degree in Biological Sciences with a concentration in Cell and Molecular Biology at Purdue University.
Swetha’s research is focused on understanding the cellular and molecular mechanisms of epilepsy in a rare genetic disorder called Tuberous Sclerosis Complex (TSC). She is investigating the role of brain pericytes (support cells of the brain vasculature) and their dysfunction in promoting brain calcification and blood brain barrier dysfunction, which is subsequently predicted to lead to epileptic foci in patients.
Summer Fair
Research Assistant
Summer is an aspiring physician scientist who is broadly interested in developmental neurobiology and stem cell technologies. As a member of the Hester Lab, Summer is advancing current understandings of human-specific features of early brain development. She has developed novel methodologies to generate and evaluate forebrain cerebral organoid model systems and is currently using her expertise in human-based model systems and transcriptomic analyses to study the mechanisms of AUTS2 syndrome, pediatric epilepsy syndromes and opioid exposure in the perinatal period.
Prior to her time at Nationwide Children’s, Summer received NIH trainee awards to conduct research on the developing autonomic nervous system at The Ohio State University, the University of Sao Paulo, Brazil, and Lurie Children’s Hospital.
Zubin Shah, MD
Clinical Fellow
Dr. Shah is a clinical fellow in Neonatology with a keen interest in neonatal neuroscience. His fellowship research centers around the use of cerebral organoids and single-cell RNA sequencing to study how opioid exposure changes the developmental trajectory of the fetal brain. Dr. Shah is a Columbus native, and when he’s not in the NICU or in the lab, he can be found brewing coffee or going for a long run.
Wesley Schwind
Research Assistant
Wesley works as a liaison between the Bedrosian and Hester labs by focusing on shared and closely collaborative projects. Wesley obtained his bachelor’s degree in Biology from Cedarville University and has a strong biochemical background studying epileptic mechanisms through modeling and analyzing key protein interactions.
Currently, Wesley continues to investigate the role aberrant neurodevelopmental processes play in causing intractable epilepsy and other neurological disorders through the development and analysis of patient tissue, cell models and cerebral organoid models for the purpose of pinpointing novel therapeutic targets.