Description of Clinical Expertise

Fetal and Neonatal Neurology

Description of Research Expertise

Research Interests:
The Cristancho lab is interested in understanding the epigenetic mechanisms driving long-term neurodevelopmental disabilities from acquired prenatal and perinatal brain injury. We posit that even in the setting of little cell death, epigenome disruption during critical stages of early brain development persistently alters brain maturation and function.

Keywords:
prenatal brain injury, epigenetics, neurodevelopmental disorders, multi-omics, behavior, translational, hypoxia

Research Details:
Prenatal and perinatal brain injuries, including prenatal hypoxia, are among the most common causes of neurodevelopmental disabilities worldwide, ranging from developmental delays, autism, epilepsy, cerebral palsy, and learning disabilities. However, despite their prevalence, we have almost no directed therapies for these disorders. Part of the challenge is that these injuries are variable in what causes them, how long the insult lasts, and lead to a wide variety of disabilities in affected children.

To study these questions, we use a combination of animal and cell culture models and take advantage of multi-omic approaches to garner a multi-dimensional understanding of these complex brain injuries on different cell types. We then use physiologic, behavioral, and imaging outputs to link changes in the epigenetic signature to functional outcomes to determine which changes to the epigenome are important for modulating the severity of neurodevelopmental deficits after developmental brain injury.

We are currently focusing on a model of transient prenatal hypoxia, where we found there is little early cell death, but there are persistent deficits in adult animals (decreased seizure threshold and other behavior anomalies). Using single nucleus RNA-seq and ATAC-seq, we are currently unraveling the cell type-specific dynamics that drive these persistent functional deficits long after the insult has occurred.

Rotation Projects:
Please contact us for a discussion of possible rotation projects.