George Gabriel

  • 5th Year Graduate Student

Dissertation Research

Hypoplastic left heart syndrome (HLHS), a severe congenital heart disease (CHD), is associated with high risk for neurodevelopmental disabilities. In fact, over 30% of HLHS survivors experience moderate to severe neurocognitive impairment. While brain abnormalities in HLHS patients are typically thought to be secondary to substrate delivery deficits from circulatory disturbance, we recently recovered the first mouse model of HLHS and found that it also has brain abnormalities suggesting a shared genetic etiology for the heart defects and the neurodevelopmental disabilities. We have observed HLHS mutant mice to display brain abnormalities involving the cortex, hippocampus, and olfactory bulb, forebrain structures also frequently affected in HLHS patients. We have also showed that HLHS and associated brain abnormalities in our mutant mouse line have a digenic etiology, arising from mutations in two genes: Sin3a-associated protein 130 (Sap130), a chromatin modifying protein mediating transcriptional repression, and protocadherin a9 (Pcdha9), a protein involved in cell-cell adhesion. As chromatin modifying genes are already implicated in autism and also in neurodevelopmental impairment in CHD patients, insights into the role of Sap130 in the brain defects of the HLHS mice will have broad relevance for understanding the causes for poor neurodevelopmental outcomes in CHD and non-CHD patients. As a result, using this novel mouse model I am investigating the role of Sap130 in brain development, and how Sap130 deficiency can impair brain development resulting in brain dysmaturation defects and behavioral deficits.

Dissertation Mentor

Dr. Cecilia Lo

Education & Training

  • B.S. Biology, University of Pittsburgh
  • B.A. History, Unversity of Pittsburgh