Gerarda Cappuccio is a physician/scientist and a postdoctoral fellow at Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital. She is a pediatrician subspecialized in genetics interested in neurodevelopmental metabolic disorders. Her goal is to find treatments for patients with untreatable genetic conditions. She discovered two new syndromes and coordinated clinical trials for them, leading to her receiving the 2022 John M. Opitz Young Investigator Award. She is now leveraging her clinical background and translational research experience to investigate the mechanisms of rare genetic syndromes, including copy number variants in 16p11.2 locus. She uses human models of disease, from brain organoids to organs-on-a-chip, to study how perturbations of metabolism affect neurogenesis and neuronal function. Utilizing a variety of new technologies from spatial transcriptomics and spatial metabolomics to nanoparticles for delivery of small molecules, her work paves the way toward new discoveries important for gene and pharmacological therapies. Cappuccio has published extensively, with 77 papers (30 as a first author), and received several awards for her work. She is also a keen mentor of undergraduate and graduate students, and actively promotes diversity and young women interested in STEM careers.
Principal Investigator: Mirjana Maletic-Savatic
Undergraduate Fellow Project: Mapping cell type-specific lipid dysregulation in 16p11.2 deletion syndrome
Lipids are a broad class of species essential for proper cell structure, energy metabolism and signaling, playing critical role in brain cell function. Our lab studies neurogenesis and how lipid metabolism affects generation of neurons during early development, adulthood and in disease. Here, we focus on the 16p11.2 deletion syndrome that arises because of copy number variations of the 16p11.2 genetic locus, causing several neurodevelopmental and psychiatric disorders. This locus contains different genes associated with lipid metabolism regulation (FAM57B, FBP2, ALDOA), and we hypothesize that deletion of these genes leads to cell type (neuron, astrocyte, neuroprogenitor)-specific lipid dysregulation manifesting in aberrant cell type-specific function and activity. We will test this hypothesis in forebrain organoids from patients with 16p11.2 deletion and isogenic controls. We will identify which lipid classes are most perturbed using cell-type specific lipidomics and imaging mass spectrometry. We will correlate these data with single cell transcriptomics and spatial transcriptomics, to identify specific pathways perturbed in 16p11.2 deletion. Further, as lipids are major part of cell membranes, we will perform atomic force microscopy to examine cell type-specific membrane properties. This project will thus provide broad scholarship and technical knowledge about the gene/metabolome dysregulation and brain function in 16p11.2 deletion.