Our Research

Nutrition and Neurodevelopment Activity

Nutrition and Infant Neurodevelopment

Nutrition has profound impact on neurodevelopment, but the mechanisms are only partly understood. In collaboration with other researchers at the Fetal-Neonatal Neuroimaging Developmental Science Center, we are studying the connections between maternal diet, breastmilk contents, infant brain development and child neurodevelopment. We also have a pilot study on the trajectory of infant develop the important skill of oral feeding with the goal of improving diagnosis and personalized care through quantitative EMG assessment of infant feeding, advanced computational analytics, and identifying biomarkers of neonatal outcomes.

Neurodevelopment FreeSurfer

Modifiers of Neurodevelopment among Patients with Congenital Heart Disease

Congenital heart disease (CHD) is the most common severe malformation. As improvements in medical and surgical management have led to increased survival, patients with congenital heart disease face additional lifelong health risks. Neurodevelopmental delay or impairment is the most common extracardiac complication of CHD. To better understand the mechanisms of neurodevelopmental risk in patients with CHD, we have recently participated a clinical trial that collected genetic, clinical, and neuropsychological testing data. Ongoing projects include further analysis of that trial data, and local pilot studies.

Gene Discovery Data

Gene Discovery in Congenital Heart Disease

We study the genetics of congenital heart disease with the goal of improving diagnosis and personalized care through gene discovery, functional analysis of patient variants, and identifying biomarkers of neonatal outcomes. Approaches include computational biology projects, cell culture projects, and multi-omic analysis of patient samples.

Publications

  • Lanners, N., Morton, S. U., Le, K., Blanco, S., Mansoorshahi, S., Carreon, C. K., Ronai, C., Wilkins-Haug, L., Annavajjhala, V., Parchem, J. G., & Findley, T. O. (2026). Placental Dysfunction and Congenital Heart Disease: Investigating the Placenta-Heart Axis.. Prenatal Diagnosis. https://doi.org/10.1002/pd.70194 (Original work published 2026)
    Publisher's Version
    Publisher's Version

    OBJECTIVE: Concurrent development of the placenta and heart during early gestation suggests a shared biological basis for the co-occurrence of abnormal placentation and congenital heart disease (CHD). This study investigated the association between placental vascular pathology and CHD type.

    METHODS: A retrospective study at two institutions included CHD (n = 521) and unaffected (n = 122) infants. CHDs were categorized into three groups (left and right ventricular outflow tract obstruction and mixed lesions) based on the anticipated effect of placental venous return streaming toward the fetal brain. Placental pathological findings were categorized by the Amsterdam criteria. The rate of placental pathology was compared between cases and controls and across the three CHD groups.

    RESULTS: CHD had higher rates of maternal vascular malperfusion (MVM) (0.31 vs. 0.05, p < 0.001). Comparison within CHD groups demonstrated similar rates of MVM, while fetal vascular malperfusion (FVM) was significantly higher in groups with reduced fetal cerebral oxygenation (p = 0.037). MVM was associated with low birth weight (OR = 0.28, p < 0.001), and FVM was associated with increased maternal age (OR = 1.07, p = 0.037). No significant associations were identified in other placental pathologies.

    CONCLUSION: This study offers valuable insights into the connection between placental dysfunction and CHD, identifying that MVM is significantly associated with CHD development.

  • Ladha, F. A., Avillach, P., Opotowsky, A. R., Nael, A., Brueckner, M., Chung, W. K., Cnota, J. F., Gelb, B. D., Lewis, M., Liu, C., Roberts, A. E., Seidman, C. E., Seidman, J. G., Tristani-Firouzi, M., Wagner, M., Newburger, J. W., Kim, Y., & Morton, S. U. (2026). Rare KDR Variants Define a Distinct Genetic Contribution to Congenital Heart Disease.. Circulation. Genomic and Precision Medicine, e005659. https://doi.org/10.1161/CIRCGEN.125.005659 (Original work published 2026)
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    Publisher's Version
  • Movassagh, M., Newbury, L., Hehnly, C., Whalen, A. J., Peterson, M., Mondragon-Estrada, E., Ericson, J. E., Smith, J., Sasanami, M., Natukwatsa, D., Mugamba, J., Ssenyonga, P., Onen, J., Burgoine, K., Zhang, L., Olupot-Olupot, P., Kumbakumba, E., Wegoye, E., Ochora, M., … Schiff, S. J. (2026). Genome admixture analysis of 1,030 Ugandan infants with neonatal sepsis and hydrocephalus demonstrates geographical stratification of population disease risk.. MedRxiv : The Preprint Server for Health Sciences. https://doi.org/10.64898/2026.03.16.26348489 (Original work published 2026)
    Publisher's Version
    Publisher's Version

    BACKGROUND: Neonatal disorders such as post-infectious hydrocephalus exhibit a higher incidence in Africa, where the intricate relationships between genetic ancestry, environmental exposures, and other risk factors likely contribute to the increased incidence.

    METHODS: To start to characterize the common genetic architecture of Ugandan infants, we analyzed genome sequencing data from 1,030 Ugandan infants recruited from studies targeting neonatal sepsis and hydrocephalus. We employed genetic admixture analysis and integrated geospatial data to examine the relationships between genetic backgrounds and disease prevalence within this cohort.

    RESULTS: Our results identified four distinct genetic admixture groups, each correlating strongly with specific geographic distributions across Uganda. Notably, a predominance of one admixture group, most common in northern Uganda, was overrepresented in the participants with post-infectious hydrocephalus.

    CONCLUSION: This study underscores the importance of genetic factors in disease manifestation at the population level, and a role for such precision public health approaches in complex neonatal disorders in African populations.

  • Lee, J., Wu, J., Pittman, M., Grant, Z. L., Kuang, S., Quiat, D., Morton, S. U., Fudenberg, G., Traglia, M., Hayes, K. A., Consortium, P. C. G., Kumar, R., Bruneau, B. G., & Pollard, K. S. (2026). Structural variants in human congenital heart disease disrupt distal genomic regulatory contacts of developmental genes.. BioRxiv : The Preprint Server for Biology. https://doi.org/10.64898/2026.02.28.708767 (Original work published 2026)
    Publisher's Version
    Publisher's Version

    Predicting the functional significance of structural variants (SVs) associated with genetic diseases remains challenging. To test the hypothesis that SVs from people with congenital heart disease (CHD) disrupt developmental chromatin interactions, we developed CardioAkita, a machine-learning model that predicts how variants alter 3D chromatin structure. Analyzing previously genotyped de novo SVs ( dn SVs), we observed a positive association between CHD severity and CardioAkita scores across dozens of families. From whole-genome sequencing of three individuals with CHD we predicted disruptive dn SVs. Induced pluripotent stem cells engineered to harbor these variants confirmed CardioAkita's predictions of 3D chromatin changes, and further revealed aberrant expression of local genes including cardiac developmental genes, suggesting that chromatin reorganization plays a significant mechanistic role in the genetic etiology of CHD. Our findings highlight the potential for models of 3D chromatin organization to predict the pathogenicity and underlying mechanisms of SVs in human disease.