Research
Three interconnected programs investigating how prematurity impacts the developing brain.
Prematurity and Neurodevelopmental Outcomes
Our prematurity research program employs a comprehensive translational approach combining human tissue analysis with innovative mouse models to understand how early birth disrupts brain development. Using our unique biorepository of cerebellar tissue samples from 98 human neonates, we apply cutting-edge spatial transcriptomics, electron microscopy, and biochemical analyses to characterize how maternal immune activation (MIA) and hypoxia—the major insults of prematurity—induce cellular and molecular abnormalities in the developing brain.
Our preliminary data reveal that preterm birth results in decreased cerebellar growth, Purkinje and Granule cell developmental arrest with reduced differentiation and migration, mitochondrial injury leading to shifts in metabolic states, and increased inflammatory markers with lymphocyte infiltration of the cerebellar cortex. Complementing these human studies, our MIA and hypoxia mouse models of prematurity allow us to evaluate targeted therapeutic interventions. Comprehensive neurobehavioral and coordination analyses demonstrate that physiotherapy and environmental enrichment can significantly improve motor outcomes, cognitive function, and cerebellar-dependent coordination tasks.
This bidirectional translational approach—from human tissue discovery to animal model validation and back to clinical application—enables us to identify both the mechanisms of injury and evidence-based therapeutic strategies to optimize neurodevelopmental outcomes in preterm infants.
Necrotizing Enterocolitis and Brain Injury
Our NEC research investigates how this severe intestinal complication of prematurity extends beyond the gut to affect the developing brain, addressing critical knowledge gaps about the nature and regional distribution of NEC-associated neurological injury. Through comprehensive analysis of postmortem tissue and neuroimaging from infants with NEC compared to matched controls, we have identified selective vulnerability of the pons—a brainstem region critical for functions consistently impaired in NEC survivors, including feeding coordination, suck-swallow-breath synchronization, and auditory processing.
Our preliminary data demonstrate that infants with NEC exhibit a ninefold greater likelihood of pontine hypoplasia, with complementary neuropathologic and transcriptomic profiling revealing selective neuronal loss and enrichment of immune pathways. We employ spatial multi-omic approaches integrating in situ transcriptomics with immune-focused proteomics in paired brain and intestinal tissue to map how intestinal inflammatory signals breach the blood-brain barrier at vulnerable regions, triggering region-specific neuronal injury.
By combining these tissue-anchored discoveries with plasma proteomics and brain ultrasound in surviving infants, we are developing clinically accessible biomarkers that link anatomically defined injury mechanisms to bedside assessment tools, ultimately aiming to improve prognostication and guide neuroprotective interventions for this devastating complication.
Sudden Infant Death Syndrome in Preterm Infants
Our SIDS research program explores why prematurity increases SIDS risk more than fourfold, focusing on how early birth disrupts cerebellar-brainstem circuits essential for cardiorespiratory control and arousal responses. Recognizing that the cerebellum undergoes critical maturation during the third trimester—the period most disrupted by prematurity—we investigate how prematurity-associated immune activation and developmental disruption compromise the circuits that normally restore arousal, blood pressure, and respiration during hypoxic stress.
Our preliminary analyses comparing preterm SIDS to matched preterm non-SIDS cerebella reveal gestational age-associated alterations in developmental and neuron-glia molecular pathways, suggesting that disrupted cerebellar neuroimmune regulation underlies vulnerability. Using advanced spatial transcriptomics with single-cell and subcellular resolution in our well-phenotyped cohort, which includes detailed maternal, perinatal, and clinical characteristics, we map how prematurity-linked immune signatures connect to the disrupted maturation of specific cerebellar populations projecting to brainstem cardiovascular centers.
This high-resolution molecular mapping, integrated with detailed clinical phenotyping, aims to establish a mechanistic framework for understanding why some preterm infants are particularly vulnerable to SIDS, ultimately informing biomarker discovery and prevention strategies for this tragic outcome.