The division has an unwavering commitment to foster basic, translational, and clinical research.
Wet laboratory space is located in the Academic Research Building, Human Development Building, Brain Institute, and the Dental Sciences Building. Divisional faculty are involved in cutting-edge research related to enteral nutrition, microbiome and prematurity, necrotizing enterocolitis, hypoxia ischemic encephalopathy, nitric oxide and oxidative stress, health care economics, breastfeeding and lactation, neonatal sepsis and inflammatory biology, medical ethics, developmental follow-up, and clinical trials. The divisional research program is supported by grants and contracts from a variety of agencies including the National Institutes of Health, American Heart Association, March of Dimes, Thrasher Fund, and private industry.
The Wynn Laboratory is focused on the investigation of neonatal-specific innate immune cellular function and inflammatory signaling during sepsis as well as development of novel therapeutic immunomodulatory strategies aimed at improving sepsis outcomes.
The purpose of this study is to create a detailed medical and sample database of infants born with HIE.
This project will examine the safety and dosing of enteral melatonin in infants with HI undergoing hypothermia. The phase 0/1 study will examine the pharmacodynamics, pharmacokinetics, and safety and effectiveness of enterally-administered melatonin in reducing oxidative stress and the inflammatory cascade in neonates undergoing hypothermia. In addition, outcomes at 18-22 months will be performed. The study will be carried out in the Florida Neonatal Neurologic Network, which the PI founded.
Understanding and diagnosing sepsis is currently difficult because the extremely small blood volume in the premature newborn limits both our diagnostic and research approaches. Using innovative microfluidic technologies focused on innate immune function and the most commonly used clinical diagnostics, we propose a paradigm-changing approach to identifying sepsis and its underlying causes in premature newborns at risk of sepsis.
In this proposal, we examine a new pathway that leads to organ injury in neonatal sepsis observed in two distinct organ systems (the lung and gut), and identify both the responsible cell populations and the local mediators that regulate this tissue injury. These studies will provide a strong theoretical foundation for novel clinical interventions in neonatal sepsis.
In contrast to sepsis definitions in adults and children, definitions of sepsis commonly used in neonatology are variable and heavily predicated on the isolation of pathogens from blood and/or the associated length of prescribed antimicrobial treatment. Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The presence of life-threatening organ dysfunction is demonstrated using a sequential organ failure assessment (SOFA) to determine risk of ICU admission or mortality. To define sepsis in neonates therefore requires an operational definition of organ dysfunction applicable specifically to this population (neonatal SOFA; nSOFA) that predicts mortality in the setting of presumed infection. We recently showed the progression of organ failure in neonates with lethal LOS in a large retrospective cohort (2016). Guided by those data, we developed and tested an objective, electronic health record (EHR)-automated, nSOFA scoring system to predict mortality from LOS in premature, very low birth weight infants (2019).
Inhalational gases are attractive to the bedside clinician caring for neonates with HIE because they have minimal side effects and can be easily titrated and rapidly stopped if side effects develop. Three potential inhalational agents that could act synergistically with hypothermia are carbon monoxide (CO), inhaled nitric oxide (iNO) and helium. Studies during the last decade have demonstrated that inert gases may be promising therapies following HI injury. The Xenon gas been the most promising inhaled gas to date, however the translational utility is limited by cost. Our long-term goal is to utilize inhalational gases as a therapy for neonates with HIE.
This multi-center project combines Single Molecule Arrays with noninvasive salivary diagnostics to integrate the first comprehensive, ultra-sensitive multiplexed salivary infection-screening platform into neonatal care. The salivary protein expression levels of multiple biomarkers will be assessed in over 4000 newborns undergoing a rule out sepsis evaluation in NICUs at Tufts University, Brown University, and UF Heath. Data will be used to develop and validate a predictive model of neonatal infection, establish normative reference ranges of each inflammatory biomarker across varying gestational ages, sex, and weights, and assess the potential of these biomarkers to predict other neonatal morbidities associated with an inflammatory response.