Pediatric brain tumors are the leading cause of brain tumor related death in children. Immunotherapy with altered cold sore virus (HSV) “G207” offers an innovative, targeted, less toxic therapy for pediatric brain tumors. G207 is unable to harm normal cells but can infect and kill tumor cells while also stimulating the patient’s own immune system to attack the tumor. In our recently completed Phase 1 pediatric trial of G207, the therapy was safe with evidence of dramatic responses and prolonged survival. While the results are very promising, we learned that to achieve even more long-term responses, we must develop combination therapies with G207. Our goal is to enhance this promising therapy substantially by developing a novel combination therapy that increases tumor cell killing and maintains the immune attack on the tumor. If safe and effective, we will advance the combination to clinical trials in children with brain tumor.

Brain injury sustained as a result of traumatic injury is extremely common in children and adults. As a result of the traumatic injury, it has been established that the normal blood clotting or coagulation mechanisms can be altered following trauma. This coagulopathy can lead to worsening brain injury and secondary injury to other organs. We have discovered that specific coagulation factors may play specific roles in the coagulation sequence following trauma and their alteration in levels can exacerbate secondary injury to these organs and alter the patient’s response to certain infections. We plan to clarify these exact mechanisms and evaluate whether restoration of specific coagulation factors may improve outcomes and response to injury/infection in mouse models of traumatic brain injury.

Social determinants of health (SDOH) are conditions in the environment where an individual is born, lives, learns, works and plays and that influence the individual’s health, functioning and quality of life. Living in poverty is one example of a SDOH that negatively impacts health. Adults with cancer who live in a persistent poverty community (poverty that persists over time) are more likely to die sooner than people who live elsewhere. Living in areas of high socioeconomic deprivation is another SDOH that is associated with premature cancer death even when the patients are receiving the best treatments. Further, among black adults with cancer, increasing residential segregation is associated with declining cancer outcomes. The vast majority of children with cancer are now cured due to advances in treatment and supportive care. However, these improvements are not shared equally by all children. This study examines the role of SDOH, including persistent child poverty, to learn how these factors impact childhood cancer outcomes.

Cystic Fibrosis (CF) is one of the most common genetic diseases in the world leading to lower life expectancy. People with CF often have long term infections in the lung with bacteria, causing difficulty breathing and inflammation. The mold Aspergillus fumigatus is more of a fungus that we often see in CF lungs, and is seen in complex lung conditions in this population. However, we don’t know much about this and this mold seems to be associated with a bacteria Pseudomonas aeruginosa that is common in CF, but is known to have long term lung damage. Given this, we need to understand more about what Aspergillus fumigatus is telling us and what it is associated with. To do this, we will use CF cells and a CF rat to mimic these two infections. People with CF have very thick mucus that may allow this mold to grow. Given that, we will also stimulate the cells to make more CF mucus to see if this helps promote mold growth. In both of these experiments, we will try and treat the Pseudomonas aeruginosa to see if it has lasting effects that make the mold grow. At the end of the experiment, we will see how much mold and bacteria have grown, what inflammation they have triggered, and how they have damaged the lungs. By doing this, we will better understand how Aspergillus fumigatus affects people with CF and can hopefully develop new screening and treatment guidelines when pairing this with clinical experiments.

This innovative project will develop machine learning based predictive models to accurately predict adverse outcomes (death or moderate/severe neurodevelopmental disability) in infants who have hypoxic-ischemic encephalopathy (HIE) at birth. Infants with HIE are at a high risk of adverse outcomes and earlier identification of the risk by the proposed project may help in better management and improvements of outcomes in such infants.

Blood or marrow transplantation (BMT) is being increasingly used as curative therapy for many cancers and blood disorders among children. However, children who receive a BMT experience many side effects, some of which can lead to death. Currently, our understanding of who will experience these serious side effects is limited. We are proposing a study to assess how body composition (muscle and fat mass) before BMT measured using CT-scans affects early side effects after BMT and deaths from complications due to treatment at 1-year after BMT. It is possible that children who receive same doses of chemotherapy (based on weight) have differing biodistribution of drugs (due to variations in body composition) which could explain the differences in outcomes. We will also test this hypothesis in a subgroup of patients who receive a drug called busulfan by assessing how pre-BMT body composition influences levels of this drug among patients.

This proposal will provide standardization of care for neonates who develop severe AKI after undergoing cardiac surgery by proving that early initiation of dialysis is beneficial and improves outcomes. This proposal will also assist with the timing to effectively discontinue dialysis. This is beneficial because performing dialysis is not without risks, such as infection. The findings from this proposal will help reduce some of the complications associated with AKI that will not only be beneficial to the patients but also has a large economic impact on the healthcare system by reducing healthcare cost, complications and duration of hospitalization.