Dr. Anukanth’s project is titled, “Assessing the role of feeder cells in NK cell priming”, mentored by John Byrd, MD, Trisha Wise-Draper, MD, PhD, Division of Hematology-Oncology, University of Cincinnati, and Stephen Waggoner, PhD, Division of Human Genetics, Cincinnati Children’s Hospital Medical Center. Cell therapy such as chimeric antigen receptor (CAR) T-cell therapy is one of the newest treatments available to treat aggressive blood cancers. However, there are a few major barriers to using these T-cell therapies including serious side effects and difficulty collecting sufficient T-cells from patients undergoing intensive chemotherapy. Another type of cell therapy uses natural killer (NK) cells. NK cells are unique in that they can be isolated from the blood of healthy unrelated donors, stored, and then safely given to patients when needed (meaning stocks of “off-the-shelf” donor NK cells can be made ahead of time and be ready to use). However, NK cells constitute a small percentage of circulating cells in the blood. Therefore, robust NK cell expansion after isolation from peripheral blood is required to generate clinically appropriate doses of NK cells. While there is no standardized method of NK cell expansion, most clinical trials use genetically modified versions of the same feeder cell line to expand NK cells regardless of the target tumor. Dr. Anukanth’s work shows that NK cells from the same donor expanded using different types of feeder cells have differing ability to recognize and kill tumor cells. Her proposal seeks to understand the mechanism underlying this difference in NK cell cytotoxic efficacy. We hypothesize that growing NK cells with disease-specific feeder cells will enhance their efficacy to kill specific tumor types. Improving the process of NK cell expansion will ultimately lead to safer and more effective cell therapy options than are currently available.

Dr. Caldwell’s project is entitled, “Kidney Transplant Rejection-Induced Allograft Damage Signatures”, mentored by David Hildeman, PhD, Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, E. Steve Woodle, MD, Department of Surgery, University of Cincinnati, and David Hooper, MD, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center. Kidney transplantation is a life saving treatment of end-stage kidney disease, but the survival of transplanted kidneys is limited by rejection. As most work on allograft rejection has focused on characterizing the inflammatory infiltrate, the graft response to rejection remains largely uncharacterized. Understanding the parenchymal response to rejection may enhance our diagnosis and treatment of rejection. In this study we will utilize single-cell RNA sequencing of either kidney allograft biopsy samples or urinary sediment taken at time of rejection or during its treatment to define the allograft transcriptomic response to rejection and signatures of either recovery or failed repair. In doing so we aim to identify markers that will enhance the diagnostic and prognostic yield of kidney allograft biopsy as well as possible noninvasive urinary markers of rejection and recovery.

Dr. El Rouby’s project is entitled, “Unlocking the risk of Metabolic Syndrome (MetS) post antipsychotics in pediatrics”, mentored by Melissa DelBello, MD, Jeffrey Strawn, MD, Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati, and Lisa Martin, PhD, Division of Human Genetics, Cincinnati Children’s Hospital Medical Center. Second-generation antipsychotics are widely used in pediatrics and youth posing a significant risk of metabolic syndrome in approximately 40-60% of the pediatric population, which can lead to type 2 diabetes and cardiovascular complications. In the KL2 project, I will utilize the electronic health records such as the electronics medical records and genomics network (eMERGE) to define the prevalence of second-generation antipsychotics-induced Metabolic Syndrome (SGA-MetS) in pediatric and youth populations. Further, I will investigate the ability of polygenic risk scores (PRS) to predict SGA-MetS. The long-term aim of this project is to integrate clinical and polygenic risk scores in the clinic to identify high-risk patients at the outset of treatment, enabling early interventions.

Dr. Morin's project is entitled, "Prostate-specific membrane antigen (PSMA) PET/CT in pediatric liver tumors". Liver tumors are rare in children, but those with advanced, unresectable, or relapsed disease face limited treatment options and poor outcomes. Current diagnostic tools cannot reliably predict treatment response or risk of recurrence. This study will investigate a novel diagnostic—and potential therapeutic—approach for pediatric liver tumors using a prostate-specific membrane antigen (PSMA) imaging agent. By repurposing PSMA-targeted theranostics, which are already transforming adult oncology, this research aims to improve diagnostic accuracy and prognostication with PSMA-PET and lay the foundation for targeted therapies in children with advanced disease.

Dr. Myers's project is entitled, "The sociomedical and financial context of pediatric intensive care utilization". Through this proposal, we will investigate how neighborhood-level factors contribute to pediatric intensive care unit (PICU) utilization and outcomes. By examining both markers of community deprivation and resilience, the study aims to inform the development of neighborhood-based and hospital-level interventions to reduce health and economic disparities. Ultimately, this work seeks to improve outcomes for all children and reduce the financial burdens of pediatric critical illness on families and communities.

Dr. Phillip’s project is entitled, "Translational endotyping of chronic rhinosinusitis", mentored by Dr. Gurjit Khurana Hershey, MD, PhD, Division of Pulmonary, Cincinnati Children’s Hospital. Dr. Phillip’s will utilize next generation sequencing to endotype inflammatory profiles of patients with chronic rhinosinusitis with nasal polyps to provide more targeted and efficient therapeutic interventions for these patients. From this data will explore non-invasively obtained biomarkers to predict treatment response and improve patient outcomes.

Dr. Udoko’s project is entitled, “Optimizing Collaboration and Coordination to Improve Outcomes in Pediatric Asthma”, mentored by Michael Seid, PhD and Ellen Lipstein, MD, MPH, James M. Anderson Center for Health Systems Excellence, Cincinnati Children’s Hospital Medical Center. Pediatric asthma displays stark inequities in morbidity and mortality driven by social determinants of health (SDOH). Despite increased SDOH screening and referrals, barriers to referral enrollment persist, suggesting the need for a deeper understanding of the drivers for engagement and care coordination in SDOH processes. Engaging and integrating multiple stakeholder perspectives through co-production is a promising avenue for identifying new strategies to improve caregiver collaboration in SDOH processes. We need a system that connects community and hospital-based care settings to a) identify families' needs, b) co-produce a plan to address them, and c) execute that plan to match resources to families' needs and coordinate care. This project aims to improve collaboration and coordination surrounding SDOH needs and care gaps in asthma by: 1) establishing a framework for caregiver collaboration in SDOH plans. 2) identifying critical facilitators for multi-level community implementation of SDOH plans in the setting of CHWs and school community partnerships. These findings will be the foundation for future design and implementation of system-level interventions to improve the receipt of resources for SDOH needs, facilitate comprehensive asthma care, and improve clinical outcomes. Such interventions are pivotal in eliminating disparities in asthma and improving population health.

Zandvakili's project is entitled, "GLP1 Receptor Agonist Associations with Adverse Endoscopy and Anesthesia Outcomes". Dr. Zandvakili aims to reduce unnecessary burdens for patients who need endoscopies such as screening colonoscopies for colorectal cancer. Recently, there have been concerns that the “GLP-1 receptor agonist” class of medications, now used widely for weight loss and diabetes treatment, may pose risks during endoscopy because these medications are known to slow the gastrointestinal tract. These risks include anesthesia safety risks such as pulmonary aspiration food that remains in stomach despite fasting for procedures, or risk to endoscopy quality such as poor colonoscopy bowel preparation. There has been much uncertainty about whether theoretical risks are founded, causing delays in care and cancellations in procedures due to recommendations to hold these medications before endoscopy. Dr Zandvakili aims to determine if concerns surrounding anesthesia safety and negative impacts on endoscopy are warranted. This proposals aims to answer these questions in one of two ways: First by analyzing large clinical databases containing de-identified patient data to look for safety risks such as diagnosis of pulmonary aspiration occurring after endoscopy. And second, using computer algorithms to analyze thousands of de-identified patient endoscopy encounters at UC Health to search for instances of adverse anesthesia events or endoscopy outcomes.