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. Anyigbo’s project is titled, “Socio-Contextual Influences of Infant and Early Childhood Mental Health”, and is mentored by Robert Ammerman, PhD, ABPP, Division of Behavioral Medicine & Clinical Psychology, Cincinnati Children’s Hospital Medical Center and Robert Kahn, MD, MPH, Division of General & Community Pediatrics, Cincinnati Children’s Hospital Medical Center. Dr. Chidiogo “Diogo” Anyigbo is a fellowship-trained academic pediatrician with a research agenda focused on identifying and mitigating the most critical social and environmental determinants of early adverse childhood mental health outcomes. Her long-term goal is to become an independently funded physician-investigator who partners with caregivers and interdisciplinary stakeholders (i.e., primary care clinicians, infant behavioral specialists, community experts, and managed care organizations) to implement evidence-based interventions to optimize behavioral in children under 5 years, thus promoting childhood mental health. This goal represents a longstanding personal and professional passion. This KL2 Research Scholars Career Development Program proposal aims to use electronic health record (EHR) data from pediatric primary care settings to identify early neighborhood and household social risk predictors of infant and early childhood behavioral functioning based on screenings completed by caregivers at routine well-child checks. The preliminary data will guide the design and feasibility testing of equitable household and neighborhood-based interventions to improve infant and early childhood behavioral health outcomes.

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 rich and diverse 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. Jose’s project is entitled, “Targeted drug delivery to limit luminal neutrophils in Clostridioides difficile infection (CDI)”, mentored by Rajat Madan, MD, PhD Division of Infectious Diseases, University of Cincinnati. Clostridioides difficile infection (CDI) is the leading cause of nosocomial infections in the U.S. It is classified as one of the top five organisms deemed to be an “urgent” public-health threat by the Centers for Disease Control and Prevention (CDC). The current treatment for acute CDI is to target the bacterium using antibiotics, often leaving the host inflammatory component of the disease unaddressed. While the initial driver of illness is C. difficile toxins, the host immune response contributes to the aggravation of the condition. In fact, the intensity of these host inflammatory responses is a better predictor of CDI outcomes than the pathogen burden. Thus, there is an urgent need to develop therapies to manage CDI-associated inflammation. Blood and tissue neutrophilia is a characteristic feature of the acute inflammatory response to CDI. Using a mouse model of CDI, Dr. Jose’s lab has identified that exaggerated host neutrophilia is a crucial driver of CDI-associated epithelial injury and disease severity. Dr. Jose and his team have also demonstrated that neutrophil mobilization to colonic tissue is driven by CXC chemokine receptor 2 (CXCR2). In this project, we propose developing a microencapsulated drug delivery system for the colonic delivery of CXCR2 inhibitors to prevent luminal recruitment of neutrophils and evaluate the delivered drug’s efficacy in reducing epithelial injury and disease severity. Findings from the study will improve the understanding of oral drug delivery to the colon during dysbiotic events and would provide the basis for independent funding to identify the potential of host-specific therapies in CDI.

Dr. Kotagal’s project is entitled, “Community-Engaged Approach to Addressing Child Injury”, mentored by Andrew Beck, MD, MPH, FAAP, Division of General & Community Pediatrics, Cincinnati Children’s Hospital Medical Center, Carley Riley, MD, MPP, MHS, Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, and Richard A. Falcone, Jr., MD, MPH, MMM, Division of Pediatric General & Thoracic Surgery, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine. As a pediatric trauma surgeon and equity researcher and advocate, Dr. Kotagal is committed to preventing childhood injury. Injury is the leading cause of childhood death and disability in the US. Moreover, this burden of disease is not equally distributed, with racial, ethnic, and socioeconomic inequities in child injury incidence and outcomes. These inequities suggest that broader contextual factors, such as the social determinants of health (SDH), drive injury frequency and severity. Therefore, the SDH represent targets for upstream, neighborhood interventions aimed at preventing injuries. Dr. Kotagal’s KL2 proposal seeks to understand community perspectives of injury, build a theory of improvement, and co-produce a response to child injury in one Cincinnati neighborhood. She will be using mixed methods to accomplish her aims, including use of semi-structured interviews and photovoice methodology as well as surveys to understand community perceptions of drivers of child injury. Building a community team, Dr. Kotagal and this team will then co-produce a theory of improvement and identify a set of interventions expected to reduce child injury in one Cincinnati neighborhood with disproportionately high injury rates. Through this KL2 proposal, Dr. Kotagal will build skills in complexity science and community-engaged research. This work will serve as the foundation for a K23 proposal focused on co-designing and testing interventions.

Dr. Phillip’s project is entitled, “Translational endotyping of chronic rhinosinusitis”, mentored by Dr. Gurjit Khurana Hershey, MD, PhD, Division of Asthma Research, Cincinnati Children’s Hospital Medical Center. 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.