PROJECT SUMMARY Andrew Heitzer, PhD, is an Assistant Member in the Psychology and Biobehavioral Sciences Department at St. Jude Children’s Research Hospital. The overall goal of this K23 proposal is the development of Dr. Heitzer into an independent investigator focused on implementing behavioral interventions to improve neurocognitive and academic outcomes in patients diagnosed with sickle cell disease (SCD). Dr. Heitzer has organized a mentorship team with distinguished records of NIH funding who are committed to advancing his career. Mentors have expertise in dissemination and implementation science, intervention adaptation and development, mixed-methods research, and conduct of behavioral clinical trials in SCD. SCD is a genetic disorder of hemoglobin characterized by early and progressive neurocognitive dysfunction affecting 100,000 individuals in the United States. Pervasive neurocognitive difficulties significantly contribute to poor academic performance in mathematics, reading, and writing. A critical gap exists in developing evidence-based interventions to address the substantial functional consequences of cognitive deficits in SCD. Attempts to address neurocognitive deficits in SCD through behavioral approaches have struggled with adherence, limiting their effectiveness. Addressing barriers to adherence and increasing accessibility is critical to intervention success. This is particularly true for patients with SCD, who are predominately racial minorities from underserved communities. These families are less likely to report developmental concerns, experience more significant stigma for seeking help, and underutilize early intervention services for children with developmental delays. Behavioral interventions early in life can potentially prevent later neurodevelopmental and academic deficits. Specifically, interventions that target school readiness skills, including early literacy, numeracy, and self-regulation, produce lasting improvements in attention, working memory, and academic performance. Although several evidence-based school readiness interventions exist, they have not considered the contextual factors unique to patients with SCD. The specific aims are: 1) Adapt a behavioral intervention to improve school readiness for preschoolers with SCD; 2) Conduct a pilot trial of the adapted school readiness intervention compared to routine care to assess feasibility, acceptability, and preliminary efficacy. This will be the first study to adapt and test an intervention approach fitted for patients with SCD, facilitating the development of targeted interventions with great potential for improving the quality of life for all children living with SCD. Data collected from the pilot trial will provide the foundation to apply for an R01-funded study to test the intervention’s efficacy facilitated by an ongoing multi-site longitudinal cohort study led by St. Jude.