TARGET PROJECT 2
Specialized Pro-resolving Mediators (SPMs) in Children with Sickle Cell Disease (SCD).
Investigator: Robin Miller, M.D.
Mentor: Marie J. Stuart, M.D.
My primary role since my arrival at Nemours 18 years ago has been Director of the SCD Program at NAIDHC, which is the only pediatric SCD program in the state of Delaware. I have developed a multidisciplinary team providing comprehensive clinical care to more than 250 SCD patients and their families, and in recent years have worked to broaden our involvement in SCD research. Over the years our group has participated in a variety of research consortiums, pharmaceutical studies, investigator driven research projects and quality improvement initiatives. In 2014 our SCD program received NIH funding under the COBRE program (P20GM10921) to conduct clinical, psychosocial and basic research in SCD.
Since receiving that award, my focus has shifted almost exclusively to developing our center’s SCD clinical and research programs and serving as lead investigator on one of the COBRE target projects. Our endeavors to date have been highly successful and our patients are very engaged in the research. In addition, our team has developed and validated a standardized and robust workflow with custom analytics for guiding and tracking SCD care. This tool facilitates clinical communication between providers at the bedside, such as at critical transitions of care and also supports research efforts. Based on the 2014 NHLBI SCD guidelines, the platform is designed to enable quality improvement efforts build around individual deviations from population norms and population deviations from benchmarks and national guidelines.
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Co-Investigator: Yamaja Setty, Ph.D.
Dr. Setty received his doctoral in Biochemistry from Universy of Mysore in India and completed his post-doctoral fellowship at SUNY, Syracuse. His basic training in Lipid Biochemistry with a thesis devoted to the identification and biological roles of Prostaglandins in the silkworm. He continued his research interest transitioning from diabetes to sickle cell disease, clinical conditions with some pathologic similarities.
His current research interests include in vivo changes in (n-3) and (n-6) polyunsaturated fatty acids in children with sickle cell anemia, and the role of PS and heme as modulators of adhesion, inflammation and hemostasis. His extensive research experience and uniqueness of the present project i.e. availability of meticulously collected vaso-occlusive pain data and appropriately banked patient samples in this longitudinal infant toddler study is one in which I have a critical interest
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Project Summary:
Based on what is known about the pathophysiology of SCD, the demonstrated effects of the Omega-3 Fatty Acids (O3FAs) on leukocytes, the endothelium and inflammatory mediators, O3FAs may have great potential, by way of multiple mechanisms, to favorably impact the vaso-occlusive inflammatory pain complications in SCD. However, the optimal choice of O3FA or downstream mediator to develop as a therapy remains unclear.
In this study, we will measure DHA- and EPA- derived SPMs relevant to pain in children with SCD compared to African American controls using lipidomic assays, and evaluate their relationship to known biomarkers of inflammation and pain phenotype. We will stratify by age (less than 5, 6-12 and 12-20 years) based on the data by Setty et al. demonstrating that in children with SCD, the relative DHA and EPA deficiency in red cell phospholipids increases with age. Identifying specific perturbations in pro-resolving lipid mediators will contribute to the mechanistic understanding of chronic inflammation in SCD and may lead to the identification of novel therapeutic targets.