The Jean and George Brumley Jr. Neonatal Perinatal Research Institute (NPRI)
The George and Jean Brumley, Jr. Neonatal-Perinatal Research Institute (NPRI) was created in 1996 as a multidisciplinary platform to address health problems of the newborn child through translational research programs and to train the next generation of physician-scientists to continue addressing these problems.
The NPRI aims to provide a dedicated environment wherein investigators from different fields can participate in collaborative multidisciplinary research aimed at understanding the basis of key problems suffered by neonates.
The NPRI was founded in 1996 by Dr. Ronald Goldberg, Chief of the Division of Neonatology, with the support of the late Dr. George Brumley, Jr., former Division Chief of the Duke Neonatal-Perinatal Program. The mission of the NPRI is to:
- explore the basis for birth defects and neonatal injury of the brain and lungs and translate the findings into clinical practice;
- address issues of health policy as they affect newborn care; and
- educate the next generation of physician-scientists to this endeavor.
Since it was founded, the NPRI has grown into a successful, multimillion dollar endeavor affiliated with 80 senior investigators, who are supported by a variety of external funding agencies.
The NPRI hosts a wide range of research initiatives by investigators with primary appointments in traditional departments including Cell Biology, Neurobiology, Nursing, Immunology, Pharmacology, Cardiology, Neonatology, Neurology, Pediatrics, Psychology, Maternal-Fetal Medicine, Anesthesiology, Critical Care Medicine, Medical Ethics, Genetics, Biomedical Engineering, Institute for Genome Sciences and Policy, Center for Human Genetics, Fuqua School of Business, the Duke Clinical Research Institute, and the Nicholas School of the Environment.
Topics under investigation can be categorized into three major groups: basic, clinical, and health care economics research. Basic research includes major initiatives in the causes of birth defects that particularly affect the cardio-craniofacial field and left-right cardiac axis determination, and the perinatal mechanisms of disrupted development and post-natal injury with special emphasis on lung, brain, and heart. Clinical research addresses the problems of low birth weight infants, morbidity and mortality, perinatal asphyxia, ventilatory management, growth and development of high-risk infants, and the role of genomics in neonatal morbidity. Research interests also include medical economics, and biomedical engineering--specifically in the areas of informatics, optics, virtual reality and microdigital fluidics.
- Birth Defects
Birth defects are the result of multifactorial causative agents, however, in recent years many congenital defects have been linked to genetic mutations. Research by NPRI investigators focuses on the role of genetic and cellular etiologies of birth defects that are the leading causes of infant mortality in the United States. Congenital malformations of the heart and neural tube are the most common serious birth defects and are the subject of intense investigation in the NPRI.
- Neonatal Brain and Lung Injury
A major interest of the NPRI is to elucidate basic mechanisms underlying brain development the stereotypical features of inflammation, injury, and repair that disrupt normal perinatal and neonatal development and the role of neural stem cells in development, injury and repair. The NPRI encourages skilled investigators with expertise in brain, lung, and cardiovascular injury to cooperate in the development and use of clinically relevant animal models, incorporating perinatal inflammation, oxidative and ischemic injury, and premature labor.
- Translational/Clinical Research
Clinical projects conducted under NPRI auspices include co-sponsoring of NICHD Neonatal Network research studies as well as Division of Neonatology research projects. The NPRI's success in clinical research was highlighted by the award of the first Duke Translational Medicine Award to NPRI investigators. Specific areas of interest include neonatal pulmonary hypertension, pulmonary injury, and lung function.
The Division has played a major role in developing the NICHD Neonatal Research Network DNA repository which is housed at Duke. This repository includes 1000 extremely low birth weight infants (<1000g) with generic data, one year neurodevelopmental follow-up and a one million SNP genome wide assay. In addition, Duke neonatology is studying the role of stem cell transfusion in hypoxic-ischemic encephalopathy and the use of microdigital fluidics and nanotechnology for bedside diagnosis.
NICHD-Sponsored Fellowship Training
A major aim of the NPRI is to train the next generation of clinical scientists. Our goal is to have an impact on the health of neonates by training leaders in scientific investigation (clinical as well as basic) in problems of the neonate. This is assured by the exceptionally talented basic and clinical mentors available to our trainees and the linking of the Duke Masters Programs in Genomics and Clinical Research, Bioinformatics and Health Policy to specific scientific research opportunities. The quality of the training program is reflected in the quality of its graduates and the NICHD Fellowship Training Grant awarded to the Division in 2005.
Intramural funding for the NPRI was initially provided by the Division of Neonatology and the Duke University Medical Center.
Extramural support comes from various sources including private donors. The NPRI secured substantial philanthropic research funding from outside the University such that its total current endowment is in excess of $4 million, ensuring ongoing stability of the program. Using these funds, the NPRI awards research and educational grants to fellows and junior faculty members to support multidisciplinary collaborations.
Funding to support individual investigators in the NPRI is through the National Institutes of Health, the Zeist Foundation, the Duke Endowment, and other private philanthropic organizations. Investigators in the NPRI from the Division of Neonatology have over $16 million in NIH funding.
The Zeist Foundation has endowed the Jean and George Brumley, Jr. Neonatal-Perinatal Research Institute, providing two endowed chairs for basic scientists and additional programatic support. The NPRI has been designated as a key program in the Dean's ten-year strategic research development plan.
NPRI lab space totals approximately 7,000 square feet.
NPRI-Affiliated Programs at Duke
- DUMC Mycology Research Unit (DUMRU)
The Duke Mycology Research Unit (DUMRU) and the Duke Antimicrobial Trials Unit (ATU) engages in translational research at the interface between basic science and clinical interventions. The ATU has collectively participated in over 20 clinical trials with antifungal agents over the past three years. These include pivotal trials and newer antifungal agents in adults and children. In addition, Duke has several outstanding clinician-scientists engaged in molecular fungal research including Gary M. Cox, MD, Aimee Zaas, MD, William Steinbach, MD, and Daniel Benjamin, MD, PhD, MPH, and Brian Smith, MD, who perform translational research in invasive mycoses in the pediatric and neonatal patient populations, respectively. DUMRU is supported by an NIH program grant to continue an interdisciplinary research approach to increase our understanding of the pathobiology of medically important fungi. Initially, this group received NPRI funding to develop nanotechnology fluidic approaches for the diagnosis of fungal sepsis and bacterial pneumonia with a focus on candidemia.
- Metabolomics/Biomarker Core
The Sarah W. Stedman Nutrition and Metabolism Center at Duke has developed a research-dedicated metabolomics biomarker laboratory. This laboratory was created by Christopher Newgard, PhD, and David Millington, PhD. Currently, the Stedman Center laboratory employs gas chromatography GC/MS and tandem MS to measure 100 "targeted" intermediary metabolites of known identity in four classes: a) free fatty acids, b) acyl carnitines, c) organic acids, and d) amino acids. The Stedman Center is in the process of expanding the capabilities of this targeted platform to include other analyte "modules," including phospholipids, sphingolipids, and a larger array of glucose-derived metabolites with an ultimate goal of creating a platform that provides targeted analysis of 300-400 individual metabolites. When complemented with the ability to measure key hormones of energy balance and metabolic hemostasis, pro- and anti-inflammatory cytokines and physiologic variables, this platform has the capacity to provide metabolic profiles that may allow insight into the broad impact of various intervention strategies.
- Duke Clinical Research Institute (DCRI)
The Duke Clinical Research Institute (DCRI) is the largest Academic Research Organization (ARO) in the world. The DCRI has received worldwide recognition for performing some of the largest and most influential clinical trials and outcome studies in medicine. The DCRI has over 800 employees, over 100 faculty, and 40 PhD and Master's level quantitative experts. This provides the DCRI with a significant ability to conduct research. The DCRI has a long history of cardiovascular research ranging from large-scale claims database analysis to clinical database analysis to large clinical trials. This effort is now being broadened to include multiple clinical disciplines. A primary objective of the DCRI is organizing collaborative clinical investigation and developing partnerships among centers, among disciplines, and among investigators to provide a more efficient methodology for performance and dissemination of research. Current large-scale trials involve more than 2,000 hospitals and practices in over 30 countries. The DCRI has played an important role in the translation of the collaborative basic research of Jonathan Stamler, MD and members of the Division of Neonatology, specifically, Ronald Goldberg, MD and Martin Moya, MD, a former fellow, to trial. Brian Smith, MD, a member of the Division of Neonatology, holds a faculty position in the DCRI.
- Duke Center for Human Genetics (CHG)
The Duke Center for Human Genetics has teamed with Neonatology faculty to develop the NRN's Anonymized DNA Bank and development of the genomic approach to neonatal disease. The CHG and its faculty are committed to the success of the NRN's efforts in Genomics. The CHG organizes its resources into two research cores: the Family Studies and Bioinformatics Core and the Genomics Resource Laboratory Core. CHG core-generated data is stored, integrated and analyzed using PEDIGENE ®, an internationally acclaimed CHG-designed computer data management system. As one of the largest and oldest academic DNA banks in the United States, the CHG DNA Bank and Tissue Repository is a cornerstone of our genomic research effort providing rapid, low cost, high quality DNA extraction and associated services to human genome researchers. Genotyping information from samples stored in the NRN bank will be directly entered into the NRN Coordinating Center's linked database. The Family Studies and Bioinformatics Core centralizes essential aspects of gene identification including Genetic Epidemiology, Family Ascertainment and Bioinformatics. The Genomics Resource Laboratory Core houses the CHG molecular biology unit. Here molecular biologists apply the latest genetic laboratory techniques to identify disease genes. The Genomics Research Laboratory posesses the technical and physical resources that support CHG research projects. These resources include 1) high-throughput genotyping, 2) mutation and polymorphism detection, 3) physical mapping and 4) sequencing and gene expression analysis. With its well-equipped and highly automated screening technology, this core conducts rapid sample isolation and analysis. The resulting data are managed and stored via the PEDIGENE® system. The Genomics Research Laboratory is home to the CHG DNA Bank and Tissue Repository which contains over 100,000 DNA samples from patients and families.
- Duke Institute for Genome Sciences and Policy
The Duke Institute for Genome Sciences and Policy (IGSP) consists of a multidisciplinary network of Centers and programs that together form an integrated approach to advancing the Genome Revolution and addressing its implications for health and society. Each of the following Centers provides core competencies and areas of scholarship that comprise the comprehensive scope of the IGSP's mission: 1) Center for Applied Genomics and Technology, 2) Center for Genome Ethics, Law, and Policy, 3) Center for Genomic Medicine, 4) Center for Bioinformatics and Computational Biology, 5) Center for Models of Human Disease, 6) Center for Population Genomics and Pharmacogenetics, and 7) Center for Evolutionary Genomics. While the IGSP is the major focal point on campus for the study of genome sciences and policy, it collaborates with other multidisciplinary research units at Duke doing related work in genomics. Duke Neonatology clinical research faculty have had its most direct interactions with the Center for Genomic Medicine and its Director, Geoffrey Ginsburg, MD, PhD. The Center's mission is to identify unique characteristics in both biospecimens and in the individual risk assessments that may define individual prognostic models and indicators of appropriate therapeutic interventions. It is dedicated to the development of clinico-genomic information that can be used for making medical decisions.
- Clinical Nanotechnology
The overall objective of this collaboration is to explore microfluidics for clinical blood reduction strategies. The Pratt School of Engineering and Advanced Liquid Logic Inc. are currently exploring the feasibility of an integrated microfluidic lab on-a-chip for fully automated clinical diagnostics on nanoliters of physiological samples. We will mainly focus on developing protocols and strategies for performing clinical chemistry and molecular diagnostics for point of care applications. Current diagnostic instruments are incapable of handling nanoliter sample volumes and are also unfit for performing the analysis in the field. Our long-term goal is to develop a portable, automated, and inexpensive platform for clinical diagnostics.