Scientific Faculty and Collaborators
Overview:
The NPRI (Neonatal-Perinatal Research Institute) at Duke University was started in 1996 under the direction of Ronald Goldberg, M.D., Division Chief, in order to promote interdisciplinary research initailly related to the prevention and treatment of cellular injury in the lung and brain. Although great strides have been made in the care of sick newborns, chronic lung injury and brain injuries are still challenges in the smallest premature babies. The NPRI draws on the expertise of physicians and scientists across Duke University & Medical Campus.
The program faculty have been divided into mentors who are senior investigators with a past record of outstanding productivity and training, and associate mentors who have less experience but are actively involved in research and program development and thus can give technical assistance and act as role models. The mentors include MD and PhD faculty who are members of the Neonatal-Perinatal Research Institute.
Program Faculty:
The research interests of each Mentor and Associate Mentor are described below in the context of the track that they support. Research support for each faculty member is included. Basic research focuses on areas of investigation: 1) Developmental Biology, 2) Neonatal Lung Development and Repair; 3) Neural Injury and Repair in the Fetus and Neonate 4) Clinical research involves clinical investigation which will be done locally as well as via the NICHD Neonatal Research Network 5) Genomic Research which involves the division of Neonatology, the Center for Human Genetics, Institute for Genomics (IGSP)and the NICHD Neonatal Research Network.
Track I : Basic Research
The discoveries found in basic science laboratories provide the basis of future therapies. Our basic science research track trains fellows in the scientific method and provides hands-on experience in hypothesis-testing research. Opportunities for basic research are offered below.
Birth defects and low birth weight are significant problems in the neonate that frequently require intensive clinical care. Infant mortality from these problems is very high. The consequences extend to the entire life of the afflicted individual and affect not only the immediate family but society at large because of the loss of human productivity and the expense of clinical care for these individuals. It is of vital importance to discover the causes and consequences of the clinical conditions and treatment to alleviate the long-term impact of these problems.
The Neonatal-Perinatal Research Institute (NPRI) includes basic research into the etiology and pathogenesis of birth defects, and prenatal and neonatal injury in a variety of animal models; clinical research focuses on the causes of neonatal brain and lung injury and their sequellae in later childhood; and finally, research in health policy, health economics and medical informatics aims to discover and surmount barriers to appropriate medical care for affected patients and their families.
The educational mission of the NPRI is directed at creating academic leaders in research and translational medicine directed specifically to neonatal well-being.
The environment for research in Developmental Biology is particularly rich on the Duke campus. Research opportunities range from stem cell biology to studying genomics and proteomics in transgenic zebrafish and mice. Fellows have the opportunity to learn a diverse array of molecular and cellular techniques including physiological functional studies at the whole animal or organ level as well as in single cells.
Page A. W. Anderson, M.D., Professor and Vice Chair of Research
Dr. Anderson is interested in mechanisms involved in maturation of heart and cardiovascular function. These include control of cytosolic calcium concentration and sarcomere dynamics in isolated ventricular myocytes, the expression of thin filament regulatory proteins and the functional significance of heterogeneity in isoform expression, regulation of myofilament sensitivity to calcium concentration, and the relationships between the expression of membrane proteins that control cell calcium and the contractile proteins that respond to changes in cell calcium. His laboratory discovered that a complement inhibitor, soluble complement receptor-l, palliates the post cardiopulmonary bypass syndrome in neonatal pigs which has led to a Phase IM trial in infants undergoing cardiac surgery requiring cardiopulmonary bypass.
Dr. Page A. W. Anderson, Professor of Pediatrics, Vice Chair for Research, has a broad-based research program that studies cardiac myofilament proteins, the pathobiology of heart disease, and stem cell differentiation in the heart. The recognition of Dr. Anderson's scientific program is evidenced by his being funded continuously by the NIH since 1978, his being named Chair of the NHLBI study section, Cardiovascular A, and his participation and membership in multiple other NIH review groups.
His investigation of complement activation and its role in the inflammatory post-cardiopulmonary bypass syndrome includes studies in the animal and in the infant. His demonstration that blockade of the complement cascades is protective of myofilament, cardiac, and lung function in the neonatal pig led to a phase I/II trial in infants, that yielded results that were consistent with the neonatal pig studies. Subsequent pre-clinical studies of modulating complement activation in the neonatal animal have further supported the role of complement activation in the post-cardiopulmonary bypass syndrome. The ultimate aim is to use these pre-clinical studies to support the performance of Phase II trials in the infant undergoing cardiopulmonary bypass.
His studies of cardiac protein isoform expression focus on cardiac troponin T, essential in cardiac contraction. His laboratory was the first to identify in the human and in other species multiple isoforms of cardiac troponin T and to demonstrate a correlation between myofibrillar ATPase activity and troponin T isoform expression in myocardium from the normal and failing human heart. These functional results were supported by his subsequent study in the infant. His laboratory is presently studying the consequences of transgenic expression of these isoforms in experiments that study the healthy and cardiomyopathic heart and that range from the single cell to the intact animal.
His laboratory in collaboration with Dr. Peggy Kirby of Duke University and Dr. Nadia Malouf at the University of North Carolina at Chapel Hill is using a clonal stem cell line, derived from an adult animal, to study engraftment and differentiation. They have demonstrated that these clonal cells differentiate into endothelial cells and myocytes in mouse and rat heart in vivo and are incorporated into the chick embryo. The ongoing studies are focusing on the biology of engraftment and differentiation and the consequences of these processes on embryogenesis and organ function in the normal animal and animal models of human diseases.
Dr. Anderson is the Principal Investigator of the Duke Clinical Center in the NHLBI funded Pediatric Heart Disease Network. The multi-Center network has and is carrying out clinical trials that range from the treatment of the pediatric patient with a functional single ventricle to the patient with
Kawasaki 's disease. Dr. Anderson, in collaboration with Dr. Jennifer Li, and other members of the Network design and carry out these clinical trials.
Altogether this diverse and rich clinical and basic science research program that incorporates molecular and cell biology, physiology, and pathology will provide strong research experiences for the trainee.
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Blanche Capel, Ph.D., Professor Cell Biology
Dr. Capel 's work explores the role of Sry in organogenesis of the testis. During development, specific genes are thought to act as genetic switches, inducing molecular cascades that control the differentiation of embryonic tissues into adult cell types and organs. The process of sex determination in mammals is dependent on the expression of a single gene on the Y chromosome, Sry. Sry acts as a genetic switch and induces a wide variety of downstream events in the undifferentiated gonad to turn its development from the ovarian pathway to the testis. Her laboratory studies the cellular and molecular events induced by Sry expression to give us information about genetic switch genes, testis formation and organ development in general. Her lab has identified several pathways downstream of Sry , including cell migration, cell differentiation, proliferation, and many of the genes associated with these events. Experimental approaches include organ culture, transgenic mice, differential screens, confocal microscopy, biochemical and molecular techniques, classic mouse genetics and comparative embryology.
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Brigid L.M. Hogan, PhD, FRS, Professor and Chairman of Cell Biology
A major focus of the Hogan lab is on the basic mechanisms controlling the development of the lung. Projects include the identification of transcription factors and signaling pathways controlling lung epithelial and mesenchymal call growth and differentiation. Typical questions are what controls the maintenance of a population of undifferentiated progenitor epithelial cells in the distal lung, what factors control their allocation to different cell fates and what determines their timing of differentiation into alveolar precursors? To achieve this goal, the lab is developing a wide variety of transgenic and conditional gene knockout mouse models. In addition, cell culture techniques are being exploited to follow the behavior of mutant and wild type cells and to observe cell fate using lineage markers. The principles involved in lung development are the same as for many other organs that develop by branching morphogenesis, including kidney, submandibular gland, mammary gland and teeth. The environment and training is therefore very suitable for long term studies in all aspects of organogenesis. As well as studying normal lung development, the Hogan lab is exploring a number of experimental injury models (e.g., exposure of adult mice to sulfur dioxide) to understand the basic processes of lung repair and regeneration. Typical questions are what cells proliferate after injury and do they undergo dedifferentiation and switching in cell fate? What are the roles of inflammation and host immunity in repair and regeneration after injury? Another project in the Hogan lab involves the basic mechanisms underlying the growth and development of tracheal submucosal glands and palatine and lingual mucous and serous glands. Submucosal glands undergo hypertrophy in a number of diseases, including severe asthma, but little is known about the cell biology and genetics of their development. Finally, studies are underway to differentiate mouse embryonic stem (ES) cells into endoderm tissues, including lung and pancreas. The long term goal of these efforts is to use the endodermal cells for transplantation and organ repair.
Dr. Hogan is exploring the molecular, cellular and genetic mechanisms regulating the growth, differentiation, and homeostasis of mammalian organ systems. Her lab uses the mouse as a model organism for embryological and genetic manipulation. Currently, her group is focusing on the early branching morphogenesis and postnatal turnover and repair of the lungs and other endodermal organs.
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Salim Idriss , M.D. , Ph.D., Assistant Professor, Pediatrics, Cardiology
I am primarily interested in the effects of age and development on cardiac electrical stability. The electrical properties of the myocardium continue to develop and mature after birth. These changes may affect susceptibility to malignant arrhythmias at different ages. I am investigating these changes at the tissue level in collaboration with faculty in Biomedical Engineering, Mathematics, and Physics. I have a second interest in real-time three-dimensional echocardiography for visualization and guidance of interventional electrophysiologic procedures.
His research focuses on understanding postnatal development of the electrophysiologic properties of ventricular myocardium. Specifically, he is studying age-related changes in the action potential across the ventricular wall using various techniques including intracellular microelectrode and optical records. Studies are performed to evaluate not only the steady-state electrophysiologic properties but dynamic action potential kinetics as well. This information will allow us to better understand the complex interaction between myocardial development and age-related changes in arrhythmia vulnerability.
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Joseph Izatt, Ph.D., Associate Professor, Department of Biomedical Engineering
Associate Professor of Biomedical Engineering, Associate Professor in Ophthalmology. Izatt's research interest include biomedical optics, spectroscopy, and imaging; laser-tissue interactions; optical and ultrasonic signal processing; novel methods for high-resolution, and minimally invasive medical imaging and tissue characterization. Biophotonics is concerned with the application of cutting-edge optoelectronic technologies to problems in the biomedical sciences. My research centers on the application of optical technologies for non-invasive, high-resolution imaging and sensing in living biological tissues. The technologies we use in my laboratory include acousto-optic and integrated-optic devices, femtosecond lasers, and ultrabroadband fiber optic telecommunications equipment. The applications of the systems we build include noninvasive medical diagnostics, in-vivo tomographic microscopes, and high-throughput three-dimensional small animal imaging systems for genomics studies. Our work involves multiple collaborations with engineers, biologists, and physicians at Duke and elsewhere.
Dr. Izatt’s research concentrates on optical coherence tomography (OCT) and its applications to biomedical imaging. OCT allows subsurface imaging at the micron level using light, with present applications to developmental biology models and human clinical imaging. Collaboration with Dr. Margaret Kirby has allowed three dimensional imaging of cardiac morphology and development in the chick embryo. Human clinical research is actively ongoing including ophthalmologic applications of OCT in retinal imaging and gastrointestinal endoscopic imaging utilizing OCT. New research is focusing on the development of molecular contrasts to complement OCT imaging. Dr. Izatt serves as Director of the Laboratory for Biophotonics at the Fitzpatrick Center for Photonics and Communications Systems at Duke University.
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Margaret Kirby, Ph.D., Cardiac and Brain Morphogenesis
Dr. Kirby is interested in development of the heart and in congenital defects of the heart that involve head and face development. She established the cardiac neural crest model of congenital heart defects over 20 years ago and has continued elucidating the functional and structural implications of this model. She has recently described a secondary heart field that produces the conotruncal myocardium and has found that cardiac neural crest is necessary for normal generation of this myocardium via its regulation of growth factor availability in the caudal pharynx. She has also recently described a new ventral organizer of the head, face and heart that may be a key to congenital sequences of defects.
Dr. Margaret Kirby , Professor of Pediatrics (Neonatology), Cell Biology and Biology is internationally recognized for her studies of cardiac development. Dr. Kirby and her research team were recruited to the Department of Pediatrics in the Spring of 2001. She has as a member of multiple editorial boards, including those of the Developmental Dynamics, Circulation, Circulation Research, Embryo Today. Her service on NIH review committees includes being a member of the Program Project Review Committee A of NHLBI. And the Cardiovascular Development study section.
Dr. Kirby proposed and tested the hypothesis that neural crest cell function is essential for normal structural and functional development of the heart and great arteries. She established this neural crest cell model as the first proven experimental model to explain congenital cardiac malformations. Her laboratory demonstrated that cardiovascular, thymus, and parathyroid development depend on the migration and incorporation of neural crest cells into these structures. In the context of ventricular dysrhythmias in patients with congenital cardiac defects, her laboratory has also documented that myocardial excitation-contraction coupling is impaired in the embryonic heart in the absence of neural crest cells. The establishment of the neural crest cell model in chick embryos has led to it being the gold standard in analyzing the phenotype of transgenic and mutant mice with defective heart development.
Recently, Dr. Kirby has developed a modification of her neural crest cell theory based on the presence of a midline stripe that is an organizer for brain, face, and heart development. This model provides a unifying concept for commonly recognized clinical syndromes in which abnormal midface, neural, and heart development are present. In addition, her lab has identified a special field of cells in the cardiogenic mesoderm that forms the arterial pole of the heart. These cells are at particular risk for abnormal development which results in many of the most common conotruncal malformations seen in children.The goal of her research is to establish the mechanisms of signal coordination by neural crest cells in the pharynx and to determine the factors that alter neural crest cell migration and function. These signals are required for arterial pole development. The recently described cells that form the arterial pole depend upon these signals in providing definitive myocardium to the arterial pole. Her laboratory will provide the trainees a rich basic science research environment in the molecular and cell biology study of the mechanisms underlying normal embryonic development.
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John Klingensmith, Ph.D., Cell Biology
Dr. Klingensmith is interested in how the mammalian body plan is generated during early pregnancy and is seeking to understand the mechanisms that establish and pattern the body axes and organ precursors of the embryo. He uses genetic technologies available in the mouse to study induction, pattern formation, and morphogenesis, particularly of the neural tube and surrounding axial skeleton. Projects underway focus primarily on the role of molecules initially identified as important embryonic organizer genes that encode the activities of Spemann's organizer. These organizer genes have essential roles in development of specific organs and structures arising later in embryogenesis, including the forebrain, the craniofacial skeleton, and the heart. Ongoing work on early axial patterning has led to insights into the etiology of clinically important congenital malformations. He is also funded to study the role of hedgehog signaling in heart morphogenesis and to identify key downstream genes.
Dr. Klingensmith is an Assistant Professor of Cell Biology at Duke University Medical Center. His graduate training was in genetics at Harvard and in developmental biology at Stanford, and his postdoctoral work was in mammalian embryology at Toronto. He has been an independent investigator at Duke since January 1998. He holds two NIH grants, one on craniofacial development and the other on neural tube development. He is a prominent educator in the Department of Cell Biology for graduate students in developmental biology and genetics. He also teaches a laboratory course to first year medical students at Duke University Medical School. Dr. Klingensmith has served on several graduate admissions committees and faculty search committees, and is a peer reviewer of grants and manuscripts . However, his primary work is basic research in mammalian development and birth defects, for which he received a Presidential Early Career Award (PECASE) from President Bush at the White House in July, 2002. Dr. Klingensmith’s lab will provide an excellent basic research opportunity for study of the relationship between brain and heart development. The interactions between Dr. Klingensmith and Dr's. Kirby and Creazzo will facilitate and expand the breadth of research opportunities possible.
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David R. McClay , Ph.D. , Professor of Zoology. Developmental, Cell and Molecular Biology
Dr. McClay 's research is focused on morphogenesis, cell signaling, and cell adhesion. As the embryo establishes three germ layers and organizes the basic body plan, cells rearrange in highly predictable ways. His lab studies 1) the mechanisms by which cells are specified during cleavage to become mesoderm or endoderm; 2) the mechanisms employed by cells to morphogenetically rearrange during gastrulation; and 3) the function of several specific proteins in the morphogenetic process. These functions include participation in cell adhesion, morphogenetic boundary formation and acquisition of positional information during embryogenesis.
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ii. Developmental Endocrinology
Michael Freemark , MD , Professor of Pediatrics (Endocrinology and Diabetes)
Dr. Freemark's work has focused on the roles of the lactogenic hormones in perinatal and postnatal insulin production. He has made the novel observation that PRLRs in the human fetus and fetal rat are expressed only in pancreatic exocrine tissue and ductal epithelial cells in early gestation, emerging in pancreatic beta cells near the time of birth. Since the emergence of PRLRs in pancreatic beta cells coincides with a surge of beta cell proliferation and insulin production, he hypothesized that lactogens might play roles in islet maturation. Subsequent studies lent strong support to this hypothesis. The lactogenic and somatogenic hormones have overlapping actions in a number of metabolic systems. Consequently, some effects of lactogen resistance might be obscured by compensatory actions of growth hormone. To address this problem, his laboratory has recently generated a mouse with combined deficiencies in lactogen signaling and GH production. This mouse is unique among experimental models of somatolactogen production and action. The model was created by breeding prolactin receptor (PRLR)-deficient (knockout) males with GH-deficient ("little") females. In contrast to mice with isolated GH- or PRLR-deficiencies, double mutant (lactogen-resistant and GH-deficient) mice on day 7 of life had growth failure and hypoglycemia These findings suggest that lactogens and GH act in concert to facilitate weight gain and glucose homeostasis during the perinatal period. Plasma insulin, IGF-I and IGF-H concentrations were decreased in both GH-deficient and double-mutant neonates but were normal in PRLR-deficient mice. Body weights of the double mutants were decreased markedly during the first 3-4 months of age, and adults had striking reductions in femur length, plasma IGF-I and IGF binding protein-3 concentrations, and femoral bone mineral density. By age 6-12 months, however, the double mutant mice developed obesity, hyperleptinemia, fasting hyperglycemia, relative hypoinsulinemia, insulin resistance, and glucose intolerance; males were affected to a greater degree than females. The combination of perinatal growth failure and late-onset obesity and insulin resistance suggests that the lactogen resistant/GH¬deficient mouse may serve as a model for the development of the metabolic syndrome.
Dr. Freemark 's work has focused on the roles of the lactogenic hormones in perinatal and postnatal insulin production. He has made the novel observation that PRLRs in the human fetus and fetal rat are expressed only in pancreatic exocrine tissue and ductal epithelial cells in early gestation, emerging in pancreatic beta cells near the time of birth. Since the emergence of PRLRs in pancreatic beta cells coincides with a surge of beta cell proliferation and insulin production, he hypothesized that lactogens might play roles in islet maturation. Subsequent studies lent strong support to this hypothesis.
The lactogenic and somatogenic hormones have overlapping actions in a number of metabolic systems. Consequently, some effects of lactogen resistance might be obscured by compensatory actions of growth hormone. To address this problem, his laboratory has recently generated a mouse with combined deficiencies in lactogen signaling and GH production. This mouse is unique among experimental models of somatolactogen production and action. The model was created by breeding prolactin receptor (PRLR)-deficient (knockout) males with GH-deficient ("little") females. In contrast to mice with isolated GH- or PRLR-deficiencies, double mutant (lactogen-resistant and GH-deficient) mice on day 7 of life had growth failure and hypoglycemia These findings suggest that lactogens and GH act in concert to facilitate weight gain and glucose homeostasis during the perinatal period. Plasma insulin, IGF-I and IGF-H concentrations were decreased in both GH-deficient and double-mutant neonates but were normal in PRLR-deficient mice. Body weights of the double mutants were decreased markedly during the first 3-4 months of age, and adults had striking reductions in femur length, plasma IGF-I and IGF binding protein-3 concentrations, and femoral bone mineral density. By age 6-12 months, however, the double mutant mice developed obesity, hyperleptinemia, fasting hyperglycemia, relative hypoinsulinemia, insulin resistance, and glucose intolerance; males were affected to a greater degree than females. The combination of perinatal growth failure and late-onset obesity and insulin resistance suggests that the lactogen resistant/GHdeficient mouse may serve as a model for the development of the metabolic syndrome.
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Christopher Newgard, PhD, Professor of Pharmacology, Cancer Biology and Internal Medicine and Director of the Sarah Stedman Center for Nutritional Studies/Metabolics Center
Dr. Newgard's laboratory is interested in gaining a fundamental understanding of metabolic regulatory mechanisms, and in the application of this understanding to the development of new therapies for the epidemic diseases of diabetes and obesity. The work is organized around two ambitious practical goals that encompass smaller and more approachable basic science projects, summarized as follows:
• Development of a replenishable and protectable source of insulin secreting cells for cell-based therapy of Type 1 diabetes
• Development of new therapies for Type 2 diabetes and related diseases.
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Rebecca Buckley , M.D. , Professor of Pediatrics ( Al )
The overall emphasis of research in this laboratory is in human T- and B-cell development and in aberrations in their development and regulation. The work involves three particular areas of investigation: 1) the human primary immunodeficiency diseases; 2) human thymic education; and 3) regulation of human IgE synthesis. Methodology includes monoclonal antibody analyses of lymphocyte phenotypes, a variety of T-cell and NK cell functional assays, T-cell cloning, analysis of defects in T-cell signaling, and assessment of B-cell differentiation through measurement of immunoglobulin synthesized and secreted into supernatants of cultured blood mononuclear cells (MNC). This laboratory was the first to measure human IgE synthesis by cultured blood MNC. A highly reproducible system of studying IgE synthesis in vitro was discovered in this laboratory and involves use of a special tissue culture medium and recombinant human IL-4 or IL 13, with and without anti-CD4O and/or hydrocortisone. One of the largest (if not the largest) populations of patients with well-defined primary immunodeficiency diseases in this country is available for study. Phenotypic analyses of lymphocytes from the large number of infants with SCII) followed here recently led to the discovery by this laboratory of two previously unidentified molecular defects resulting in the human SCID syndrome, Jak 3 deficiency and IL7Ra chain deficiency. A major interest in this laboratory over the past seventeen years has been in the developing immune function of human infants with severe combined immunodeficiency disease (SCID) following transplants of HLAidentical or haploidentical (post-thymic T-cell depleted) bone marrow cells. Studies are ongoing examining T- and B-cell ontogeny, the extent of chimerism, the nature of immune cell cooperation between genetically disparate cells, mechanisms of tolerance induction and MHC restriction of genetically dnor Tcells that have been educated in these SCID thymi.
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Mary Louise Markert , M.D. , Ph.D., Associate Professor of Pediatrics Immunology
Dr. Markert 's laboratory focuses on immunoreconstitution in patients with inherited and acquired forms of immunodeficiency. At present she is working with patients with DiGeorge Syndrome and HIV infection. Infants with DiGeorge syndrome are born with no thymus and have no circulating T-cells. She is developing thymic transplantation for this disorder and are using these clinical experiments to learn about the role of the thymus in postnatal T-cell differentiation.
Clinical Interests:
Thymic transplantation for DiGeorge syndrome, inherited immunodeficiency states
Research Interests:
Dr. Markert is currently investigating thymus transplantation in complete DiGeorge syndrome. Complete DiGeorge syndrome is a fatal genetic disorder in which patients have heart defects, severe parathyroid hypoplasia and absence of the thymus. In a research protocol complete DiGeorge patients who have no T cells are transplanted with postnatal cultured human thymic epithelial tissue. The transplants are later biopsied to evaluate whether host stem cells have migrated to the tranplanted tissue and developed into T cells. Forty nine infants with complete DiGeorge anomaly have been transplanted and 35 survive (71%). Her research to date has shown that the patient can develop new host T cells in the graft and normal T cell proliferative responses to mitogens and antigens. Thus, in infants born with no T cells because of DiGeorge syndrome, cultured donor postnatal thymic tissue is sufficient for the development of host T cells from host stem cells. Dr. Markert has recently expanded her research to include parathyroid transplantation to treat the profound hypoparathyroidism seen in a subgroup of patients. Four have been transplanted and parathyroid hormone has developed in each.For additional information double click here ...
The environment for research in neonatal lung development and repair is also
excellent. Research opportunities include: alterations in gas transport and
sepsis-associated lung injury, pulmonary and cardiovascular physiology, gas
transport, and coagulation-mediated lung injury, nitric oxide and reactive
oxygen species biology and biochemistry, surfactant, cell biological and organ
explant methods of manipulating lung development with state-of-the-art morphometric
reconstruction of the developing lung. A particular strength of this program
is the opportunity for a fellow to use an acute lung injury model in the adult
baboon
Richard L. Auten, MD, Associate Professor of Pediatrics (Neonatology)
Dr. Auten's interests are in modulation of inflammatory response/oxidative injury during the newborn lung injury in rodent models of chronic lung disease of prematurity, targeting neutrophil and macrophage chemokinesis/function and cellular oxidative injury to preserve normal lung development. He is also interested in the effects of enhanced antioxidant enzyme expression in transgenic mice overexpressing extracellular superoxide dismutase during postnasal oxidant stress and in gene therapy using transient transfection of extracellular superoxide dismutase in newborn animal models.
Dr. Auten's laboratory focuses on the oxidative and inflammatory disruption of postnatal lung development. Transgenic and knockout mice lacking key inflammatory functions, as well as the use of chemokine and leukocyte function inhibitors are used to determine the dominant mechanisms responsible for disrupted alveolar and airway development. Perinatal exposure to oxidative stressors like ozone and other inhaled pollutants is being studied to determine the effects of multiple, combined exposures on disrupted airway development in collaboration with investigators in the Nicholas School of the Environment.
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Neil R. MacIntyre, MD, Professor of Medicine
Research Interests: 1) Mechanical Ventilation and respiratory failure. Current projects involve studying patient-ventilator interactions during modes of support that require patient activity. The focus is on ventilatory muscle function during these assisted modes. An additional new project will study the vasodilating properties of inhaled nitric oxide in patients receiving mechanical ventilation. Duke is also one of several institutions in the NIH ARDS Network, a consortium designed to perform multi-center trials. 2) Diffusing capacity of the lung for carbon monoxide. Current projects involve using a rapidly responding gas analyzer to measure lung diffusing capacity in discrete regions of the lung. 3) Exercise in obstructive lung disease. Current projects involve studying the physiology of cardio-respiratory conditioning in patients with obstructive lung disease. Study subjects are patients undergoing the Duke Pulmonary Rehabilitation Program. 4) Aerosol delivery systems. The current project is the development of a prototype aerosol generating catheter that can be directly inserted into the airways. 5) Lung volume reduction surgery. Duke is one of 18 institutions participating in a unique NIH-HCFA contract to perform a long term follow-up study of lung volume reduction surgery.
Dr. MacIntyre is interested in pulmonary gas exchange during acute and chronic lung disease and assessment of regional differences in pulmonary diffusing capacity. He is also interested in applications of high frequency jet ventilation to enhance gas exchange and/or decrease pulmonary barotrauma, determination of the effects of different types of mechanical ventilation on the work of breathing and weaning from mechanical ventilation.
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Thomas M. Murphy, M.D., Associate Professor of Pediatrics (Pulmonology)
Dr. Murphy 's laboratory is studying the following topics related to airway smooth muscle responsiveness: 1) Early Origins of Airway Hyperresponsiveness-- the Smooth Muscle Contribution; 2) Ontogenic Changes in Airway Smooth Muscle Relaxation; 3) Maturational Changes in ASM Plasticity; and 4) Role of a Putative NAD(P)H Oxidase in ASM Proliferation and Contractility.
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Claude A. Piantadosi, MD, Professor of Medicine
Dr. Piantadosi's laboratory has a special expertise in mechanisms of acute organ failure, especially lung injury (ALI), and an emphasis on the molecular biology that governs the importance of the physiological gases— oxygen, carbon monoxide and nitric oxide— in the pathogenesis and regulation of the responses to acute tissue injury. The basic science focuses on the control of oxidative metabolism by redox mechanisms, and the effects of reactive oxygen and nitrogen species in acute inflammatory lung injury. Because clinically ALI has such a high mortality, which is poorly understood scientifically, the objectives of work are to elucidate mechanisms of ALI related to the activation and deregulation of host defenses and crosstalk between inflammation and coagulation by redox events produced during exposure to hyperoxia, bacterial infection, and cytokines/chemokines elaborated as part of innate immunity. The approach relies on physiology, pathology, and cell and molecular biology to measure the integrated response to injury in order to decipher the injury mechanisms as well as to design and test specific interventions to prevent them. Another portion of the work is devoted to understanding the implications of ALI in terms of failure of non-pulmonary organs, which is a key to understanding the high mortality of this patient population. The organ systems of interest include the heart, brain, liver, and kidney, and especially the tissue damage caused by sepsis and septic shock. The laboratory focuses on animal models of disease, most heavily transgenic and knockout mice, in order to understand how inflammatory pathogenesis impacts onmitochondrial energy provision, mitochondrial damage and signaling through the intrinsic programmed cell death (apoptosis) pathways as well as in organ recovery through mitochondrial biogenesis and cell proliferation.
Dr. Piantadosi's research focuses on regulation of oxidative metabolism, oxidative stress, and nitric oxide biology in the lung and other organs. A portion of the work is devoted to understanding the roles of oxidative and nitrosative stress during acute lung injury. Acute lung injury is produced experimentally by exposure to oxygen, ischemia, endotoxin, or endogenous inflammatory mediators. The physiological, biochemical and molecular responses of the lung are measured during the evolution of oxidative stress in order to understand the injury mechanisms and thereby be able to prevent it with specific interventions. Another part of the work is devoted to understanding the responses of non-pulmonary organs to acute lung injury and to severe sepsis. This work focuses on the central role of the mitochondrion in energy provision, signaling of programmed cell death (apoptosis) and the role of mitochondrial biogenesis in cell survival. The laboratory has a special expertise recognized on a national level in mechanisms of acute lung injury and multiple organ failure, especially the roles of oxygen, reactive oxygen species, and nitric oxide in the physiological and pathogenic responses to such injuries.
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Jonathan S. Stamler, MD, Professor of Medicine and Biochemistry, Associate Investigator of the Howard Hughes Medical Institute:
Dr. Stamler is a member of the new Translational Medicine Initiative (TMI) at Duke. He is internationally recognized for his study of NO and its role in normal and pathophysiological conditions. The impact of his studies is emphasized by his multiple publications in Nature, Science, Cell, and The Proceedings of the National Academy of Sciences, USA. Dr. Stamler is a member of the American Association of Physicians and has received many awards for his research. In 2000, he was an ASCI prize finalist, and in 2001 the AFMR prize winner. Dr. Stamler’s research focuses on the regulation of redox systems as they relate to complex physiological responses, focusing specifically on nitric oxide (NO). By studying the molecular details of the interactions of NO with thiol and transition metal-containing proteins, insights are gained into the molecular basis of redox sensitivity in biological systems, and new molecules can be generated with therapeutic applications. The role of redox systems in organ damage, for example hyperoxia, hypoxia, and pulmonary hypertension, make studies of this system very relevant to the training of the pediatric investigator.
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Mary Sunday, M.D., Professor of Pathology
Dr. Sunday's laboratory is focused on understanding early lung embryogenesis and early origins of lung injury. With regard to lung development, her lab is investigating the role of novel transcription factors (TRs) in regulating cell migrating and cell fate determination. Lung formation begins as an outpouching of ventral foregut on murine gestational day 0.5 (E9.5), followed by branching morphogenesis and cell differentiation. The central hypotheses are that specific TFs direct mammalian lung embryogenesis and pulmonary effects are due to downstream molecular and/or cellular events. Dr. Sunday's laboratory is testing these hypotheses using genetically deficient mice. These models are used to determine whether abnormal lung development might be linked to abnormal mesenchymal cell migration and/or cell differentiation. Additionally, the overall hypothesis is that bombesin-like peptide (BLP) is an early mediator of lung injury in bronchopulmonary dysplasia (BPD). Human infants with BPD have increased numbers of pulmonary neuroendocrine cells (PNECs) containing BLP. Elevated BLP could mediate lung injury in BPD, including interstitial fibrosis and reactive airway disease. New data indicates that premature infants with elevated urine BLP levels at days 2-5 of age have a 10-fold increased risk of BPD even when normalized for all other variables including prematurity. Elevated urine BLP levels also occur shortly after birth in 2 baboon models of BPD in which BLP levels correlate with severity of subsequent chronic lung disease (CLD). Postnatal therapy with anti-BLP monoclonal antibody 2A11 protects against BPD in both models. The lab is beginning to address hypotheses using hyperoxic newborn mice, validating this as a model of CLD with similarities to human BPD. It is being determined whether intratracheal BLP triggers specific pro-inflammatory cascades that also characterize hyperoxic CLD. Using both murine and baboon models, evaluations are being made whether BLP blocking antibody (SA11 and a human anti-BLP antibody) can function as prophylactic agents for CLD using a minimum dosage schedule. Furthermore, determining which BLP receptors might be involved in mediating hyperoxic CLD using mice deficient in one or more of the 3 cloned BLP receptors (GRP-R, BRS-3, and/or NMB-R). These studies will help to clarify cellular and molecular mechanisms by which BLP could contribute to the pathophysiology of BPD and facilitate the development of novel prophylactic treatments for infants at risk.
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Judith Voynow , M.D. , Associate Professor of Pediatrics (Pulmonary)
Our laboratory has been studying the regulation of the major respiratory tract mucins and their functions in the lung. Recently, her work has focused on the regulation of mucins by neutrophile lastase (NE), a major inflammatory mediator in CF. She has found that NE increases expression of two major respiratory tract mucins, MUC5AC and MUC4, and this effect is mediated by oxidant stress. Furthermore, she found that NE regulates these mucins by a post-transcriptional regulatory mechanism. Current research endeavors include: 1) identification of the RNA-binding regulatory proteins for MUC expression, 2) analysis of the oxidants/pro-oxidant enzymes regulating MUC expression and 3) evaluation of the mechanisms of airway remodeling following NE exposure.
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Jo Rae Wright , Ph.D. , Professor of Cell Biology
Dr. Wright studies the functions of pulmonary epithelial and immune cells at the cellular and molecular level. These two types of cells carry out functions that are important for normal breathing and for preventing infection. The alveolar epithelial type II cell synthesizes a substance known as surfactant, which is a soap-like mixture of lipids and proteins that reduces surface tension in the lung and makes normal breathing possible. One aspect of her research is directed toward understanding the metabolism and clearance of surfactant and the role that receptors and surfactant proteins play in regulating surfactant pool size. The type II cell, in addition to synthesizing surfactant, participates in surfactant clearance by endocytosis. Her group is currently attempting to isolate the type H cell receptor, define the molecules and pathways involved in intracellular targeting of surfactant, and determine the factors that regulate endocytosis. Two of the surfactant proteins have been shown to be homologous to serum proteins that bind carbohydrates and are involved in non-antibody mediated host defense against infection. This observation has generated a new area of research on the immunomodulatory.
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v. Neural Injury
and Repair in the Fetus and Neonate:
Opportunities for fellow research in neural injury and repair are excellent.
The NPRI has a fully equipped laboratory within the Multidisciplinary Neuroprotection
Laboratory and has access to any of the techniques or models used. This program
encompasses a number of models of central nervous system injury including
stroke, head injury and hypoxic ischemia injury in neonatal rats and mice.
The fellow will have access to laboratory facilities to investigate basic
mechanism of acute brain injury and potential pharmacologic interventions
using whole animal and molecular biology techniques.
Daniel Laskowitz, MD, Associate Professor of Medicine (Neurology) and Neurobiology
Dr. Laskowitz’s laboratory uses molecular biology, cell culture, and animal modeling techniques to examine the CNS response to acute injury. In particular, his laboratory examines the role of microglial activation and the endogenous CNS inflammatory response in exacerbating the secondary injury following acute brain insult. Much of the in vitro work in his laboratory is dedicated to elucidating cellular responses to injury with the ultimate goal of exploring new therapeutic interventions in the clinical setting of stroke, intracranial hemorrhage, and closed head injury. In conjunction with the Multidisciplinary Neuroprotection Laboratories, he also focuses on clinically relevant small animal models of acute CNS injury. The laboratory uses murine models of closed head injury, subarachnoid hemorrhage, intracranial hemorrhage, and perinatal hypoxia-ichemia, in addition to the standard rodent models of focal stroke and transient forebrain ischemia. Recently he has adapted several of these models from the rat to the mouse to take advantage of the murine transgenic technology.
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James McNamara, MD, Carl R. Deane Professor of Neuroscience, and Chair,
Department of Neurobiology; Professor of Medicine (Neurology); Director, Center
for Translational Neuroscience
Dr. McNamara's research is centered on elucidating the molecular mechanisms of epileptogenesis, the process by which a normal brain becomes epileptic. Insight into the molecular mechanisms will provide novel targets for development of therapies aimed at prevention of epilepsy or limiting its progression.
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David Warner, MD, Professor of Anesthesiology, Neurobiology and Surgery, Mentor: Stroke, cerebral vasospasm, and head injury can be catastrophic diseases.
Dr. Warner’s multidisciplinary neuroprotective laboratory is dedicated to examining the pathophysiologic basis of and therapeutic modalities for treatment of these disorders. In vivo rodent models are established with requisite physiologic control. Experimental techniques include intracerebral microdialysis, neurochemistry, electrophysiology, measurement of cerebral blood flow and metabolic rate, neurohistology, image analysis, and neurobehavior. In vitro techniques include use of primary neuronal cultures and organotypic hippocampal slices in assays of excitotoxicity and calcium transients. Therapeutic protocols examine effects of anesthetic agents, induced hypothermia, excitatory neurotransmitter antagonists, free radical scavengers, and allosteric modulators of hemoglobin affinity for oxygen on outcome from brain injury. Transgenic and knockout murine models are used to examine the roles of human apolipoprotein E isoforms and human extracellular superoxide dismutase in global and focal cerebral ischemia and head injury.
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Track II – Clinical Scientist Track (Clinical Research):
The fellow is a part of the clinical research team in the Division and is
expected to develop his/her own questions that can serve as a testable hypothesis.
Clinical research opportunities in this area include: a) NICHD Neonatal Network
(Ronald Goldberg, M.D.); b) Randomized Trial of a Benchmarking Intervention
to Increase Survival with BPD; c) Induced Hypothermia (body cooling) for Encephalopathy;
and Aggressive Versus Conservative Phototherapy for the Extremely Low Birthweight
Infant. Additional clinical research opportunities exist as well in clinical
database access and neurodevelopmental outcomes.
Daniel K. Benjamin, Jr., MD, MPH, Ph.D., Associate Professor of Pediatrics
Dr. Benjamin’s interests include nosocomial neonatal bacteremia and candidemia. He is the National Principal Investigator for a multi-center trial of new tools to diagnose neonatal candidiasis, and two multi-center trials for drug trials for pediatric indication. He is also the Principal Investigator and Protocol Chair for several multi-center studies to investigate the pharmacokinetics of antimicrobial agents in premature infants
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Debra Brandon, RN, PhD
Dr. Brandon is Assistant Professor of Nursing. She joined the faculty of the Duke University School of Nursing in the fall of 1999 and has practiced as a neonatal clinical nurse specialist at Duke University Hospital since 1993. Her research interests involve the effects of the hospital environment on the health and development of preterm infants, in particular the effects of earlier than normal sensory stimulation on short and long-term inter-sensory development and health outcomes.
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Robert Califf, MD, Associate Vice Chancellor for Clinical Research, Director of the Duke Clinical and Translational Research Institute, Professor of Medicine (Cardiology)
Dr. Califf has particular research interests in the methods and infrastructure of clinical and translational research. Within his medical specialty of cardiology, he has focused on clinical trials in acute coronary syndromes, heart failure and secondary prevention. The DCRI offers a wide variety of clinical research tools and training as part of its mission of providing translational and clinical research. Dr. Califf coordinates and directs the ongoing clinical research and clinical trials as well as being involved with development of novel trial formats and analysis techniques. Two junior faculty members of the Division are being mentored by Dr. Califf (Dr's. Michael Cotten and Daniel Benjamin).
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C. Michael Cotten, M.D., Assistant Professor of Pediatrics Neonatology
Dr Cotten is the Director of Neonatal Clinical Research at Duke. He is the alternate site Principle Investigator for the NICHD Neonatal Research Network, and is the Director of the Special Care Nursery at Durham Regional Hospital . His research focuses on variation in individual infants' risks of complex diseases of prematurity. His work has involved assessment of center differences in risk of morbidities and mortality in high risk infants. With Network and Duke colleagues, he and Dr. Goldberg have received NICHD funds to develop a DNA repository for the Network's extremely low birthweight infants at the Duke Center for Human Genetics. This resource will allow large scale genetic association studies in high risk premature infants. He serves on the NICHD Neonatal Network's Genomics Subcommittee. He has completed a Master's Degree in Clinical Research at the DCRI and serves on the Duke IRB .
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Ronald N. Goldberg, MD, Professor of Pediatrics, Director of Neonatology
Dr. Goldberg’s interests include the cardiovascular manifestations of sepsis and septic shock in the neonate with specific attention to the role of cytokines and nitric oxide and the use of nitric oxide and ethyl nitrite in persistent pulmonary hypertension. In addition, he has been involved in clinical research and Multicenter Collaboration involving nitric oxide, surfactant and high frequency ventilation. He is the PI representing Duke in the NICHD Neonatal Network and has been a recipient, along with Dr. Jonathan Stamler, of the Duke Translational Medicine Research Award. He has a major interest in the perinatal asphyxia and has developed a Phase I study evaluating autologous cord blood transfusions in these patients.
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Ricki F. Goldstein, MD, Assistant Professor of Pediatrics (Neonatology), Associate
Dr. Goldstein’s research interest is in neurodevelopmental follow-up of high-risk infants with a particular emphasis on long-term outcome of extremely low birth-weight premature infants and full term infants treated with extracorporeal membrane oxygenation or high frequency ventilation for respiratory failure. She is studying clinical predictors of outcome as well as genetic factors that affect susceptibility to brain and neurologic recovery after injury has occurred.
Dr. Goldstein's developmental group has also been involved in creating an educational program for well-child care providers and community interventionists concerning the post-discharge care of premature and other high-risk infants. She is also the follow-up PI to the NICHD Neonatal Network.For additional information double click here ...
Diane Holditch-Davis, RN, PhD
Dr. Holditch-Davis received her doctorate in developmental psychobiology at the University of Connecticut in 1985. She will join the faculty of the Duke University School of Nursing in January 2006. From 1985-2005, she was on the faculty of UNC-Chapel Hill. Dr. Holditch-Davis' research focuses on identifying risk for preventing long-term developmental and health problems in high-risk infants. She is currently principal investigator on an R01 testing the effectiveness of a nursing support intervention for rural, African-American mothers of preterm infants. The goal of this intervention is to reduce developmental delays by improving the mother's psychological well-being, improving the mother-infant relationship, and getting mothers to use early intervention and health services for their infants. She has been PI on 2 other NINR-funded studies examining how biological risk as measured by behavioral sleep-wake state development, EEG dysmaturity, visual attention, and perinatal neurological insults interact with social risk (quality of mother-infant interactions and the social environment) to result in developmental and health outcomes of preterms. She has utilized her expertise with observational methods to measure parent-child interactions as a co-investigator on multiple studies, including 2 studies testing an intervention to treat depressive symptoms in low-income Latina, African-American, and white mothers, a study of parental role attainment in parents of medically fragile infants, and a study of parental care giving of infants seropositive for HIV.
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Jennifer Li, M.D., Pediatric Cardiology
Dr. Li is a graduate of Duke University School of Medicine and has been a member of the Duke faculty for 13 years. She is currently the Director of the Pediatric Clinical Research Initiative at the DCRI and has expertise in pediatric cardiology, cardiac imaging, and clinical trials. Under her direction, the DCRI has coordinated multiple NIH- and industry-sponsored pediatric projects in cardiology, infectious diseases, and neuro-psychiatry. She was the principal investigator for an industry-sponsored international, multi-center study to evaluate the safety and effectiveness of a range of fosinopril doses in the treatment of children with hypertension. She was the principal investigator for an industry-sponsored international multi-center study to evaluate the pharmacodynamics of clopidogrel in infants with cyanotic congenital heart disease and Blalock-Taussig shunts. Dr. Li is also a co-investigator for the North Carolina Consortium for the NIH-NHLBI Pediatric Heart Network. She has participated in several other multi-center clinical trials in pediatric cardiology including studies on TP10, amlodipine, and intra-cardiac devices. She has an appointment in the Office of the Commissioner at FDA to evaluate pediatric drug clinical trials. Because of her dedication and experience in pediatric clinical research and her leadership skills in the DCRI, Dr Li is well-situated to mentor clinical research training.
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William F. Malcolm, M.D., Associate Professor of Pediatrics
Dr. Malcolm is Associate Professor of Pediatrics. He joined the faculty in 2002. He provides clinical care in the Intermediate Transitional Care Nursery. Dr. Malcolm's clinical interests include caring for the convalescent infant and medical and neurodevelopmental follow-up. He is the medical liaison for the developmental team. His research includes a 3 year study of GERD in VLBW newborns, (Gerber Foundation) in collaboration with Boston Children's Hospital Department of Pediatrics, Gastroenterology, he is using a multi-channel intraluminal impedance technique to accurately assess acid and non-acid reflux. Dr. Malcolm is investigating intraluminal impedance technique to accurately assess acid and non-acid reflux. Dr. Malcolm is investigating methods to prevent enteral feeding failures in infants with surgical NEC and short gut syndrome.
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Ross E. McKinney, M.D., Host Defense, Mentor: Dr. Ross McKinney, Associate Professor of Pediatrics, is a member of the Division of Pediatric Infectious Diseases and Vice Dean for Research for the Duke University of School of Medicine.
Dr. McKinney is a long time member of the Pediatric AIDS Clinical Trials Group. He is also PI of the North Carolina Collaborative Center (Duke and UNC) in the NICHD funded Pediatric Pharmacology Research Unit Network. He is also a member of the Executive Committee of the PPRU Network.
Dr. McKinney began working with pediatric HIV infection in 1986 in a phase I clinical trial at Duke (in collaboration with the NCI and the University of Miami). The first child known to receive AZT (now Zidovudine) began his therapy at Duke. Our Pediatric Infectious Disease group was also the first to propose the trial to use maternal AZT treatment to prevent vertical transmission of HIV from mother to infant. Dr. McKinney and our Division subsequently championed this study.
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Courtney Thornburg , M.D. , M.S. Assistant Professor of Pediatrics
Dr. Thornburg is trained in pediatric hematology/oncology and completed a National Hemophilia Foundation Clinical Fellowship in Pediatric Hemostasis and Thrombosis. Her primary clinical and research interests relate to pediatric hemostasis and thrombosis. Dr. Thornburg sees children for the evaluation of bleeding symptoms including easy bruising, epistaxis, menorrhagia, excessive bleeding after tooth extraction or surgery, and abnormal coagulation tests. She takes care of children with bleeding disorders such as hemophilia, von Willebrand disease, and platelet function defect and children. She also takes care of children with thrombosis including deep venous thrombosis, pulmonary embolus and sinovenous thrombosis, and evaluates children who are asymptomatic but have a family history of thrombosis or risk factor for thrombosis. Dr. Thornburg is part of the Hemostasis and Thrombosis Center at Duke University Medical Center ( http://htc.medicine.duke.edu/ ). The Hemostasis & Thrombosis Center is participating in a multi-center project coordinated and funded by the Centers for Disease Control and Prevention (CDC) ( http://www.cdc.gov/ncbddd/hbd/default.htm ). The purpose of this project is to characterize the types of patients referred to the Center. Data collected from this study will help us learn more about medical care and management for patients with bleeding and clotting disorders.
Dr. Thornburg 's research interests include outcomes related to maternal/fetal thrombosis and hemostasis, screening for prothrombotic risk factors, genetic modifiers of von Willebrand disease, and treatment adherence in patients with hemophilia and sickle cell anemia. In addition, Dr. Thornburg participates in the NIH sponsored Transfusion Medicine Hemostasis Clinical Trials Network ( http://www.tmhnetwork.org/ ).
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Geoffrey Ginsburg MD Ph.D., Institute of Genomic Sciences and Policy
http://www.genome.duke.edu/people/faculty/ginsburg/Dr. Geoffrey Ginsburg , Director of the Duke Institute for Genome Sciences and Policy's Center for Genomic Medicine, was recently appointed to the board of the newly created Personalized Medicine Coalition (PMS). The Coalition is an independent, non-profit group that works to advance the understanding and adoption of personalized medicine. Defined as the use of molecular analyses to better manage a patient's disease or disease predisposition, personalized medicine has the potential to change the way we thing about, identify and manage health problems. The PMC was formed to provide leadership in the scientific, clinical and policy arenas within this rapidly emerging field.
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David Goldstein, M.D.
http://www.dukehealth.org/physicians/483A7121BC91782C85256DFD006A933AGeneral Research Focus: Cerebrovascular Disease. Research efforts have involved several aspects of cerebrovascular disease. In the laboratory, work has centered on developing an understanding of the mechanisms underlying pharmacological modulation of motor recovery after injury to the cerebral cortex and has led to several clinical studies in patients with stroke and traumatic brain injury. Research in stroke has also focused on health policy issues related to the use of carotid endarterectomy and optimization of stroke prevention strategies. Research involving new therapies for acute stroke has been carried out through clinical trials. Specific Approaches: Laboratory Research: Studies of recovery after sensorimotor cortex injury have focused on measurement of neurobehavioral recovery as influenced by systemically administered drugs modulating the activities of specific central neurotransmitters. This work has involved behavioral measures, stereotactic lesioning, basic neurochemistry, cerebral microdialysis, and immunocytochemistry. Health Policy Research: Work has focused on clinical health policy related to cerebrovascular disease carried out in conjunction with the Center for Clinical Health Policy Research. These studies have centered on the utilization of carotid endarterectomy and the optimization of secondary and tertiary stroke prevention with an emphasis on outcome measures. Clinical Trials: Principal investigator at Duke for several stroke acute treatment trials including studies of GM1-ganglioside and several neuroprotective drugs including CGS-19755 (Selfotel), Eliprodil, and a glycine receptor anatagonist. Principal or co-investigator at Duke for several stroke prevention trials including the NIH-supported study of carotid angioplasty and stenting as compared with carotid endarterectomy (CREST), RESPECT (PFO closure), PROfESS (antiplatelet drugs and angiotensin receptor blocker). In addition, principal investigator for NIH-supported studies related to poststroke recovery and steering committee for SPARCL (statin for secondary stroke prevention).
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Huntington Willard , Ph.D. , Director of the Duke University Institute for Genome Sciences and Policy
Dr. Willard is a leader in emerging fields of genomics. He was recently recruited from his position as director and president of the research institute of University Hospitals of Cleveland . Research in Dr. Willard 's laboratory focuses on aspects of the molecular structure and function of human chromosomes and the human genome. The overall goal is to understand chromosomal mechanisms involved in gene control and/or implicated in genetic disorders. Mammalian X chromosome inactivation results in the cis-controlled inactivation of most, but not all, genes along the length of one of the two X chromosomes in females during embryogenesis. Studies include cloning and characterization of human genes that appear to "escape" inactivation, identification and cloning of the X inactivation center in mouse and humans that controls the cis effect and appears to be required for inactivation to occur, and mapping, cloning, and analysis of genes involved in X-linked disease. Centromeres of mammalian chromosomes are structurally complex. The dominant class of DNA at human centromeres is a family of highly repeated, tandemly arrayed satellite DNA. Current efforts are directed at determining the cytological and molecular organization of long arrays of alpha satellite, which measure 300-5,000 kb in length, at examining aspects of centromere function in a series of abnormal X chromosomes found in patients, and at establishing functional tests of centromere function in cell culture systems, as a step towards assembly of artificial human chromosomes.
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Vamsee Pamula, Ph.D.
Digital microfluidics is an alternative paradigm for lab-on-a-chip systems based upon micromanipulation of discrete droplets. Microfluidic processing is performed on unit-sized packets of fluid which are transported, stored, mixed, reacted, or analyzed in a discrete manner using a standard set of basic instructions. In analogy to digital microelectronics, these basic instructions can be combined and reused within heirarchical design structures so that complex procedures (e.g. chemical synthesis or biological assays) can be built up step-by-step. And in contrast to continuous-flow microfluidics, digital microfluidics works much the same way as traditional bench-top protocols, only with much smaller volumes and much higher automation. Thus a wide range of established chemistries and protocols can be seamlessly transferred to a nanoliter droplet format.
For additional information see: www.liquidlogic.com
Kenneth Dodge, PhD, William McDougall Professor of Public Policy, Professor of Psychology Director, Center for Child and Family Policy
Ken Dodge is interested in the application of behavioral science research to issues in public policy that affect children and families. He joined the faculty of the Sanford Institute in September of 1998. He is trained as a clinical and developmental psychologist, having earned his B.A. in psychology at Northwestern University in 1975 and his Ph.D. in psychology at Duke University in 1978. Prior to joining the faculty at Duke, Dodge served on the faculty at Indiana University, the University of Colorado, and Vanderbilt University. Dodge is the first director of the Center for Child and Family Policy Center. In this role, he leads an effort to bridge basic scientific research in children's development with public policy affecting children and families. The Center provides an integrated system of research, debate and dissemination, public service, and teaching, addressing issues of child and family policy.
Professor Dodge studies the development and prevention of violent behavior by youth and within families. He has articulated a comprehensive model of how chronic violence develops in youth and has tested the model with longitudinal inquiry and laboratory experiments. This model has led to the creation of a preventive intervention program called Fast Track, which randomized trials have proven effective in preventing serious conduct disorder. Professor Dodge also created the Durham Family Initiative, which is a field experiment to lower the child abuse rate for an urban community.
Dr. Dodge's website: http://www.childandfamilypolicy.duke.edu/People/faculty_staff/dodge.html
David T. Tanaka, MD, Professor of Pediatrics (Neonatology), Associate Chief of Neonatology
Dr. Tanaka’s interest and energies have focused on a thorough and sophisticated analysis of health care finances and resource allocation. He has created a multidisciplinary team, which has been given sufficient authority by the Chancellor of the Medical School and Duke Health Care System and the Chief Financial Officer of the Duke Health Care System to identify and correct system errors involved with either acquisitions or expenditure of clinical revenues. His work has resulted in improvement in system efficiency and revenue enhancement. He has created a partnership within an academic setting that has improved the financial health of the Medical School and Medical Center, and resulted in support of the Division’s and Medical School’s academic mission. The ultimate aim of Dr. Tanaka's work is to elucidate systems problems and systematic errors in financial reimbursement that lend themselves to statistical analysis and correction. All academic institutions need to be able to approach their finances in a scientific, systematic manner if they are to survive. Dr. Tanaka is developing tools in concert with SAS, which may be applicable to and testable at all centers. In addition, Dr. Tanaka is working with members of the Sanford Institute of Public Policy at Duke to evaluate health care policy and resource utilization.
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Asif Ahmad, M.D.
Asif Ahmad is vice president for Diagnostic Services and chief information officer for Duke University Health System and Duke University Medical Center . He provides leadership, direction, and strategic planning for the information technology staff and functions in support of the Health System. As the Vice President Diagnostic Services he is responsible for developing the overall strategy of diagnostic support for DUHS . Additionally, Mr. Ahmad is responsible for overseeing the Health Information Management group for the health system.
Mr. Ahmad earned a double bachelor’s degree in electrical engineering and telecommunications at the University of Engineering and Technology of Lahore, Pakistan, and earned an M.S. in Biomedical Engineering and an M.B.A. at the Fisher College of Business at Ohio State University. He came to Duke by way of The Ohio State University Health System where he received the highest national award for excellence in computerization of the patient record - The Nicholas E. Davies Award. He and DUHS were profiled by InformationWeek magazine in their September 2005 issue as 500 top innovators in the IT Industry (1 of 42 in Healthcare). He also received the 2001, 2002 and 2005 Most Wired Health System Award, which awards the top 100 hospitals nationally, and the 2002 Innovator Award, American Hospitals Association for excellence in wireless and online patient care workflow. He is a board member of the National Alliance Health Information Technology.
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Jeffrey Ferranti, M.D., M.S., Clinical Associate in Pediatrics (Neonatology)
Director of Pediatric Informatics, Duke University Health System
Director of Computerized Patient Safety Initiatives, DUHS
Clinical Interests: Medical informatics, computerized patient safety initiatives, quality improvement metrics, electronic research data exchange, medical data standards and interoperability, neonatal critical care, CPOE, electronic medical records Research Interests: Pediatric Informatics - Computerized Physician Order Entry (CPOE)in Pediatrics - Electronic Medical Records (EMR) in Pediatrics - Emerging Technologies in Neonatology - Healthcare Data Standards and Taxonomies
Dr. Ferranti provides physician leadership to support the ongoing development and implementation of pediatric information systems throughout the health system. He is the clinical leader of the pediatric CPOE project, and is responsible for developing and implementing computerized safety metrics to evaluate the impact of technology on the care of children. He is also responsible for the strategic planning of IT initiatives related to Adverse Drug Event surveillance and computerized patient safety initiatives. He is the principle investigator of an AHRQ grant entitiled "Automated Adverse Drug Event Detection and Intervention".
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William Hammond, Ph.D. , Professor of Community and Family Medicine and Biomedical Engineering
Dr. Hammond oversees research in the Division of Medical Informatics that focuses on the creation and dissemination of health care data and with related knowledge. Areas of investigation include networking, database structures, query languages, report generation, decision support, standards for healthcare data interchange, and workstations. Research takes place in the context of creating computer-based patient records and using those records for patient care, research education, administration, and finance. Students working in this laboratory observe and participate in a full range of activities from hardware and software to testing systems in biomedical application areas. A typical project involves the analysis of alternative approaches, creation of a new informatics tool, and use and evaluation of the effectiveness of that tool in solving an application problem in a real world setting. The Medical Informatics division is home of the Duke half of the DukeUNC Training Program in Medical Informatics, one of ten such grant programs supported by the National Library of Medicine. This interdisciplinary program draws on 25 years of research experience in medical informatics and nearly as many years of experience with operational computer-based patient record systems at Duke. Resources include various Digital Equipment Corporation VAX computers and a Microsoft NT network connected to the Medical Center fiber backbone. In addition, these computers are connected to an IBM 3090 mainframe running a hospital information system. Areas of development include an intensive care setting, regional obstetrical databases, and primary care setting.
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