Core Faculty of the Harvard Neonatal-Perinatal Medicine Fellowship Program
Pankaj Agrawl, MD MMSc
Dr. Agrawal's research focuses on the genetic basis and molecular mechanisms of rare diseases with special focus on congenital skeletal muscle disorders. His goals are:
- As Medical Director of the Gene Discovery Core, Manton Center for Orphan Disease Research, Boston Children's Hospital, enrolling patients with orphan diseases and finding the genetic cause for the disease. Several candidate genes are currently being pursued by him for rare diseases such as ROHHAD syndrome, Ohtahara syndrome, non-specific congenital myopathies.
- Understanding the molecular role of cofilin-2, an actin-binding protein, in various organs including muscle, lungs and heart. He has created a conditional KO and human mutation carrying knockin cofilin-2 mouse models. He is also employing zebrafish models to understand this protein's functions.
Long-term, his research will help patients with orphan diseases without an identifiable cause. Identifying molecular basis for their disease will help find new potential therapies in the future.
- Agrawal PB, Strickland CD, Midgett C, Poulos M, Morales A, Newberger D, Ryan MM, Iannaccone ST, Beggs AH. Heterogeneity of nemaline myopathy cases with skeletal muscle aactin gene mutations. Annals of Neurology. 2004;56:86-96.
- Agrawal PB, Greenleaf RS, Tomczak KK, Lehtokari V-L, Wallgren-Pettersson C, Wallefeld W, Laing NG, Darras BT, Maciver SK, Dormitzer PR, Beggs AH. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. American Journal of Human Genetics. 2007;80:162-7.
- Pierson CR, Agrawal PB, Blasko J, Beggs AH. Myofiber size correlates with MTM1 mutation type and outcome in X-linked myotubular myopathy. Neuromuscul Disorders. 2007;17:562-8.
Mandy Brown Belfort, MD MPH
Dr. Belfort’s research focuses on the long-term outcomes of infant growth and nutrition. Her interests include:
- The effect of rapid infant weight gain on beneficial cognitive outcomes as well as adverse obesity-related outcomes.
- How the balance of risks and benefits of rapid weight gain differs in preterm vs. full term infants.
- Identifying valid and cost-effective measures of neurodevelopment that can be used to follow large populations of former preterm infants over time.
- The effect of intravenous omega-3 fatty acids on neurodevelopment.
Ultimately Dr. Belfort hopes that her research will lead to better nutritional practices for all infants, as well as better overall health later in life
- Belfort MB, Rifas-Shiman SL, Rich-Edwards J, Kleinman K, Gillman MW. Size at Birth, Infant Growth, and Blood Pressure at 3 Years of Age. J. Pediatr. 2007 Dec;151(6):670-4.
- Belfort MB, Rifas-Shiman SL, Rich-Edwards J, Kleinman K, Oken E, Gillman MW. Maternal Iron Intake and Iron Status During Pregnancy and Child Blood Pressure at 3 Years of Age. Int J Epidemiol. 2008 Apr;37(2):301-8.
- Belfort MB, Rifas-Shiman SL, Rich-Edwards J, Kleinman K, Oken E, Gillman MW. Infant Growth and Child Cognition at 3 Years of Age. Pediatrics. 2008 Sep;122(3):e689-95.
Dara Brodsky, MD
Dr. Brodsky's area of interest is medical education. She recently developed an interactive computer-based module for neonatology fellows focused on the “Principles of Teaching and Learning”. She has also co-written a Neonatology board review book (Brodsky, Martin) and co-edited a book for primary care clinicians caring for premature infants (Brodsky, Ouellette). Her current research areas include:
- Evaluating changes that occurred in clinical practice after BIDMC NICU team training workshops
- Describing the characteristics of difficult conversations in the NICU by qualitatively examining narratives from a multi-disciplinary group of clinicians
- Establishing rating standards for peer observation of medical lectures followed by training others to use this rating standard
- Brodsky D, Martin C. Neonatology Review. 2nd edition. lulu. 2010.
- Brodsky D, Ouellette MA. Primary Care of the Premature Infant. Elsevier. 2007.
- Newman L, Brodsky D, Vollmer C, Roberts D, Johansson A, Atkins KM, Schwartzstein R. “Determining Precise Expert Rating Standards for the Peer Observation of Medical Lectures.” Pending.
Heather Herson Burris, MD MPH
Dr. Burris studies potential underlying mechanisms behind racial disparities in preterm birth and poor fetal growth. Her goals are to:
- Understand whether micronutrient differences account for disparities in preterm birth including multivitamins and vitamin D.
- Explore whether epigenetic mechanisms such as DNA methylation contribute to disparities in preterm birth
Ultimately, Dr. Burris’s research may identify targets for interventions to reduce the incidence of preterm birth and its associated racial/ethnic disparities.
- Burris HH, Collins JW. Race and preterm birth; the case for epigenetic inquiry. Ethnicity and Disease. 2010;20:296-299.
- Burris HH, Mitchell AA, Werler MM. Pericionceptional Multivitamin Use and Infant Birth Weight Disparities. Annals of Epidemiology. 2010;20(3):233-240.
- Burris HH, Werler MM. U.S. Provider Reported Folic Acid or Multivitamin Ordering for Non-Pregnant Women of Childbearing Age; NAMCS and NHAMCS, 2005-2006. Maternal Child Health Journal. 2010. (Epub ahead of print March 5, 2010).
- Burris HH, Collins JW, Wright RO. Racial/ethnic disparities in preterm birth; clues from environmental exposures. Current Opinion in Pediatrics. 2011. (Epub ahead of print February 4, 2011).
Sule Cataltepe, MD
Dr. Cataltepe’s research focuses on regulation of angiogenesis in normal and pathological lung development as well as retinopathy of prematurity. Her studies also investigate the role of proteinase/antiproteinase balance in chronic lung disease of prematurity. Her research goals are to:
- Identify mechanisms that regulate angiogenesis during normal and pathological lung development.
- Investigate mechanisms of pathological neovascularization in retinopathy of prematurity.
- Examine the role of proteinase/antiproteinase imbalance in development of chronic lung disease of prematurity.
Ultimately, these studies may unravel novel mechanisms that could contribute to the development of improved therapies for common diseases of premature infants, such as chronic lung disease and retinopathy of prematurity.
- Hirakawa H, Pierce RA, Bingol-Karakoc G, Karaaslan C, Weng M, Shi, GP, Saad, A, Weber E, Mariani, TJ, Starcher B, Shapiro SD, Cataltepe S. Cathepsin S deficiency confers protection from neonatal hyperoxia-induced lung injury. Am J Respir Crit Care Med. 2007 Oct 15;176(8):778-85.
- Elmasri H, Karaaslan C, Teper Y, Ghelfi E, Weng M, Ince TA, Kozakewich H, Bischoff J, Cataltepe S. Fatty Acid Binding Protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. Faseb J. 2009 Nov; 23(11):3865-73.
- Ghelfi E, Karaaslan C, Berkelhamer S, Akar S, Kozakewich H, Cataltepe S. Fatty Acid Binding Proteins and Peribronchial Angiogenesis in Bronchopulmonary Dysplasia. Am J Respir Cell Mol Biol. 2011 Sep;45(3):550-6.
Helen Christou, MD
Dr. Christou's research focuses on the effects of acidosis on vascular homeostasis. The current focus is the role of acidosis in the development of pulmonary hypertension. Her goals are to:
- Define the molecular mechanisms underlying regulation of gene expression by extracellular acidosis in vascular cells.
- Examine the functional significance of acidosis-induced changes in gene expression in vascular cells.
- Determine the in vivo effects of extracellular acidosis in animal models of pulmonary hypertension.
The Christou lab uses rodent models of pulmonary hypertension and a combination of in vivo physiologic and imaging studies to understand the effects of acidosis in this disease. In a complementary approach, they pursue molecular and cellular studies in isolated blood vessels and vascular cells to define the molecular mechanisms of the observed physiologic effects.
- Brenninkmeijer L, Kuehl C, Geldart AM, Arons E, Christou H. Heme oxygenase-1 does not mediate the effects of extracellular acidosis on vascular smooth muscle cell proliferation, migration, and susceptibility to apoptosis. J Vasc Res. 2011;48(4):285-96. Epub 2011 Jan 26.
- Mam V, Tanbe AF, Vitali SH, Arons E, Christou HA, Khalil RA. Impaired vasoconstriction and nitric oxide-mediated relaxation in pulmonary arteries of hypoxia- and monocrotaline-induced pulmonary hypertensive rats. J Pharmacol Exp Ther. 2010 Feb;332(2):455-62. Epub 2009 Nov 13.
- Guan J, Wu X, Arons E, Christou H. The p38 mitogen-activated protein kinase pathway is involved in the regulation of heme oxygenase-1 by acidic extracellular pH in aortic smooth muscle cells. J Cell Biochem. 2008 Dec 1;105(5):1298-306.
Dmitry Dukhovny, MD MPH
Dr. Dukhovny’s academic focus involves applying cost-effectiveness analysis and decision science to help optimize resource utilization and allocation in neonatal intensive care, a critical issue given the current constraints on the health care system
Ultimately, Dr. Dukhovny’s research hopes to assist the decision makers towards optimal and cost-effective resource utilization in the NICU, especially as new health care technologies are introduced to the field.
- Dukhovny D, Lorch SA, Schmidt B, Doyle LW, Kok JH, Roberts RS, et al. Economic Evaluation of Caffeine for Apnea of Prematurity. Pediatrics. 2011;127(1):e146-e55.
- Kamholz K, Dukhovny D, Kirpalani H, Whyte RK, Roberts RS, Wang N, Mao W, Zupancic JAF and the Premature Infants in Need of Transfusion Study Group. Economic Evaluation Alongside the Premature Infants in Need of Transfusion (PINT) Randomized Controlled Trial. Archives of Childhood Diseases. 2011. (Published online 7/6/2011 doi:10.1136/adc.2010.206102).
- Dukhovny D, Zupancic JAF. Economic Evaluation With Clinical Trials in Neonatology. NeoReviews. 2011;12(2):e69-e75.
P. Ellen Grant, MD
Dr. Grant is the Director of the Fetal-Neonatal Neuroimaging and Developmental Science Center (FNNDSC) at Children's Hospital Boston. The center's purpose is to create the infrastructure and provide the expertise needed to support and foster cutting edge clinical and translational science research involving magnetic resonance imaging (MRI), magnetoencephalography (MEG) and near-infrared spectroscopy (NIRS) across multiple subspecialties.
Dr. Grant holds a Master of Science degree in physics and an MD from the University of Toronto. She did her radiology residency at Vancouver General Hospital in British Columbia, Canada, and her fellowship in adult and pediatric neuroradiology at the University of California, San Francisco. She is now an associate professor of radiology at the Harvard Medical School.
Dr. Grant headed the Division of Pediatric Radiology at Massachusetts General Hospital for five years before moving to Children's Hospital Boston to become the founding director of the Fetal-Neonatal Neuroimaging and Developmental Science Center and the first incumbent of Children's Hospital Boston Chair in Neonatology. At Children's she holds appointments in the Division of Newborn Medicine and the Department of Radiology.
Dr. Grant is a co-author of two popular textbooks for clinical neuroradiology and has won a number of awards for her research efforts as well as recognition for her clinical excellence.
- Hagmann P, Sporns O, Madan N, Cammoun L, Pienaar R, Wedeen VJ, Meuli R, Thiran J-P, Grant PE. White Matter Maturation Reshapes Structural Connectivity in the Late Developing Human Brain. (Accepted to PNAS.)
- Takahashi E, Dai G, Rosen GD, Wang R, Ohki K, Folkerth RD, Galaburda AM, Wedeen VJ, Grant PE. Developing Neocortex Organization and Connectivity in Cats Revealed by Direct Correlation of Diffusion Tractography and Histology. Cereb Cortex. 2010 May 21. PMID: 20494968.
- Vishwas MS, Chitnis T, Pienaar R, Healy BC, Grant PE. Tract-based analysis of callosal, projection, and association pathways in pediatric patients with multiple sclerosis: a preliminary study. AJNR Am J Neuroradiol. 2010 Jan; 31(1):121-8. Epub 2009 Oct 22.
- Madan N, Grant PE. New Directions in Clinical Imaging of Cortical Dysplasias. Epilepsia 2009 Oct; 50 Suppl 9:9-18. PMID: 19761449.
James Gray, MD
Dr. Gray's previous research includes development of methods for performing cross-institutional assessments of NICU outcomes. Currently, his research is focused on advancing the integration of evolving information technologies into the practice and evaluation of newborn care. He is currently working to evaluate the impact of medical device technologies in Neonatal Intensive Care.
- Gray JE, Safran CA, Davis RB, Pompilio-Weitzner G, Stewart JE, Zaccagnini L, Pursley DM. Baby CareLink: Using the Internet and Telemedicine to Improve Care for High Risk Infants. Pediatrics. 2000;106:1318-1324.
- Gray JE, Goldmann DA. Medication errors in the NICU: Special Patients, Unique Issues. Arch Dis Child. 2004 Nov;89(11):472-473.
- Gray JE, Ursprung R, Edwards WH, Horbar JD, Nickerson J, Plsek P, Shiono PH, Suresh G, and Goldman DA. Patient MisIdentification in the NICU: Quantification of Risk. Pediatrics. 2006 Jan;117:e43-47.
Munish Gupta, MD MMSc
Dr. Gupta is interested in quality improvement, patient safety, and clinical innovation in neonatal intensive care. His work includes projects covering numerous areas of clinical care, with a particular focus on the respiratory support of preterm infants and determinants of bronchopulmonary dysplasia. His interests include:
- Understanding how variations in clinical care can affect the risk of bronchopulmonary dysplasia.
- Developing innovative new approaches to measuring and improving quality of clinical care.
- Fostering collaborative approaches to quality improvement among NICUs utilizing comparative data and benchmarking.
Ultimately, Dr. Gupta hopes to contribute to novel methods of quality assurance and quality improvement in neonatal care in general, and in particular, to improving the respiratory care of preterm infants.
- Gupta M, Mestan KK, Martin CR, Pearson C, Ortiz K, Fu L, Stubblefield P, Cerda S, Kasnica JM, Wang X. Impact of clinical and histologic correlates of maternal and fetal inflammatory responses on gestational age in preterm births. J Matern Fetal Neonatal Med. 2007:20:39-46.
- Gupta M, Pursley DM. A survey of infection control practices for influenza in mother and newborn units in U.S. hospitals. Am J Obstet Gynecol. 2011 Jun:204(6 Suppl 1):S77-83.
- Young BC, Dodge LE, Gupta M, Rhee JS, Hacker MR. Evaluation of a rapid, real-time intrapartum group B Streptococcus assay. Am J Obstet Gynecol. 2011 Oct:205:372.e1-6.
Stella Kourembanas, MD
Dr. Kourembanas' area of research is in newborn lung vascular biology. Using bench to bedside approaches, her group is investigating the vascular responses to hypoxia at the molecular, cellular, and in vivo level. The long term goals of her research program are to:
- Understand better the pathobiology of pulmonary hypertension (PHtn) and the molecular mechanisms of developmental lung injury and repair leading to bronchopulmonary dysplasia (BPD). Studies in animal physiology and basic molecular biology are validated with studies in infants with lung disease using patient-derived material.
- Ongoing work in the laboratory also explores the role of mesenchymal stem cells (MSC) in the prevention and treatment of lung disorders that affect neonates and children. Dr. Kourembanas has demonstrated both prevention and reversal of lung vascular disease, and is actively pursuing molecular and cellular mechanisms of action.
Ultimately, Dr. Kourembanas' research may identify specific molecular targets for therapies of lung diseases, both to prevent and to reverse established injury.
- Wu X, Chang MS, Mitsialis SA., Kourembanas S. Hypoxia regulates bone morphogenetic protein signaling in vascular smooth muscle cells through CtBP-1. Circ. Res. 2006;99:240-247.
- Aslam M, Baveja R, Liang OD, Fernandez-Gonzalez A, Lee C, Mitsialis SA, Kourembanas S. Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am J Respir Crit Care Med. 2009 Dec 1;180(11):1122-30.
- Liang OD, Mitsialis SA, Chang MS, Vergadi E, Lee C, Aslam M, Fernandez-Gonzalez A, Liu X, Baveja R, Kourembanas S. Mesenchymal stromal cells expressing heme oxygenase-1 reverse pulmonary hypertension. Stem Cells. 2011 Jan;29(1):99-107.
- Vergadi E, Chang MS, Lee C, Linag OD, Liu X, Fernandez-Gonzalez A, Mitsialis SA, Kourembanas S. Early Macrophage Recruitment and Alternative Activation Are Critical for the Later Development of Hypoxia-induced Pulmonary Hypertension. Circulation. 2011 May 10;123(18):1986-95.
Paul Lerou, MD
Dr. Lerou's research goals are to advance the fundamental understanding of pluripotent stem cell biology and to explore how failure of genomic integrity impacts human development. They are developing novel live-cell and fixed-cell imaging techniques to study mitotic progression and genomic stability in human pluripotent stem cells. These techniques will be coupled with single cell analysis and computational biology approaches to improve our understanding of how cell cycle regulation and pluripotency are coupled. His research interests are:
- Human pluripotent stem cells: embryonic stem (ES) cells and induced pluripotency stem (iPS) cells
- Genomic stability regulation in human pluripotent stem cells
- Cell cycle regulation of human pluripotent stem cells
- p53 dynamics of human pluripotent stem cells
The most common and clinically problematic form of genomic instability is aneuploidy, a hallmark of cancer and a cause of infertility and congenital developmental defects. The causes of aneuploidy remain largely unknown, yet the impact on development is profound. Aneuploidy affects 35% of clinically recognized spontaneous abortions, 4% of stillborns and 3 in 1000 live borns. Neonatologists witness firsthand the consequences of aneuploidy on development when they care for couples that have struggled with infertility and whose infants are afflicted by genetic syndromes. The long term goal of Dr. Lerou's research will be to use human pluripotent stem cell research to improve our understanding of early human development and how genomic instability disrupts normal development and contributes to birth defects.
- Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2008 Jan 10;451(7175):141-6.
- Lerou PH, Yabuuchi A, Huo H, Miller JD, Boyer LF, Schlaeger TM, Daley GQ. Derivation and maintenance of human embryonic stem cells from poor-quality in vitro fertilization embryos. Nat Protoc. 2008;3(5):923-33.
- Park IH, Lerou PH, Zhao R, Huo H, Daley GQ. Generation of human-induced pluripotent stem cells. Nat Protoc. 2008;3(7):1180-6.
- Lerou PH, Yabuuchi A, Huo H, Takeuchi A, Shea J, Cimini T, Ince TA, Ginsburg E, Racowsky C, Daley GQ. Human embryonic stem cell derivation from poor-quality embryos. Nat Biotechnol. 2008 Feb;26(2):212-4.
Marie C. McCormick, MD ScD
Dr. McCormick's work focuses on the outcomes of high-risk neonates and interventions to improve their outcomes.
Her most recent project involved the follow-up at age 18 of a cohort of youth who had participated in a multi-site, randomized trial of early educational intervention for premature, low birth weight infants. These data are available for secondary analysis for students with fluency in SAS and statistics, and an interest in longitudinal development. To facilitate the follow-up of high-risk neonates, the members of the follow-up team are conducting a comparison of parental report on a structured questionnaire with the results of developmental testing in the clinic by trained professional observers. In addition, she is initiating a study on the predictors of depression in the mothers of NICU patients.
The outcome of this research is to define further the factors influencing the outcome of premature infants, especially those that may point to interventions to improve their outcomes.
- McCormick MC, Brooks-Gunn J, Buka SL, Goldman J, Yu J, et al. Early intervention in low birth weight premature infants: Results at 18 years for the Infant Health and Development Program. Pediatrics. 2006;117:771-780.
- McCormick MC, Behrman RE. The quiet epidemic of premature birth: commentary on a recent Institute of Medicine report. Ambul Pediatr. 2007;7:8-9.
Richard Parad, MD MPH
Dr. Parad has several areas of interest in molecular genetics (genotype-phenotype relationships and screening) and clinical research, particularly with regard to respiratory diseases in newborns (including chronic lung disease and cystic fibrosis). His goals are to:
- Understand the pathophysiologic mechanisms that lead to predisposition and development of chronic lung disease in premature newborns.
- Develop optimal clinical strategies for prevention and treatment of chronic lung disease.
- Improve the definitions of newborn lung diseases that lead to chronic respiratory morbidity.
- Evaluate the therapeutic potential for the antioxidant, SOD, for the prevention of chronic lung disease, retinopathy of prematurity, and neurologic injury.
- Optimize strategies for newborn screening for cystic fibrosis.
- Identify biomarkers for newborns at high risk of developing necrotizing enterocolitis.
Dr. Parad's research aims to protect premature newborn lungs from injury and optimize their pulmonary outcomes.
- Davis JM, Parad RB, Michele T, Allred E, Price A, Rosenfeld W. Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn superoxide dismutase. Pediatrics. 2003;111(3):469-76.
- Parad RB, Comeau AM. Diagnostic dilemmas resulting from the immunoreactive trypsinogen/DNA cystic fibrosis newborn screening algorithm. J Pediatr. 2005;147(3 Suppl):S78-82.
- Nathe KE, Parad R, Van Marter LJ, Lund CA, Suter EE, Hernandez-Diaz S, Boush EB, Ikonomu E, Gallington L, Morey JA, Zeman AM, McNamara M, Levy O. Endotoxin-directed innate immunity in tracheal aspirates of mechanically ventilated human neonates. Pediatr Res. 2009;66(2):191-6.
Xianhua Piao, MD PhD
Dr. Piao's research focuses on the molecular mechanisms that control normal brain development and malformation. Polymicrogyria is a brain malformation characterized by numerous (poly) small (micro) cortical foldings, named gyri. Recently, a new syndrome was described in which polymicrogyria is mainly localized to the frontal part of the cerebral cortex, but the rest of the cortex is relatively spared. Dr. Piao named this syndrome bilateral frontoparietal polymicrogyria (BFPP). Individuals with BFPP present severe mental retardation, gait difficulty, language impairment, and seizure disorders. Dr. Piao recently demonstrated that the causative gene of BFPP is GPR56, an orphan G protein-coupled receptor (GPCR). Little is currently known about how GPR56 regulates brain development, and what its binding partners are. Her short-term goal is to establish how GPR56 delivers signals to cells and regulates the normal development of the brain. Specifically, she is focusing her research activities in the following two areas:
- To study how GPR56 delivers signals to cells.GPR56 is a membrane protein that mediates the communication between cells and/or cell and extracellular matrix. Identifying the binding partners of GPR56 is the first step towards elucidating the GPR56 signaling. Using traditional protein pull-down assays, array analysis, and functional assays, she is hoping to dissect GPR56 signaling pathway.
- To characterize GPR56 function in a mouse model. BFPP is a radiological diagnosis. Its pathology is unclear and extremely difficult to study due to the unavailability of brain specimens from affected individuals. A mechanistic analysis of GPR56 function in a mouse model is an essential approach to furthering our understanding of normal brain development and the improper generation of BFPP. Brain phenotype will be observed in mice in which GPR56 expression is abolished.
Further functional analysis of GPR56 in a mouse model will provide new insights and potential novel mechanisms in brain development and the pathophysiology of cortical malformation. Achieving the proposed objectives will likely yield information essential for genetic counseling, screening, as well as prediction, prevention, and possible treatments for polymicrogyria syndromes.
- Piao X, Hill RS, Bodell A, Chang B, Basel-Vanagaite L, Straussberg R, Dobyns WB, Qasrawi B, Winter R, Innes AM, Voit T, Ross E, Michaud J, Descarie J, Barkovich AJ, Walsh CA. G-Protein-Coupled Receptor-Dependent Development of Human Frontal Cortex. Science. 2004;303:2033-2036.
- Li S, Jin Z, Koirala S, Bu L, Xu L, Hynes RO, Walsh CA, Corfas G, Piao X. GPR56 Regulates Pial Basement Membrane Integrity and Cortical Lamination. The Journal of Neuroscience. 2008;28(22):5817-26.
- Koiral S, Jin Z, Piao X, Corfas G. GPR56-regulated granule cell adhesion in essential for rostral cerebellar development. The Journal of Neuroscience. 2009;29(23):7439-49.
- Luo R, Jeong SJ, Jin Z, Strokes N, Li S, Piao X. G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination. Proc Natl Acad Sci USA. 2011 Aug 2;108(31):12925-30. Epub 2011 Jul 18.
Karen M. Puopolo, MD PhD
Dr. Puopolo’s research focuses on the epidemiology of neonatal early- and late-onset sepsis.
- The goal of her current basic research is to determine the microbiological factors mediating methicillin-resistant and methicillin-sensitive Staphylococcus aureus colonization and infection in the neonatal intensive care unit.
- The goals of her clinical research are to model risk factors for early- and late-onset infection in newborns, and to devise clinical strategies for prevention of these infections.
- Puopolo KM and Eichenwald EC. No Change in Ampicillin-Resistant, Neonatal Early Onset Sepsis over 18 Years. Pediatrics. 2010;125(5):e1031-8.
- Newman T, Puopolo KM, Wi S, Draper D, Escobar GJ. Interpreting Complete Blood Counts Soon After Birth in Infants at Risk for Sepsis. Pediatrics. 2010;126(5):903-909.
- Chiu CH, Michelow IC, Cronin J, Ringer SA, Ferris TG, Puopolo KM. Effectiveness of a Guideline to Reduce Vancomycin Use in the Neonatal Intensive Care Unit. Pediatr Infect Dis J. 2011:30(4):273-278.
- Puopolo KM, Draper D, Wi S, Newman TB, Zupancic J, Lieberman E, Smith M, Escobar GJ. Estimating the Probability of Neonatal Early-Onset Infection Based on Maternal Risk Factors. Pediatrics. 2011 Oct 24; published online doi: 10.1542/peds.2008-1536.
Lawrence Rhein, MD
Dr. Rhein is involved in clinical research related to long-term pulmonary outcomes of neonatal lung diseases, especially bronchopulmonary dysplasia. He is also involved in studies that utilize long-term recorded oximetry to identify patterns of oxygen desaturation and determine which patterns of desaturation affect long-term neurodevelopmental and respiratory outcomes.His goals are to:
- Define risk factors for pulmonary hypertension in patients with chronic lung disease of prematurity, and determine the significance of pulmonary hypertension in long-term pulmonary morbidities in premature infants
- Identify patterns of oxygen saturation during the NICU course that predict subsequent respiratory and neurodevelopmental morbidities in premature infants
- Identify optimal methods to safely wean infants from supplemental oxygen
Ultimately, Dr. Rhein hopes that his research will define which patterns of oxygen desaturation require intervention to optimize long-term outcomes.
- Kulik TJ, Rhein LM, Mullen MP. Pulmonary arterial hypertension in infants with chronic lung disease: will we ever understand it? J Pediatr. 2010 Aug;157(2):186-90.
- DeGrazia, M., Wilkinson, A., & Rhein, L. Assessment of current practices for weaning infants from car beds. Journal of Perinatology-Neonatology: Neonatal Intensive Care. 2010;23(2),12-15
- Bozzetti V, Tagliabue P, and Rhein L. Evaluation of Healthy Full-Term and Late Preterm Infants with Presenting With Apnea in the Newborn Nursery: A Comparison of Neonatal Apnea and Infantile Acute Life Threatening Event (ALTE). Journal of Neonatal-Perinatal Medicine. 2010;3(4):271-276.
- Palm K, Simoneau T, Sawicki G, and Rhein L. Assessment of Current Strategies for Weaning Premature Infants From Supplemental Oxygen in the Outpatient Setting. Advances in Neonatal Care. 2011 Oct;11(5):349-356.
Yang Shi, PhD
Dr. Shi’s research focuses on mechanisms of epigenetic regulation. His goals are to:
- Understand how histone methylation dynamics is regulated by both methyltransferases and demethylases.
- Examine how these modifications are recognized by specific effector proteins that lead to transcriptional activation or repression.
- Study how these changes translated into biological and pathological outputs.
Ultimately, Dr. Shi’s studies are aimed at understanding fundamental regulatory mechanisms that impact the epigenetic states of the cell. Given the growing evidence of epigenetics in human diseases, Dr. Shi's findings may instruct development of future therapeutics.
- Shi YJ, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004;119:941-953.
- Shi Y* and Whetstine J. Dynamic regulation of histone lysine methylation by demethylases. Mol. Cell. 2007;25:1-14. *Corresponding author.
- Qi HH*, Sarkissian M*, Hu GQ, Wang Z, Bhattacharjee A, Gordon DB, Gonzales M, Lan F, Ongushaha PP, Huarte M, Yaghi NK, Lim S, Garcia B, Brizuela L, Zhao KJ, Roberts TM+, Shi Y+. Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development. Nature. 2010;466:503-7.
Vincent C. Smith, MD MPH
Dr. Smith's conducts Health Services research on former preterm infants and their families. His goal is to:
- Understand why some preterm infants and their families do well after discharge from the NICU and others do not.
Ultimately, the goal of Dr. Smith's research is to create interventions to improve outcomes for all preterm infants and their families.
- Smith VC, Zupancic JA, McCormick MC, Croen LA, Greene J, Escobar GJ, Richardson DK. Rehospitalization in the first year of life among infants with bronchopulmonary dysplasia. J Pediatr. 2004;144(6):799-803.
Smith VC, Zupancic JA, McCormick MC, Croen LA, Greene J, Escobar GJ, Richardson DK. Trends in severe bronchopulmonary dysplasia rates between 1994 and 2002. J Pediatr. 2005;146(4):469-73.
?cited by Ariagno R.L. In: Year Book of Neonatal and Perinatal Medicine. Fanaroff A, Maisels MJ, Stevenson D, editors. Elsevier Mosby; 2006.
Smith VC, Young S, Pursley DM, McCormick MC, Zupancic JA. Are families prepared for discharge from the NICU? J Perinatol. 2009;29(4):623-629.
?cited by Papile L. In: Year Book of Neonatal and Perinatal Medicine. Fanaroff A, Benitz, WE, Donn SM, Neu J, and Papile L, editors. Elsevier Mosby; 2010.
Martha Sola-Visner, MD
Dr. Sola-Visner's research focuses on mechanisms underlying quantitative platelet disorders in neonates. Her goals are to:
- Establish the differences between neonatal and adult megakaryocytopoiesis at the molecular level, using microarray analysis.
- Examine the ability of neonates to up-regulate platelet production in response to increased platelet consumption, as compared to adults.
- Determine the in vivo effects of thrombopoietic growth factor administration on neonatal megakaryocytopoiesis.
Ultimately, Dr. Sola-Visner's research hopes to lead to better therapies for neonatal thrombocytopenia.
- Pastos KM, Slayton WB, Rimsza LM, Sola-Visner MC. Differential effects of recombinant thrombopoietin and bone marrow stromal conditioned media on neonatal vs. adult megakaryocytes. Blood. 2006;108:3360-3362.
- Sola-Visner MC, Christensen RD, Hutson A, Rimsza LM. Megakaryocyte size and concentration in the marrow of thrombocytopenic and non-thrombocytopenic neonates. Pediatric Research. 2007;61:479-484.
- Brown R, Rimsza LM, Pastos KM, Lawrence RM, Young L, Saxonhouse MA, Sola-Visner MC. Effects of sepsis on neonatal thrombopoiesis. Pediatric Research. 2008;64(4):399-404.
Linda Van Mater, MD MPH
Dr. Van Marter's focus is on the epidemiology of neonatal cardiopulmonary disorders, in particular, Bronchopulmonary Dysplasia (BPD) and Persistent Pulmonary Hypertension of the Newborn (PPHN). She studies the antecedents of BPD, one of the commonest and most significant sequelae of prematurity, in an effort to understand how immaturity and care practices interact to modulate a preterm infant's risk of developing BPD. Her research also aims to eucidate the epidemiologic exposures of a pregnant woman and/or the newborn infant that cause or modify risk of Persistent Pulmonary Hypertension among full-term infants. This life-threatening disorder cannot be diagnosed prenatally and usually affects otherwise normal term infants. The goals of Dr. Van Marter's research are to:
- Advance scientific understanding of the interaction of epidemiologic exposures of these two important neonatal cardiopulmonary disorders.
- Identify preventable exposures that will prevent or ameliorate the risk of BPD and/or PPHN.
- Van Marter L, Leviton A, Allred E, Pagano M, Sanocka U, Parad R, and Moore M, for the Developmental Epidemiology Network. Do markers of barotrauma and oxygen toxicity explain inter-hospital variation in rates of chronic lung disease? Pediatrics. 2000;105:1194-1201.
- Van Marter L, Leviton A, Allred E, Pagano M, Sullivan K, Cohen A, Epstein M. Persistent pulmonary hypertension of the newborn and smoking and aspirin and nonsteroidal antiinflammatory drug consumption during pregnancy. Pediatrics .1996;97:658-63.
- Van Marter LJ, Dammann O, Allred EN, Leviton A, Pagano M, Moore M, Martin C for the Developmental Epidemiology Network. Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants. J Pediatr. 2002;140:171-6.
- Van Marter LJ, Kuban KCK, et al. Does Bronchopulmonary Dysplasia Contribute to the Occurrence of Cerebral Palsy Among Infants Born Before 28 weeks of Gestation? Arch Dis Child FN. 2011;96:F20-F29.
John A. F. Zupancic, MD ScD
Dr. Zupancic's research focuses on improving the efficiency with which scarce health care resources are used in improving the health of children, and in particular, newborns. His two approaches to this area of health policy are to:
- Perform and improve the validity of economic evaluations alongside neonatal clinical trials. A systematic review of the neonatal literature showed that fewer than 1% of randomized controlled trials have associated economic evaluations, and that the methodological quality of those performed is poor (Pediatric Research. 2001; 49(4): 364A.). Economic evaluations currently underway by Dr. Zupancic and colleagues alongside multi-center clinical trials include (i) high versus low red blood cell transfusion thresholds for newborns; (ii) drug therapy for prevention of neonatal chronic lung disease; (iii) high versus low oxygen saturation thresholds for the prevention of retinopathy of prematurity; (iv) intermittent nasal ventilation for the reduction of chronic lung disease in premature infants; and (v) peer support for post-prevention of post-partum depression.
- Perform computer modeling to determine best practice when evidence is currently lacking or where empirical studies are infeasible. Most recently, this has focused on the use of discrete event simulation to assess the impact of diffusion and regionalization on the cost and efficacy of new device technologies.
- Zupancic JAF, Horbar JD, Richardson DK, Carpenter JH, Lee SK, Escobar GJ and the Vermont Oxford Network SNAP Pilot Project Participants. Revalidation of the Score for Neonatal Acute Physiology in the Vermont Oxford Network. Pediatrics. In press.
- Zupancic JAF, Richardson DK, O'Brien BJ, Cronin CG, Schmidt B, Roberts R, Weinstein MC and the Trial of Indomethacin Prophylaxis in Preterms Investigators. Retrospective economic evaluation of a controlled trial of indomethacin prophylaxis for patent ductus arteriosus in premature infants. Early Human Development. 2006;82(2):97-103.
- Zupancic JA, Richardson DK, O'Brien BJ, Eichenwald EC, Weinstein MC. Cost-effectiveness analysis of predischarge monitoring for apnea of prematurity. Pediatrics. 2003;111(1):146-152.