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The Center for Prevention of Preterm Birth brings together faculty from Cincinnati Children's and the University of Cincinnati College of Medicine to perform innovative, transdisciplinary research to reduce the rate of prematurity and infant mortality.
Louis J. Muglia, MD, PhD Co-Director, Perinatal Institute
Co-Director, Perinatal Institute
Director, Center for Prevention of Preterm Birth
Professor, UC Department of Pediatrics
Visit the Muglia Lab
Dr. Muglia has pioneered the in vivo analyses of regulation of the endocrine stress response and the molecular pathways leading to birth using novel genetically altered mutant mice. These studies have elucidated the importance of corticotropin-releasing hormone, glucocorticoids, and prostaglandins in neuroendocrine modulation, behavior, and perinatal adaptation. These studies have evolved over the last decade to specifically focus on the mechanisms controlling the timing for birth in humans using genetics and comparative genomics. The composition of the biological clock metering the duration of human gestation remains a central question in reproductive biology. The goal of the Muglia laboratory is to understand the molecular timing machinery comprising this biological clock to prevent or better treat human preterm labor and delivery.
Among Dr. Muglia’s achievements are more than 180 publications and many awards, including a Burroughs Wellcome Fund Career Development Award in the Biomedical Sciences, the Society of Pediatric Research Young Investigator Award, and election to the American Society for Clinical Investigation and Association of American Physicians. In 2010, Dr. Muglia was elected to fellow in the American Association for the Advancement of Science. He is an active member of the Society for Pediatric Research, Society for Neuroscience, and the Lawson Wilkins Pediatric Endocrine Society. Dr. Muglia currently serves as chair of the Board of Scientific Counselors for the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. In 2013, Dr. Muglia was elected to membership in the Institute of Medicine of the National Academies.
BS: University of Michigan, Ann Arbor, MI, 1981.
PhD: University of Chicago, Chicago, IL, 1986.
MD: University of Chicago, Chicago, IL, 1988.
Muglia LJ, Jacobson L, Dikkes P, Majzoub JA. Corticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need. Nature. 1995; 373:427-432.
Gross G, Imamura T, Luedke C, Vogt SK, Olson LM, Nelson DM, Sadovsky Y, Muglia LJ. Opposing actions of prostaglandins and oxytocin determine the onset of murine labor. Proc. Natl. Acad. Sci. USA. 1998; 95: 11871-11875.
Bethin KE, Nagai Y, Sladek R, Asada M, Sadovsky Y, Hudson TJ, Muglia LJ. Microarray analysis of uterine gene expression in mouse and human pregnancy. Mol Endocrinol. 2003; 17: 1454-1469.
Kistka Z A-F, Palomar P, Lee KA, Boslaugh SE, Wangler MF, Cole FS, DeBaun MR, Muglia LJ. Racial disparity in the frequency of recurrence of preterm birth. Am J Obstet Gynecol. 2007; 196: 131.e1-131.e6.
Roizen J, Asada M, Tong M, Tai H-H, Muglia LJ. Preterm birth without progesterone withdrawal in 15-hydroxyprostaglandin dehydrogenase hypomorphic mice. Mol Endocrinol. 2008; 22: 105-112.
Kolber BJ, Roberts MS, Howell MP, Wozniak DF, Sands MS, Muglia LJ. Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning. Proc Natl Acad Sci USA. 2008; 105: 12004 - 12009.
Plunkett J, Feitosa MF, Trusgnich M, Wangler MF, Palomar L, Kistka ZA-F, DeFranco EA, Shen TT, Stormo EAD, Puttonen H, Hallman M, Haataja R, Luukkonen A, Fellman V, Peltonen L, Palotie A, Daw EW, An P, Teramo K, Borecki I, Muglia LJ. Mother’s genome or maternally-inherited genes acting in the fetus influence gestational age in familial preterm birth. Human Heredity. 2009; 68: 209-219.
Kolber BJ, Boyle MP, Wieczorek L, Kelley CL, Kelley CL, Onwuzurike CC, Nettles SA, Vogt SK, Muglia LJ. Transient early-life forebrain corticotropin-releasing hormone elevation causes long-lasting anxiogenic and despair-like changes in mice. J Neurosci. 2010; 30: 2571-2581.
Muglia LJ, Katz M. The enigma of spontaneous preterm birth. N Engl J Med. 2010; 362: 529-535.
Plunkett J, Doniger S, Orabona G, Morgan T, Haataja R, Hallman M, Puttonen H, Menon R, Kuczynski E, Norwitz E, Victoria Snegovskikh V, Palotie A, Peltonen L, Fellman V, DeFranco EA, Chaudhari BP, McGregor TL, McElroy JJ, Oetjens MT, Teramo K, Boreck I, Fay J, Muglia L. An evolutionary genomic approach to identify genes involved in human birth timing. PLoS Genetics. 2011; 7: e1001365.
Amygdala Glucocorticoid Receptor Function in Stress. Principle Investigator. NIH/NIMH. Feb 2009-Dec 2014.
Maternal Temperament, Stress, Inflammation and Preterm Birth. Multi-PI. NIH/NICHD. Sep 2013-Aug 2017.
March of Dimes Prematurity Research Center Ohio Collaborative. Coordinating PI. March of Dimes. Jul 2013-Jun 2018.
Sandip Bhattacharyya, MSc, PhD Member, Center for the Prevention of Preterm Birth
is an immunologist, who has basic science research programs in inflammation biology and signal transduction. The major research interest of Dr. Bhattacharyya’s laboratory is to understand the molecular mechanisms of glucocorticoid action in innate immunity and define context-specific immunomodulatory functions.
Member, Center for the Prevention of Preterm Birth
Assistant Professor, UC Department of Pediatrics
Inflammation Immunology; signal transduction
Dr. Bhattacharyya received his doctoral degree in immunology and cell biology from Jadavpur University, India. His doctoral research shed light on multi-level regulation of host immune responses in experimental visceral leishmaniasis. During his post-doctoral training at the University of North Carolina, Chapel Hill, Dr. Bhattacharyya explored critical roles of Interleukin-10 for regulation of nuclear factor kappa B signaling pathway in dendritic cells. Later, at Washington University, St Louis and Vanderbilt University, Nashville, Dr. Bhattacharyya uncovered new mechanisms for glucocorticoid actions on Toll-like receptor-induced inflammatory pathways. His findings provided evidence for signal-dependent glucocorticoid sensitivity. Dr. Bhattacharyya’s study indicated that the spectrum of TLRs activated determines their responsiveness to steroid therapy.
Dr. Bhattacharyya was selected for the Ramanujan Fellowship, 2011, awarded by the Department of Science and Technology, Government of India.
BSc: Chemistry, University of Calcutta, Calcutta, India.
MSc: Biochemistry, University of Calcutta, Calcutta, India.
PhD: Cell Biology and Immunology, Jadavpur University, Calcutta, India.
Post Doctoral Fellowship: University of North Carolina, Chapel Hill, NC.
Senior Scientist: Washington University, Saint Louis, MO / Vanderbilt University, Nashville, TN.
Ratajczak C.K., Asada M, Allen, G.C., McMahon, D.G., Muglia, L.M., Smith, D., Bhattacharyya, S., and Muglia, L.J. Generation of myometrium-specific Bmal1 knockout mice for parturition analysis. Reproduction, Fertility and Development. 2012;24(5):759-67.
Bhattacharyya S, Kay T, Zhao Z, Muglia LJ. Glucocorticoids Target suppressor of cytokine synthesis 1 (SOCS1) and Type 1 Interferons to Regulate Toll-like Receptor-induced STAT1 Activation. Proc Natl Acad Sci USA. 2011;108(23):9554-9559.
Bhattacharyya, S, Ratajczak CK, Vogt SE, Kelley C, Colonna M, Schreiber RD. Muglia, LJ. TAK1 Targeting by Glucocorticoids Determines JNK and IkB Regulation in Toll-like Receptor-Stimulated Macrophages. Blood. 2010;115(10):1921-1931.
Kim HJ, Zhao H, Kitaura H, Bhattacharyya S, Brewer JA, Muglia LJ, Ross FP, Teitelbaum SL. Glucocorticoids and the osteoclast. Ann N Y Acad Sci. 2007;1116:335-339.
Bhattacharyya S, Brown DE, Brewer JA, Vogt SE, Muglia LJ. Glucocorticoid receptor regulates toll-like receptor-4 mediated inflammatory responses by inhibition of p38 MAP kinase. Blood. 2007;109(10):4313-4319.
Kim HJ, Zhao H, Kitaura H, Bhattacharyya S, Brewer JA, Muglia LJ, Ross FP, Teitelbaum SL. Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest. 2006;116(8):2152-2160.
Bhattacharyya S, Sen P, Wallet M, Long B, Baldwin AS Jr., Tisch R. Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of IkappaB kinase activity. Blood. 2004;104(4):1100-1109.
Sen P, Bhattacharyya S, Wallet M, Wong CP, Poligone B, Sen M, Baldwin AS, Jr., Tisch, R. NF-kappa B hyperactivation has differential effects on the APC function of nonobese diabetic mouse macrophages. J Immunol. 2003;170(4):1770-1780.
Bhattacharyya S, Ghosh S, Dasgupta B, Mazumder D, Roy S, Majumdar S. Chemokine-induced leishmanicidal activity in murine macrophages via the generation of nitric oxide. J Infect Dis. 2002;185(12):1704-1708.
Bhattacharyya S, Ghosh S, Jhonson PL, Bhattacharya SK, and Majumdar S. Immunomodulatory role of interleukin-10 in visceral leishmaniasis: defective activation of protein kinase C-mediated signal transduction events. Infect Immun. 2001;69(3):1499-1507.
James M. Greenberg, MD Co-Director, Perinatal Institute
investigates the developmental biology of pulmonary vascular development, including how vascular endothelial growth factor (VEGF) mediates pulmonary vascular, lymphatic and airway development. He studies how VEGF mediates organization of pulmonary vasculature during late fetal life as well as how certain proteins implicated in axonal guidance during central nervous system development also direct developmental processes in the lung.
Director, Division of Neonatology
Neonatal chronic lung disease; late preterm infant
MD: University of Illinois College of Medicine, Chicago, IL, 1977-1981.
Pediatric Internship and Residency: University of Minnesota Hospital and Clinic, Minneapolis, MN, 1981-1984. Chief Resident, Department of Pediatrics, University of Minnesota Hospital and Clinic, Minneapolis, MN, 1984.
Fellowship: Immunology/Neonatology, University of Minnesota Hospital and Clinic, Minneapolis, MN, 1985-1987; 1988-1989; visiting scientist, Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, England.
Certification: American Board of Pediatrics, 1988; subspecialty board, Neonatal/Perinatal Medicine, 1989.
Binder S, Hill K, Meinzen-Derr J, Greenberg JM, Narendran V. Increasing VLBW Deliveries at Subspecialty Perinatal Centers via Perinatal Outreach. Pediatrics. 2011 Mar;127(3):487-93.
Kulkarni RM, Herman A, Ikegami M, Greenberg JM, Akeson AL. Lymphatic ontogeny and effect of hypoplasia in developing lung. Mech Dev. 2011 Jan-Feb;128(1-2):29-40.
Kulkarni RM, Greenberg JM, Akeson AL. NFATc1 regulates lymphatic endothelial development. Mech Dev. 2009 May-Jun;126(5-6):350-65.
Mallory BP, Mead TJ, Wiginton DA, Kulkarni RM, Greenberg JM, Akeson AL. Lymphangiogenesis in the developing lung promoted by VEGF-A. Microvasc Res. 2006 Jul-Sep;72(1-2):62-73.
Preciado DA, Rutter MJ, Greenberg JM, Bahado-Singh R, Lambers D, Willging JP. Intrapartum management of severe fetal airway obstruction. J Otolaryngol. 2004 Oct;33(5):283-8.
Akeson AL, Cameron JE, Le Cras TD, Whitsett JA, Greenberg JM. Vascular endothelial growth factor-A induces prenatal neovascularization and alters bronchial development in mice. Pediatr Res. 2005 Jan;57(1):82-8.
Greenberg JM, Thompson FY, Brooks SK, Shannon JM, Akeson AL. Slit and robo expression in the developing mouse lung. Dev Dyn. 2004 Jun;230(2):350-60.
Le Cras TD, Spitzmiller RE, Albertine KH, Greenberg JM, Whitsett JA, Akeson AL. VEGF causes pulmonary hemorrhage, hemosiderosis, and air space enlargement in neonatal mice. Am J Physiol Lung Cell Mol Physiol. 2004 Jul;287(1):L134-42.
Akeson AL, Greenberg JM, Cameron JE, Thompson FY, Brooks SK, Wiginton D, Whitsett JA. Temporal and spatial regulation of VEGF-A controls vascular patterning in the embryonic lung. Dev Biol. 2003 Dec 15;264(2):443-55.
Greenberg JM, Thompson FY, Brooks SK, Shannon JM, McCormick-Shannon K, Cameron JE, Mallory BP, Akeson AL. Mesenchymal expression of vascular endothelial growth factors D and A defines vascular patterning in developing lung. Dev Dyn. 2002 Jun;224(2):144-53.
Mihaela Pavlicev, PhD
PhD: University of Vienna, Austria, 2003.
Postdoc: Washington University St. Louis (with Jim Cheverud), University of Oslo (with Thomas Hansen).
Pavličev M, Wagner GP. A model of developmental evolution: selection, pleiotropy, compensation. TrEE. 2012;27: 316-322.
Pavličev M, Hansen TF. Genotype-phenotype maps maximizing evolvability: modularity revisited. Evolutionary Biology. 2011;38: 371-389.
Pavličev M, Norgard EA, Fawcett GL, Cheverud JM. Evolution of pleiotropy: Epistatic interaction pattern supports a mechanistic model underlying variation in genotype-phenotype map. J. Experimental Zoology B. 2011;316B: 371-385.
Pavličev M, Wagner GP, Cheverud JM. Evolution of adaptive phenotypic variation patterns by direct selection on evolvability. Proc. Roy. Soc. 2011;278: 1903-1912.
Pavličev M, Le Rouzic AP, Wagner GP, Cheverud JM, Hansen TF. Directionality of epistasis in a murine intercross population. Genetics. 2010;185:1489-1505.
Pavličev M, Cheverud JM, Wagner GP. Measuring morphological integration using eigenvalue variance. Evolutionary Biology. 2009;36:157-170.
Wagner GP, Kenney-Hunt JP, Pavličev M, Peck JR, Waxman D, and Cheverud JM. Pleiotropic scaling of gene effects and the "Cost of complexity". Nature. 2008;452: 470-472.
Pavličev M, Kenney-Hunt JP, Norgard AE, Roseman CC, Wolf J, and Cheverud JM. Genetic variation in pleiotropy: Differential epistasis as a source of variation in the allometric relationships between bone lengths and body weight. Evolution. 2008;62 (1): 199-213.
Wagner GP, Pavličev M, Cheverud JM. The road to modularity. Nature Reviews Genetics. 2007;8: 921- 931.
Sing Sing Way, MD, PhD Pauline and Lawson Reed Chair, Division of Infectious Diseases
is an infectious disease physician-scientist. He cares for infants and children with infection related illness, and provides consultation in the diagnosis and prevention diseases caused by communicable agents. Dr. Way supervises an active basic research laboratory that uses basic immunological approaches to investigate ways to boost host defense and protection against infection. If you have interest in this work, please contact Dr. Way.
Pauline and Lawson Reed Chair, Division of Infectious Diseases
Associate Professor, UC Department of Pediatrics
Infectious diseases; prenatal infection; immunology
Dr. Way is an infectious disease physician-scientist. He cares for infants and children with infection related illness, and provides consultation in the diagnosis and prevention diseases caused by communicable agents. Dr. Way supervises an active basic research laboratory that uses basic immunological approaches to investigate ways to boost host defense and protection against infection. Ongoing projects investigate the immune basis responsible for enhanced susceptibility to infection during pregnancy, the immune pathogenesis of pregnancy complications that occur with maternal infection, and the basic signals required for stimulating immune cell activation.
Dr. Way trained in the combined MD/PhD program at the Albert Einstein College of Medicine, pediatric residency at the University of California San Francisco, and infectious disease fellowship at the University of Washington. During fellowship training, Dr. Way began investigating the basic immunology and immune pathogenesis of infectious diseases relevant to human, and in particular, infant and child health.
Dr. Way’s research has been supported by the National Institutes of Health since 2006. Dr. Way’s research has been described in many publications in numerous prestigious scientific journals including Nature, Cell Host & Microbe, PLoS Pathogens, and The Journal of Immunology. The past and ongoing work has also been recognized by numerous prestigious awards including the Infectious Diseases Society of America Wyeth Young Investigator Award, a Basil O’ Conner Award from the March of Dimes Foundation, and the Investigator in Pathogenesis of Infectious Diseases award from the Burroughs Wellcome Fund.
MD PhD: Albert Einstein College of Medicine, Bronx, NY, 1999.
Residency: University of California San Francisco, San Francisco, CA, 2001.
Fellowship: University of Washington, Seattle, WA, 2004.
Rowe JH, Ertelt JM, Xin L, Way SS. Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature. 490: 102-106. 2012.
Rowe JH, Ertelt JM, Xin L, Way SS. Listeria monocytogenes cytoplasmic entry induces fetal wastage by disrupting maternal Foxp3+ regulatory T cell-sustained fetal tolerance. PLoS Pathog. 8: e1002873. 2012.
Rowe JH, Ertelt JM, Way SS. Innate IFN-g is essential for Programmed death ligand-1-mediated T cell stimulation following Listeria monocytogenes infection. J Immunol. 189: 876-84. 2012.
Rowe JH, Ertelt JM, Way SS. Foxp3+ regulatory T cells, immune stimulation, and host defense against infection. Immunology. 136:1-10. 2011.
Ertelt JM, Johanns TM, Mysz MA, Nanton MR, Rowe JH, Aguilera MN, Way SS. Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection. Immunology. 134: 487-97. 2011.
Ertelt JM, Rowe JH, Mysz MA, Singh C, Roychowdhury M, Aguilera MN, Way SS. Foxp3+ regulatory T cells impede the priming of protective CD8+ T cells. J Immunol. 187: 2569-77. 2011.
Rowe JH, Ertelt JM, Aguilera MN, Farrar MA, Way SS. Foxp3+ regulatory T cell expansion required for sustaining pregnancy compromises host defense against prenatal bacterial pathogens. Cell Host Microbe. 10:54-64. 2011.
Johanns TM, Law CY, Kalekar LA, O’Donnell H, Ertelt JM, Rowe JH, Way SS. Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to recurrent infection. Microbes Infect. 13: 322-330. 2011.
Han JY, Hanson DC, Way SS. Herpes Zoster and meningitis due to reactivation of varicella vaccine virus in a immunocompetent child. Pediatr Infect Dis J. 30:266-268. 2011.
Ertelt JM, Johanns TM, Rowe JH, Way SS. IL-21-independent pathogen-specific CD8+ T cell expansion, and IL-21-dependnent suppression of CD4+ T cell IL-17 production. Immunology. 131: 183-191. 2010.
Maternal regulatory T cells control the immune pathogenesis of prenatal infection. Principal Investigator in the Pathogenesis of Infectious Disease. Burroughs Wellcome Fund. 2012-2017.
The immune pathogenesis of prenatal Listeria monocytogenes infection. Principle Investigator. National Institute of Allergy and Infectious Diseases (NIAID). 2012-2017. R01-AI100934.
Regulatory T cells dictate the immunity during persistent Salmonella infection. Principle Investigator. National Institute of Allergy and Infectious Diseases (NIAID). 2010-2015. R01-AI087830.
Ge Zhang, MD, PhD
Statistical genetics; population genetics
MD: West China University of Medical Sciences, Chengdu, China, 1997.
PhD: University of Cincinnati, Cincinnati, OH, 2007.
Karns R, Zhang G, Jeran N, Havas-Augustin D, Missoni S, Niu W, Indugula SR, Sun G, Durakovic Z, Narancic NS, et al. Replication of genetic variants from genome-wide association studies with metabolic traits in an island population of the Adriatic coast of Croatia. Eur J Hum Genet. 2011;19(3):341-6.
Zhang G, Karns R, Narancic NS, Sun G, Cheng H, Missoni S, Durakovic Z, Rudan P, Chakraborty R, Deka R. Common SNPs in FTO gene are associated with obesity related anthropometric traits in an island population from the eastern Adriatic coast of Croatia. PLoS One. 2010;5(4):e10375.
Nebert DW, Zhang G, Vesell ES. From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons, future directions. Drug Metab Rev. 2008;40(2):187-224.
Zhang G, Nebert DW, Chakraborty R, Jin L. Statistical power of association using the extreme discordant phenotype design. Pharmacogenet Genomics. 2006;16(6):401-13.
Martin TM, Zhang G, Luo J, Jin L, Doyle TM, Rajska BM, Coffman JE, Smith JR, Becker MD, Mackensen F, et al. A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease. Arthritis Rheum. 2005;52(1):269-74.
Zhang G, Luo J, Bruckel J, Weisman MA, Schumacher HR, Khan MA, Inman RD, Mahowald M, Maksymowych WP, Martin TM, et al. Genetic studies in familial ankylosing spondylitis susceptibility. Arthritis Rheum. 2004;50(7):2246-54.
Akey JM, Zhang G, Zhang K, Jin L, Shriver MD. Interrogating a high-density SNP map for signatures of natural selection. Genome Res. 2002;12(12):1805-14.
Zhang G, Zhang S, Chen W, Qiu W, Wu H, Wang J, Luo J, Gu X, Cotton RG. Go!Poly: A gene-oriented polymorphism database. Hum Mutat. 2001;18(5):382-7.
Assistant Professor, Maternal Fetal Medicine, University of Cincinnati College of Medicine
Associate Professor, Clinical Obstetrics and Gynecology, University of Cincinnati College of Medicine
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