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Jeffrey A. Whitsett, MD Co-Director, Perinatal Institute
Co-Director, Perinatal Institute
Chief, Section of Neonatology, Perinatal and Pulmonary Biology
Professor, UC Department of Pediatrics
Cystic fibrosis research; lung morphogenesis; control of gene expression in the respiratory epithelium; gene delivery and therapy
Visit the Whitsett Lab.
Jeffrey A. Whitsett, MD, is chief of the Section of Neonatology, Perinatal and Pulmonary Biology at Cincinnati Children's Hospital Medical Center.
Dr. Whitsett received his medical degree from Columbia University, in New York, and has been a faculty member since 1977. He is internationally known for his research in pulmonary medicine, as well as for his clinical expertise in neonatology.
Dr. Whitsett has made a series of groundbreaking contributions in pulmonary medicine. His major pioneering work has been on surfactant proteins A, B, C and D, cloning their genes, and clarifying their roles in lung development.
Throughout his career, Dr. Whitsett has had the remarkable ability to move from molecular biology, to animal models, to diagnosis and therapy of human disease. He played a critical role in making surfactant protein replacement a routine tool for treating immature lungs and respiratory distress syndrome in premature infants. His laboratory has contributed to the identification of a number of genes critical for lung formation and function. Mutations in genes regulating surfactant homeostasis were shown to cause acute and chronic lung disease in infants and adults.
Dr. Whitsett is a member of the Institute of Medicine, National Academy of Sciences and is the recipient of the Mead Johnson Award, a National Institutes of Health (NIH) Merit Award, the first Julius Comroe Lectureship in Pulmonary Research from FASEB, the William Cooper Procter Award from Cincinnati Children's, the Amberson Lecture Award of the American Thoracic Society, the prestigious Daniel Drake Medal for scientific contributions from the University of Cincinnati College of Medicine, the International Arvo Ylppö Medal from the Finnish Foundation for Pediatric Research and the Grand Hamdan International Award on Neonatal Medicine from the United Arab Emirates.
Dr. Whitsett is the author of more than 400 papers in both the basic science and clinical literature.
MD: Columbia University, New York, NY, 1973.
Residency: Pediatrics, Mt. Sinai Hospital, New York City, 1974 to 1976.
Fellowship: Neonatology, Children's Hospital Medical Center, University of Cincinnati College of Medicine, 1976 to 1977.
Sivaprasad U, Askew DJ, Ericksen MB, Gibson AM, Stier MT, Brandt EB, Bass SA, Daines MO, Chakir J, Stringer KF, Wert SE, Whitsett JA, Le Cras TD, Wills-Karp M, Silverman GA, Khurana Hershey GK. A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma. J Allergy Clin Immunol. 2011 Jan;127(1):254-61, 261.e1-6.
Lin SC, Wani MA, Whitsett JA, Wells JM. Klf5 regulates lineage formation in the pre-implantation mouse embryo. Development.2010 Dec;137(23):3953-63.
Suzuki T, Sakagami T, Young LR, Carey BC, Wood RE, Luisetti M, Wert SE, Rubin BK, Kevill K, Chalk C, Whitsett JA, Stevens C, Nogee LM, Campo I, Trapnell BC. Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. Am J Respir Crit Care Med. 2010 Nov 15;182(10):1292-304.
Wang IC, Zhang Y, Snyder J, Sutherland MJ, Burhans MS, Shannon JM, Park HJ, Whitsett JA, Kalinichenko VV. Increased expression of FoxM1 transcription factor in respiratory epithelium inhibits lung sacculation and causes Clara cell hyperplasia. Dev Biol. 2010 Nov 15;347(2):301-14.
Perl AK, Riethmacher D, Whitsett JA. Conditional Depletion of Airway Progenitor Cells Induces Peribronchiolar Fibrosis. Am J Respir Crit Care Med. 2010 Sep 24.
Tompkins DH, Besnard V, Lange AW, Keiser AR, Wert SE, Bruno MD, Whitsett JA. Sox2 Activates Cell Proliferation and Differentiation in the Respiratory Epithelium. Am J Respir Cell Mol Biol. 2010 Sep 20.
Meyer SE, Hasenstein JR, Baktula A, Velu CS, Xu Y, Wan H, Whitsett JA, Gilks CB, Grimes HL. Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival. Am J Pathol. 2010 Sep;177(3):1503-13.
Xu Y, Zhang M, Wang Y, Kadambi P, Dave V, Lu LJ, Whitsett JA. A systems approach to mapping transcriptional networks controlling surfactant homeostasis. BMC Genomics. 2010 Jul 26;11:451.
Sakagami T, Beck D, Uchida K, Suzuki T, Carey BC, Nakata K, Keller G, Wood RE, Wert SE, Ikegami M, Whitsett JA, Luisetti M, Davies S, Krischer JP, Brody A, Ryckman F, Trapnell BC. Patient-derived granulocyte/macrophage colony-stimulating factor autoantibodies reproduce pulmonary alveolar proteinosis in nonhuman primates. Am J Respir Crit Care Med. 2010 Jul 1;182(1):49-61.
Chen G, Wan H, Luo F, Zhang L, Xu Y, Lewkowich I, Wills-Karp M, Whitsett JA. Foxa2 programs Th2 cell-mediated innate immunity in the developing lung. J Immunol. 2010 Jun 1;184(11):6133-41.
Shawn K. Ahlfeld, MD
investigates the effects of neonatal lung injury on alveolar repair and development. Using developmentally-relevant genetic and physiologic approaches, he is identifying the role of interstitial fibroblasts in mechanisms behind alveolar simplification characteristic of bronchopulmonary dysplasia, with the long-term goal of developing novel therapies that promote normal alveolar lung development and function.
Assistant Professor, UC Department of Pediatrics
Neonatal-perinatal medicine; bronchopulmonary dysplasia
As a neonatal fellow and junior faculty, Dr. Ahlfeld has evaluated the role of matricellular proteins in saccular and early alveolar lung development. He and his team has determined that hyperoxia exposure resulted in the mis-expression of the Transforming Growth Factor Beta (TGFβ)-responsive extracellular matrix protein, periostin, during critical periods of saccular-alveolar lung development. Periostin proved to be a novel marker for both normal myofibroblastic activity during alveolarization and abnormal myofibroblastic persistence during late fibrotic stages of lung injury.
Under a scholar grant through the Prematurity and Respiratory Outcomes Program (PROP), they have demonstrated, for the first time, that plasma periostin levels in extremely premature infants during the first weeks of age correlate with the development and severity of BPD. Their investigations into TGFβ superfamily signaling during saccular and alveolar lung development, as well as its role in BPD pathogenesis, are ongoing.
Contrary to the prevailing notion of up-regulation, TGFβ extracellular signaling ligands, intracellular signaling messengers, and down-stream signaling targets are all down-regulated during early hyperoxic lung injury. They have determined that TGFβ down-regulation coincides with a period of saccular-alveolar lung development that is critical for development of distal lung complexity and function. The down-regulation of TGFβ signaling during this critical window of lung development occurs well before the up-regulation of TGFβ signaling associated with chronic hyperoxic lung injury that they and others have described.
Additionally, his team has identified that a second matricellular protein, TGFβ-induced protein (TGFBI), is a novel extracellular matrix protein mis-expressed by neonatal hyperoxia and vital for normal alveolar development.
Their findings have provided new mechanistic targets in BPD pathogenesis and have challenged the paradigm related to the role of TGFβ up-regulation in neonatal lung injury.
MD: Indiana University School of Medicine, Indianapolis, IN, 2005.
Residency: Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.
Fellowship: Neonatal-Perinatal Medicine, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.
Certification: General Pediatrics, 2008; Neonatal and Perinatal Medicine, 2012.
Ahlfeld SK, Wang J, Gao Y, Snider P, Conway SJ. Initial suppression of transforming growth factor-β signaling and loss of TGFBI causes early alveolar structural defects resulting in bronchopulmonary dysplasia. Am J Pathol. 2016.
Goss KN, Tepper RS, Lahm T, Ahlfeld SK. Increased Cardiac Output and Preserved Gas Exchange Despite Decreased Alveolar Surface Area in Rats Exposed to Neonatal Hyperoxia and Adult Hypoxia. Am J Respir Cell Mol Biol. 2015;53(6):902-6.
Goss KN, Cucci AR, Fisher AJ, Albrecht M, Frump A, Tursunova R, Gao Y, Brown MB, Petrache I, Tepper RS, *Ahlfeld SK, *Lahm T. Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure. Am J Physiol Lung Cell Mol Physiol. 2015 Apr 15;308(8):L797-806. (* co-senior authorship).
Assaf SJ, Chang DV, Tiller CJ, Kisling JA, Case J, Mund JA, Slaven JE, Yu Z, Ahlfeld SK, Poindexter B, Haneline LS, Ingram DA, Tepper RS. Lung Parenchymal Development in Premature Infants without Bronchopulmonary Dysplasia. Pediatr Pulmonol. 2015;50(12):1313-9.
Beam K, Aliaga S, Ahlfeld S, Cohen-Wolkowiez M, Smith P, Laughon M. A systematic review of randomized controlled trials for the prevention of bronchopulmonary dysplasia in infants. J Perinatol. 2014;34(9):705-10.
Ahlfeld SK, Gao Y, Conway SJ, Tepper RS. Relationship of Structural to Functional Impairment during Alveolar-Capillary Membrane Development. Am J Pathol. 2015;185(4):913-9.
Ahlfeld SK, Conway SJ. Assessment of Inhibited Alveolar-Capillary Membrane Structural Development and Function in Bronchopulmonary Dysplasia. Birth Defects Res A Clin Mol Teratol. 2014;100(3):168-79.
Ahlfeld SK, Gao Y, Wang J, Horgusluoglu E, Bolanis E, Clapp DW, Conway SJ. Periostin down-regulation is an early marker of inhibited neonatal murine lung alveolar septation. Birth Defects Res A Clin Mol Teratol. 2013;97(6):373-85.
Ahlfeld SK, Conway SJ. Aberrant signaling pathways of the lung mesenchyme and their contributions to the pathogenesis of bronchopulmonary dysplasia. Birth Defects Res A Clin Mol Teratol. 2012;94(1):3-15.
Sehra S, Yao W, Nguyen ET, Ahyi AN, Barbé Tuana FM, Ahlfeld SK, Snider P, Tepper RS, Petrache I, Conway SJ, Kaplan MH. Periostin regulates goblet cell metaplasia in a model of allergic airway inflammation. J Immunol. 2011;186(8):4959-66.
Hitesh Deshmukh, MD, PhD
and his laboratory focuses on the role of intestinal commensal bacteria in development of appropriate innate immune responses to pathogens in neonates. The ultimate goal of this research is to develop novel therapeutic approaches to decrease mortality in premature babies, one of the most vulnerable groups.
MB; BS: University of Mumbai, Mumbai, India, 2001.
PhD: University of Cincinnati, Cincinnati, OH, 2006.
Residency: Pediatrics, State University of New York at Buffalo, Buffalo, NY, 2011.
Fellowship: Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, 2014.
Certification: American Board of Pediatrics, 2012.
Deshmukh HS, Liu Y, Menkiti OR, Mei J, Dai N, O'Leary CE, et al. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nature Medicine. 2014 Apr 20.
Yan QS, Sharma-Kuinkel BK, Deshmukh HS, Tsalik EL, Cr DD, Lucas JA et al. Dusp3 and Psme3 Are Associated with Murine Susceptibility to Staphylococcus aureus Infection and Human Sepsis. Plos Pathogens. 2014 Jun 5;10(6).
Deshmukh HS, Lioy J. The use of early lung biopsy in detection of fatal pulmonary disease in the neonate. The Journal of Pediatrics. 2014 Apr;164(4):934-6.
Deshmukh HS, Caty MG, Ryan RM, Lakshminrusimha S. Intermittent 'bulge' in the umbilical cord. Journal of Perinatology. 2010 Jul;30(7):500-2.
Ahn SH, Deshmukh HS8, Johnson N, Cowell LG, Rude TH, Scott WK, et al. Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses. PLoS Pathogens. 2010;6(9):e1001088. *co-first author.
Deshmukh HS, McLachlan A, Atkinson JJ, Hardie WD, Korfhagen TR, Dietsch M, et al. Matrix metalloproteinase-14 mediates a phenotypic shift in the airways to increase mucin production. American Journal of Respiratory and Critical Care Medicine. 2009 Nov 1;180(9):834-45.
Deshmukh HS, Hamburger JB, Ahn SH, McCafferty DG, Yang SR, Fowler VG, Jr. Critical role of NOD2 in regulating the immune response to Staphylococcus aureus. Infection and immunity. 2009 Apr;77(4):1376-82.
Deshmukh HS, Shaver C, Case LM, Dietsch M, Wesselkamper SC, Hardie WD, et al. Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production. American Journal of Respiratory Cell and Molecular Biology. 2008 Apr;38(4):446-54.
Campbell SJ, Deshmukh HS*, Nelson CL, Bae IG, Stryjewski ME, Federspiel JJ, et al. Genotypic characteristics of Staphylococcus aureus isolates from a multinational trial of complicated skin and skin structure infections. Journal of Clinical Microbiology. 2008 Feb;46(2):678-84. *co-first author.
Deshmukh HS, Case LM, Wesselkamper SC, Borchers MT, Martin LD, Shertzer HG, et al. Metalloproteinases mediate mucin 5AC expression by epidermal growth factor receptor activation. American Journal of Respiratory and Critical Care Medicine. 2005 Feb 15;171(4):305-14.
Alan H. Jobe, MD, PhD Director, Division of Perinatal Biology
has a special research focus on surfactant physiology. Dr. Jobe is also interested in lung maturation and lung injury in the fetus and newborn, the use of antenatal corticosteroids, and lung injury with ventilation of the preterm infant.
Director, Division of Perinatal Biology
Clinical trials in neonatology; bronchopulmonary dysplasia
MD: University of California, San Diego, CA, 1973.
PhD: University of California, San Diego, CA, 1973.
Residency: University Hospital, University of California, San Diego, CA, 1974 to 1975.
Fellowship: University of California, San Diego, CA, 1975 to 1977.
Board Certified: Pediatrics and Neonatal-Perinatal Medicine.
Moss TJM, Nitsos I, Knox CL, Polglase GR, Kallapur SG, Ikegami M, Jobe AH, Newnham JP. Ureaplasma colonization of amniotic fluid and efficacy of antenatal corticosteroids for preterm lung maturation in sheep. AJOG. 2009;200(1):96.e1-6.
Polglase GR, Hillman NH, Ball MK, Kramer BW, Kallapur SG, Jobe AH, Pillow JJ. Lung and systemic inflammation in preterm lambs on CPAP or conventional ventilation. Pediatr Res. 2009;65(1):67-71.
Cheah F-C, Pillow JJ, Kramer BW, Polglase GR, Nitsos I, Newnham JP, Jobe AH, Kallapur SG. Airway inflammatory cell responses to intra-amniotic lipopolysaccharide in a sheep model of chorioamnionitis. Am J Physiol Lung Cell Mol Physiol. 2008;296:L384-93.
Ball MK, Jobe AH, Polglase GR, Kallapur SG, Choe-Cheah F, Hillman NH, Pillow JJ. High and low body temperature during the initiation of ventilation for near-term lambs. Resuscitation. 2008;80:133-7.
Kramer BW, Albertine KH, Moss TJM, Nitsos I, Speer CP, Newnham JP, Jobe AH. All-trans retinoic acid does not modulate intra-amniotic endotoxin mediated effects on the fetal sheep lung. The Anatomical Record. 2008;291:1271-7.
Polglase GR, Hillman NH, Pillow JJ, Cheah F-C, Nitsos I, Moss TJ, Kramer BW, Ikegami M, Kallapur SG, Jobe AH. Positive end-expiratory pressure and tidal volume during initial ventilation of preterm lambs. Pediatr Res. 2008;64:517.
Hillman N, Moss TJM, Nitsos I, Kramer BW, Bachurski C, Ikegami M, Jobe AH, Kallapur SG. Toll-like receptors and agonist responses in the developing fetal sheep lung. Pediatr Res. 2008;63:388-93.
Sweet DG, Huggett MT, Warner JA, Moss TJM, Halliday HL, Newnham JP, Kallapur SG, Jobe AH, Kramer BW. Maternal betamethasone and chorioamnionitis induce different collagenases and lung maturation in fetal sheep lungs. Neonatology. 2008;94:79-86.
Jobe AH, Moss TJM, Nitsos Il, Ikegami M, Kallapur SG, Newnham JP. Betamethasone for lung maturation: testing dose and formulation in fetal sheep. AJOG. 2007;197:523.
Moss TJM, Knox CL, Kallapur SG, Nitsos I, Theodoropoulos C, Ikegami M, Newnham JP, Jobe AH. Experimental amniotic fluid infection in sheep: effects of Ureaplasma parvum serovars 3 and 6 on preterm or term fetal sheep. Am J Ob Gyn. 2008;198:122e18.
Suhas G. Kallapur, MD Director, Neonatology Continuing Medical Education
Director, Neonatology Continuing Medical Education
Global Health Center
Chorioamnionitis; bronchopulmonary dysplasia; respiratory distress syndrome; fetal immunity
MBBS: University of Bombay, India, 1984.
DCH: College of Physicians and Surgeons, Bombay, India, 1986.
MD, Pediatrics: University of Bombay, India, 1986.
Residency: University of Bombay, India, 1984-87.
Residency: Children's Hospital of Michigan, Detroit, MI, 1988-90.
Fellowship: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 1990-1993.
Kemp MW, Kallapur SG, Jobe AH, Newnham JP. Obesity and the developmental origins of health and disease. J Paediatr Child Health. 2011 Jan 18.
Morrow AL, Meinzen-Derr J, Huang P, Schibler KR, Cahill T, Keddache M, Kallapur SG, Newburg DS, Tabangin M, Warner BB, Jiang X. Fucosyltransferase 2 Non-Secretor and Low Secretor Status Predicts Severe Outcomes in Premature Infants. J Pediatr. 2011 May;158(5):745-51.
Hillman NH, Kallapur SG, Pillow JJ, Nitsos I, Polglase GR, Ikegami M, Jobe AH. Inhibitors of inflammation and endogenous surfactant pool size as modulators of lung injury with initiation of ventilation in preterm sheep. Respir Res. 2010 Oct 29;11:151.
Shah TA, Hillman NH, Nitsos I, Polglase GR, Pillow JJ, Newnham JP, Jobe AH, Kallapur SG. Pulmonary and systemic expression of monocyte chemotactic proteins in preterm sheep fetuses exposed to lipopolysaccharide-induced chorioamnionitis. Pediatr Res. 2010 Sep;68(3):210-5.
Shah TA, Hillman NH, Nitsos I, Polglase GR, Pillow JJ, Newnham JP, Jobe AH, Kallapur SG. Pulmonary and Systemic Expression of Monocyte Chemotactic Proteins in Preterm Sheep Fetuses Exposed to LPS Induced Chorioamnionitis. Pediatr Res. 2010 May 28.
Jobe AH, Kallapur SG. Long term consequences of oxygen therapy in the neonatal period. Semin Fetal Neonatal Med. 2010 Aug;15(4):230-5.
Hillman NH, Pillow JJ, Ball MK, Polglase GR, Kallapur SG, Jobe AH. Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep. Respir Res. 2009 Dec 15;10:124.
Hillman NH, Kallapur SG, Pillow JJ, Moss TJ, Polglase GR, Nitsos I, Jobe AH. Airway injury from initiating ventilation in preterm sheep. Pediatr Res. 2010 Jan;67(1):60-5.
Jobe AH, Nitsos I, Pillow JJ, Polglase GR, Kallapur SG, Newnham JP. Betamethasone dose and formulation for induced lung maturation in fetal sheep. Am J Obstet Gynecol. 2009 Dec;201(6):611.e1-7.
Kallapur SG, Moss TJ, Auten RL Jr, Nitsos I, Pillow JJ, Kramer BW, Maeda DY, Newnham JP, Ikegami M, Jobe AH. IL-8 signaling does not mediate intra-amniotic LPS-induced inflammation and maturation in preterm fetal lamb lung. Am J Physiol Lung Cell Mol Physiol. 2009 Sep;297(3):L512-9.
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