Jeffrey A. Whitsett, MD
Title
Director, Perinatal Institute
Chief, Section of Neonatology, Perinatal and Pulmonary Biology
Appointment
Professor, University of Cincinnati College of Medicine
Email
jeff.whitsett@cchmc.org
Phone
513-636-4830
Fax
513-636-7868
Bio
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 clarifing 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, and the prestigious Daniel Drake Medal for scientific contributions from the University of Cincinnati College of Medicine.
Dr. Whitsett is the author of over 400 papers in both the basic science and clinical literature.
Dr. Whitsett's Profile
The Research Horizons article, "Mutations in Surfactant Proteins Cause Fatal Lung Diseases in Newborns and Children" profiles Dr. Whitsett and some of his research.
Credentials
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.
Awards and Honors
Research
- Cystic fibrosis research
- Lung morphogenesis
- Control of gene expression in the respiratory epithelium
- Gene delivery and therapy
Publications, Most Recent
Find more publications by Dr. Whitsett through PubMed
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. Human GM-CSF autoantibodies reproduce idiopathic pulmonary alveolar proteinosis in non-human primates. Submitted for publication.
Chen G, Korfhagen TR, Xu Y, Kitzmiller J, Wert SE, Maeda Y, Gregorieff A, Clevers H, Whitsett JA. SPDEF is required for pulmonary goblet cell differentiation and regulates a network of genes associated with mucous production. Submitted for publication.
Linnerth NM, Siwicky MD, Campbell CI, Watson KL, Petrik JJ, Whitsett JA, Moorehead RA. The type I insulin-like growth factor receptor induces pulmonary tumorigenesis. Submitted for publication.
Le Cras TD, Korfhagen TR, Davidson C, Schmidt S, Fenchel M, Ikegami M, Whitsett JA, Hardie WD. Inhibition of PI3K prevents transforming growth factor-alpha induced pulmonary fibrosis. Submitted for publication.
Lange AW, Keiser AR, Wells JM, Zorn AM, Whitsett JA. Sox17 promotes cell cycle progression and inhibits TGF-ß/Smad3 signaling to initiate progenitor cell behavior in the respiratory epithelium.PLoS One (In press).
Korfhagen TR, Le Cras TD, Davidson CR, Schmidt SM, Ikegami M, Whitsett JA, Hardie WD. Rapamycin prevents transforming growth factor-alpha induced pulmonary fibrosis.Am J Respir Cell Mol Biol (In press).
Lin W, Metzakopian E, Mavromatakis Y, Gao N, Balaskas N, Sasaki H, Briscoe J, Whitsett JA, Goulding M, Kaestner KH, Ang S-L. Foxa1 and Foxa2 function both upstream of and cooperatively with Lmx1a and Lmx1b in a feedforward loop promoting mesodisencephalic dopaminergic neuron development. Submitted for publication.
Kramer EL, Mushaben EM, Pastura PA, Acciani TH, Deutsch GH, Hershey GKK, Korfhagen TR, Hardie WD, Whitsett JA, Le Cras TD. Egr-1 suppresses EGFR-mediated airway hyperresponsiveness and lung remodeling in mice.Am J Respir Cell Mol Biol (In press).
Wang I-C, Meliton L, Ren X, Whitsett JA, Kalinichenko VV, Kalin TV. Deletion of forkhead box M1 transcription factor from lung epithelial cells inhibits pulmonary tumorigenesis. Submitted for publication.
Ikegami M, Grant S, Korfhagen T, Scheule RK, Whitsett JA. Surfactant protein-D regulates the postnatal maturation of pulmonary surfactant lipid pool sizes.J Appl Physiol 2009;106:1545-52.
Franks TJ, Colby TV, Travis WD, Tuder RM, Reynolds HY, Brody AR, Cardoso WV, Crystal RG, Drake CJ, Engelhardt J, Frid M, Herzog E, Mason R, Phan SH, Randell SH, Rose MC, Stevens T, Serge J, Sunday ME, Voynow JA, Weinstein BM, Whitsett J, Williams MC. Resident cellular components of the human lung: Current knowledge and goals for research on cell phenotyping and function.Proc Am Thorac Soc 2008;5:763-6.
Besnard V, Wert SE, Stahlman MT, Postle AD, Xu Y, Ikegami M, Whitsett JA. Deletion of Scap in alveolar type II cells influences lung lipid homeostasis and identifies a compensatory role for pulomonary lipofibroblasts.J Biol Chem 2009;284:4018-30.
Kalin TV, Wang I-C, Meliton L, Zhang Y, Wert SE, Ren X, Snyder J, Bell SM, Graf L, Whitsett JA, Kalinichenko VV. Forkhead box m1 transcription factor is required for perinatal lung function.Proc Natl Acad Sci 2008;105:19329-34.
Chaiworapongsa T, Hong J-S, Hull WM, Romero R, Whitsett JA. Amniotic fluid concentration of surfactant proteins in intra-amniotic infection.J Matern Fetal Neonatal Med 2008;21:663-70.
Chaiworapongsa T, Hong J-S, Hull WM, Kim CJ, Gomez R, Mazor M, Romero R, Whitsett JA. The concentration of surfactant protein-A in amniotic fluid decreases in spontaneous human parturition at term.J Matern Fetal Neonatal Med 2008;21:652-9.
Zhang Y, Goss AM, Cohen ED, Kadzik R, Lepore JJ, Muthukumaraswamy K, Yang J, DeMayo FJ, Whitsett JA, Parmacek MS, Morrisey EE. A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration.Nat Genet 2008;40:862-70.
Suzuki T, Sakagami T, Rubin BK, Nogee LM, Wood RE, Zimmerman SL, Smolarek T, Dishop MK, Wert SE, Whitsett JA, Grabowski G, Carey BC, Stevens C, van der Loo JCM, Trapnell BC. Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA.J Exp Med 2008;205:2703-10.
Kalin TV, Meliton L, Meliton AY, Zhu X, Whitsett JA, Kalinichenko VV. Pulmonary mastocytosis and enhanced lung inflammation in mice heterozygous null for the Foxf1 gene.Am J Respir Cell Mol Biol 2008;39:390-9.
Brandt EB, Mingler MK, Stevenson MD, Wang N, Hershey GKK, Whitsett JA, Rothenberg ME. Surfactant protein D alters allergic lung responses in mice and human subjects.J Allergy Clin Immunol 2008;121:1140-7.
Glasser SW, Senft AP, Whitsett JA, Maxfeld MD, Ross GF, Richardson TR, Prows DR, Xu Y, Korfhagen TR. Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice.J Immunol 2008;181:621-8.
Wan H, Luo F, Wert SE, Zhang L, Xu Y, Ikegami M, Maeda Y, Bell SM, Whitsett JA. Kruppel-like factor 5 is required for perinatal lung morphogenesis and function.Development 2008;135:2563-72.
Ikegami M, Weaver TE, Grant SN, Whitsett JA. Pulmonary surfactant surface tension influences alveolar capillary shape and oxygenation.Am J Respir Cell Mol Biol (In press).
Hardie WD, Davidson C, Ikegami M, Leikauf GD, Le Cras TD, Pestridge A, Whitsett JA, Korfhagen TR. EGF receptor tyrosine kinase inhibitors diminish transforming growth factor--induced pulmonary fibrosis.Am J Physiol 2008;294:L1217-25.
Kida H, Mucenski ML, Thitoff AR, Le Cras TD, Park K-S, Ikegami M, Müller W, Whitsett JA. GP130-STAT3 regulates epithelial cell migration and is required for repair of the bronchiolar epithelium.Am J Pathol 2008;172:1542-54.
Davé V, Wert SE, Tanner T, Thitoff AR, Loudy DE, Whitsett JA. Conditional deletion of Pten causes bronchiolar hyperplasia.Am J Respir Cell Mol Biol 2008;38:337-45.
Matsuzaki Y, Besnard V, Clark JC, Xu Y, Wert SE, Ikegami M, Whitsett JA. STAT3 regulates ABCA3 expression and influences lamellar body formation in alveolar type II cells.Am J Respir Cell Mol Biol 2008;38:551-8.
Ikegami M, Falcone A, Whitsett JA. STAT-3 regulates surfactant phospholipid homeostasis in normal lung and during endotoxin-mediated lung injury.J Appl Physiol 2008;104:15523-1760.
Bell SM, Schreiner CM, Wert SE, Mucenski ML, Scott WJ, Whitsett JA. R-spondin 2 is required for normal laryngeal-tracheal, lung, and limb morphogenesis.Development 2008;135:1049-58.
Quinton LJ, Jones MR, Robson BE, Simms BT, Whitsett JA, Mizgerd JP. Alveolar epithelial STAT3, IL-6 family cytokines, and host defense during Escherichia coli pneumonia.Am J Respir Cell Mol Biol 2008;38:699-706.
Yanagi S, Kishimoto H, Kawahara K, Sasaki T, Sasaki M, Nishio M, Yajima N, Hamada K, Horie Y, Kubo H, Whitsett JA, Mak TW, Nakano T, Nakazato M, Suzuki A. Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas in mice.J Clin Invest 2007;117:2929-40.
Tran PT, Fan AC, Bendapudi PK, Koh S, Komatsubara K, Chen J, Horng G, Bellovin DI, Giuriato S, Wang CS, Whitsett JA, Felsher DW. Combined inactivation of MYC and K-Ras oncogenes reverses tumorigenesis in lung adenocarcinomas and lymphomas.PLoS ONE 2008;3:e2125.
Besnard V, Xu Y, Whitsett JA. Sterol response element binding protein and thyroid transcription factor-1 (Nkx2.1) regulate Abca3 gene expression.Am J Physiol 2007;293:L1395-405.
Wedig KE, Whitsett JA. Down the Primrose Path: Petechiae in A Neonate Exposed to Herbal Remedy for Parturition.J Pediatr 2008;152:140.
Sun J, Chen H, Chen C, Whitsett JA, Mishina Y, Bringas P, Ma JC, Warburton D, Shi W. Prenatal epithelial cell-specific abrogation of Alk3-bone morphogenetic protein signaling causes neonatal respiratory distress by disrupting distal airway formation.Am J Pathol 2008;172:571-82.
Hardie WD, Korfhagen TR, Sartor MA, Prestridge A, Medvedovic M, Le Cras TD, Ikegami M, Wesselkamper SC, Davidson C, Dietsch M, Nichols W, Whitsett JA, Leikauf GD. Genomic profile of matrix and vasculature remodeling in TGF--induced pulmonary fibrosis.Am J Respir Cell Mol Biol 2007;37:309-21.
Maeda Y, Suzuki T, Pan X, Chen G, Pan S, Bartman T, Whitsett JA. CUL2 is required for the activity of hypoxia-inducible factor and vasculogenesis.J Biol Chem 2008;283:16084-92.
Ferri ALM, Lin W, Mavromatakis YE, Wang JC, Sasaki H, Whitsett JA, Ang S-L. Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner.Development 2007;134:2761-9.
Xu Y, Ikegami M, Wang Y, Matsuzaki Y, Whitsett JA. Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells.BMC Genomics 2007;8:455.
Yamamoto H, Yun EJ, Gerber H-P, Ferrara N, Whitsett JA, Vu TH. Epithelial-vascular cross talk mediated by VEGF-A and HGF signaling directs primary septae formation during distal lung morphogenesis.Dev Biol 2007;308:44-53.
Raj JR, Aliferis C, Caprioli RM, Cowley AW, Davies PF, Duncan MW, Erle DJ, Erzurum SC, Finn PW, Ischiropoulos H, Kaminski N, Kleeberger SR, Leikauf GD, Loyd JE, Martin TR, Matalon S, Moore JH, Quackenbush J, Sabo-Attwood T, Shapiro SD, Schnitzer JE, Schwartz DA, Schwiebert LM, Sheppard D, Ware LB, Weiss ST, Whitsett JA, Wurfel MM, Matthay MA. Genomics and proteomics of lung disease: Conference summary. Am J Physiol 2007;293:L45-51.
Saugstad OD, Hansen TWR, Rønnestad A, Nakstad B, Tølløfsrud PA, Reinholt F, Hamvas A, Cole FS, Dean M, Wert SE, Whitsett JA, Nogee LM. Novel mutations in the gene encoding ATP binding cassette protein member A3 (ABCA3) resulting in fatal neonatal lung disease.Acta Pædiatrica 2007;96:185-90.
Ikegami M, Scoville EA, Grant S, Korfhagen T, Brondyk W, Scheule RK, Whitsett JA. Surfactant protein-D and surfactant inhibit endotoxin-induced pulmonary inflammation.Chest 2007;132:1447-54.
Senft AP, Korfhagen TR, Whitsett JA, LeVine AM. Surfactant protein D regulates the cell surface expression of alveolar macrophage ß2-integrins.Am J Physiol 2007;292:L469-75.
Prestridge A, Wooldridge J, Deutsch G, Young LR, Wert SE, Whitsett JA, Nogee L. Persistent tachypnea and hypoxia in a 3-month-old term infant.J Pediatr 2006;149:702-6.
Wedig KE, Kogan J, Schorry EK, Whitsett JA. Skeletal demineralization and fractures caused by fetal magnesium toxicity.J Perinatol 2006;26:371-4.
Park K-S, Korfhagen TR, Bruno MD, Kitzmiller JA, Wan H, Wert SE, Hershey GKK, Chen G, Whitsett JA. SPDEF regulates goblet cell hyperplasia in the airway epithelium.J Clin Invest 2007;117:978-88.
Tichelaar JW, Wesselkamper SC, Chowdhury S, Yin H, Berclaz PY, Sartor MA, Leikauf GD, Whitsett JA. Duration-dependent cytoprotective versus inflammatory effects of lung epithelial fibroblast growth factor-7 expression.Exp Lung Res 2007;33:385-417.
Bry K, Whitsett JA, Lappalainen U. IL-1ß disrupts postnatal lung morphogenesis in the mouse.Am J Respir Cell Mol Biol 2007;36:32-42.
Stahlman MT, Besnard V, Wert SE, Weaver TE, Dingle S, Xu Y, von Zychlin K, Olson SJ, Whitsett JA. Expression of ABCA3 in developing lung and other tissues.J Histochem Cytochem 2007;55:71-83.
Special Interests
Dr. Jeffrey Whitsett's laboratory seeks to:
- Elucidate the hierarchy of transcriptional controls and signaling cascades which determine commitment of progenitor cells that produce the differentiated epithelial cells lining the primordial and mature respiratory tract
- Determine mechanisms controlling cell-specific gene transcription governing lung epithelial cell proliferation and differentiation that will provide insight into the pathogenesis of acute and chronic lung disorders such as respiratory distress syndrome, pulmonary fibrosis, bronchopulmonary dysplasia and other disorders of surfactant homeostasis
Transcriptional control of surfactant expression, lung morphogenesis and function are being assessed. Conditional systems for gene targeting and addition have been developed for study of lung formation, and function, as well as for identifying lung progenitor cells and their fates in the mouse. Transgenic mouse models are being utilized to understand the pathogenesis of genetic and inflammatory lung disorders and to develop gene therapy for respiratory disease. The role of surfactant in innate host defense and lung function is studied.
Visit the Whitsett Lab in the Division of Pulmonary Biology.
Section Chief
