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Jeffrey A. Whitsett, MD

Co-Director, Perinatal Institute

Chief, Section of Neonatology, Perinatal and Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-2790

Fax 513-636-7868

Email jeffrey.whitsett@cchmc.org

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Specialties

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Cystic fibrosis research; lung morphogenesis; control of gene expression in the respiratory epithelium; gene delivery and therapy

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Biography

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Dr. Whitsett's laboratory discovered surfactant proteins B and C, cloned the genes encoding the surfactant proteins A, B, C, and D, Scgb1a1, TTF-1 and others and utilized transgenic mouse models to delete and mutate these genes in transgenic mice. They identified transcriptional networks regulating lung morphogenesis and perinatal lung maturation contributing to the understanding of the roles of TTF-1, CEBPα, SOX2, SOX17, FOXA1, FOXA2, FOXA3, SPDEF, KLF5, CDC42 and others using both in vitro and in vivo methods. They identified multiple transcription factors regulating goblet cell differentiation airway epithelial cells including critical role of SPDEF, FOXA3 and airway goblet cells controlling innate immunity. They produced transgenic mouse models for conditional deletion and expression of genes involved in lung development, disease, and repair. They have generated transgenic models of pulmonary adenocarcinoma and explored the role of transcription factors mediating pulmonary adenocarcinoma in vivo and in vitro. They utilized RNA-Seq, microarray, Chip-Seq in the application of Nex-Gen sequencing and bioinformatics to identify and understand networks involved in the regulation of lung development and disease using clinical sample, as well as in vitro and in vivo models.

Dr. Whitsett has a long interest in training both in the clinical setting in “Neonatology” and in “Pulmonary Biology” and has contributed to the direct training of more than 80 graduate or post-graduate students in his laboratory. The scope of his work is represented in several recent reviews. Initial discoveries from his laboratory provided early insights into the genes and proteins critical for surfactant function including ABCA3, SFTPC, SFTPB, SFTPA, SFTPD.

Education and Training

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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.

Publications

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View PubMed Publications

Davies ER, Kelly JFC, Howarth PH, Wilson DI, Holgate ST, Davies DE, Whitsett JA, Haitchi HM. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life. JCI Insight. 2016;1:e87632.

Ustiyan V, Zhang Y, Perl A-KT, Whitsett JA, Kalin TV, Kalinichenko VV. ß-Catenin and Kras/Foxm1 Signaling Pathway are Critical to Restrict Sox9 in Basal Cells During Pulmonary Branching Morphogenesis. Dev Dyn. 2016;245:590-604.

Guo M, Wang H, Potter SS, Whitsett JA, Xu Y. SINCERA: A pipeline for single-cell RNA-Seq profiling analysis. PLoS Comput Biol. 2015;11:e1004575.

Kamath-Rayne BD, Du Y, Hughes M, Wagner EA, Muglia LJ, DeFranco EA, Whitsett JA, Salomonis N, Xu Y. Systems biology evaluation of cell-free amniotic fluid transcriptome of term and preterm infants to detect fetal maturity. BMC Med Genomics. 2015;8:67.

Du Y, Guo M, Whitsett JA, Xu Y. ‘LungGENS’: a web-based tool for mapping single-cell gene expression in the developing lung. Thorax. 2015;70:1092-1094.

Snowball J, Ambalavanan M, Whitsett J, Sinner D. Endodermal Wnt signaling is required for tracheal cartilage formation. Dev Biol. 2015;405:56-70.

Wakata K, Tsuchiya T, Tomoshige K, Takagi K, Yamasaki N, Matsumoto K, Miyazaki T, Nanashima A, Whitsett JA, Maeda Y, Nagayasu T. A favorable prognostic marker for EGFR mutant non-small cell lung cancer: immunohistochemical analysis of MUC5B. BMJ Open. 2015;5:e008366.

Ishida N, Fukazawa T, Maeda Y, Yamatsuji T, Kato K, Matsumoto K, Shimo T, Takigawa N, Whitsett JA, Naomoto Y. A novel P13K inhibitor iMDK suppresses non-small cell lung Cancer cooperatively with a MEK inhibitor. Exp Cell Res. 2015;335:197-206.

Rajavelu P, Chen G, Xu Y, Kitzmiller JA, Korfhagen TR, Whitsett JA. Airway epithelial SPDEF integrates goblet cell differentiation and pulmonary Th2 inflammation. J Clin Invest. 2015;125:2021-2031.

Snowball J, Ambalavanan M, Cornett B, Lang R, Whitsett J, Sinner D. Mesenchymal Wnt signaling promotes formation of sternum and thoracic body wall. Dev Biol. 2015;401:264-275.

Grants

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Airway Progenitor Cell Proliferation and Differentiation During Lung Repair. Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Jan 2012-Dec 2016. U01HL110964.

Transcriptional Programming of Asthma Related Pathology in Respiratory Epithelia. Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Apr 2013-Mar 2018. 2 R01HL095580.

Omics of Lung Diseases. Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Sep 2013-May 2018. K12 HL119686.

“Lung Map” Atlas Research Center. Multiple Principal Investigators. National Institutes Health/National Heart, Lung, and Blood Institute. Jun 2014-Apr 2019. U01 HL122642.

Editing Alveolar Progenitor Cells for Correction of Monogenic Disease. Program Director/Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Sep 2016-Aug 2023. U01 HL134745.

Role of EMC3/TMEM111 in Alveolar Epithelial Cell Function. Program Director/Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Apr 2017-Mar 2022. R01 HL136722.

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