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Giants in Chest Medicine |

Giants in Chest MedicineGiants in Chest Medicine: Jay A. Nadel, MD FREE TO VIEW

Arthur F. Gelb, MD, FCCP
Author and Funding Information

Arthur F. Gelb, MD, FCCP, is Clinical Professor of Medicine, Geffen School of Medicine at the University of California, Los Angeles, Medical Center; and Chair, Pulmonary Diseases, Lakewood Regional Medical Center, Lakewood, CA.

CORRESPONDENCE TO: Arthur F. Gelb, MD, FCCP, Lakewood Regional Medical Center, 3650 E South St, Ste 308, Lakewood, CA 90712; e-mail: afgelb@msn.com


Editor’s Note: This series recognizes and highlights the accomplishments of individuals who have contributed greatly to chest medicine. To watch the interview with Dr Nadel, go to journal.publications.chestnet.org

FINANCIAL/NONFINANCIAL DISCLOSURES: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

ADDITIONAL INFORMATION: See video interview of Dr Nadel online at http://dx.doi.org/10.1378/chest.14-2901.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(4):880-882. doi:10.1378/chest.14-2901
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Published online

I thank Richard S. Irwin, MD, Master FCCP, and Editor in Chief, CHEST, for offering me the opportunity to profile Jay A. Nadel, MD, a giant in chest medicine. Born in 1929 in Philadelphia, Pennsylvania, Dr Nadel received his MD degree from Jefferson Medical College in 1953. During his internship and residency in cardiology at Philadelphia General Hospital (1953-1956), Dr Nadel met Julius Comroe, MD, who headed the Graduate School at the University of Pennsylvania. Subsequently, Dr Nadel spent 2 years in the US Air Force (Travis Air Force Base) near San Francisco, California, and Dr Comroe was recruited to head the Cardiovascular Research Institute at the University of California, San Francisco (UCSF). In 1958, Dr Nadel was chosen to be Dr Comroe’s research fellow.

Giants in Chest Medicine: Jay A. Nadel, MD

Running Time: 19:28

Dr Nadel’s first research showed the deleterious effects of cigarette smoke in the airways. In 1962, he was a visiting scientist in Oxford, England. After returning to UCSF, Dr Nadel’s experience with London fog drove him to investigate the deleterious effects of air pollutants, focusing on ozone and sulfur dioxide. These studies became the basis of the laws limiting these pollutants in California and, subsequently, the basis of the US national standards. Dr Nadel was awarded one of the early A. P. Giannini Foundation fellowships to perform this air pollution research.

Professors Comroe and Holly Smith, MD, chair of Medicine at UCSF, quickly recognized Dr Nadel’s genius for problem solving and leadership and appointed him the first chief of the Division of Pulmonary Diseases. He became professor of Medicine in 1970, Radiology in 1974, and Physiology in 1976.

Dr Nadel’s early work on inhaled irritants, cigarette smoke, and air pollutants drew his attention to the relationship between the environment, which is the source of inhaled particulates that act as “invaders” (viruses, bacteria, smoke, pollutants, allergens, other irritants) and the lungs, which “defend” the host. Dr Nadel realized that the battle between environmental invaders and lung defenders must begin at the lung epithelial luminal surfaces, especially in airways. Thus, viruses depositing on the luminal surface must enter the epithelial cells to multiply, so we must pay attention to the luminal (invading) surface of the epithelium. In the early days of cell and molecular biology, Dr Nadel focused his attention on the airway epithelial cells, a major target for the deposition of invading particulates. This continuing focus led him and his colleagues to discover important proinflammatory and antiinflammatory signaling pathways. Further, the Nadel group described other signaling pathways, some of which exaggerate the inflammatory responses and others that inhibit them. These interactions provide important strategies for future studies of the interactions of signaling pathways such as epidermal growth factor receptor, epithelial interferon signaling, and the cystic fibrosis transmembrane conductance regulator (the molecule whose absence is responsible for cystic fibrosis).

From 1977 to 2012, Dr Nadel was the director of the UCSF National Institutes of Health Multidisciplinary Pulmonary Research Training Program. Pulmonary academicians throughout the world have trained under his leadership, including approximately 150 in his own laboratory. In appreciation of his many accomplishments, the University of Paris awarded him the René Descartes Medal. He has honorary degrees in medicine and law. In the laboratory, Dr Nadel works directly with each trainee. It is his belief that one senior scientist together with a single trainee can accomplish more than five researchers working alone!

As president of the American Thoracic Society, Dr Nadel successfully lobbied Congress to change the name of the National Heart Institute to the National Heart and Lung Institute. This change helped finance the development of lung research. The designation of pulmonology as a subspecialty followed. He also assisted in lobbying the National Institutes of Health for 5-year grants to be awarded to young pulmonary investigators. These awards provided the means for departments of medicine throughout the country to develop Lung Divisions.

When he was asked what keeps him in teaching and research at the age of 85, Dr Nadel said, “First of all, I have loved UCSF because of its history of open communication. When I arrived at UCSF in 1958, we were the 85th best medical school in the [United States]. Now we are tops. Second, as a trained physician and scientist, I have had the special opportunity to perform research at both the basic and clinical levels, and I have benefited from the opportunity to help integrate basic science and clinical pulmonary medicine.”

That reminded him to mention an important personal adventure: Together with John Murray, MD, esteemed as a world-famous pulmonologist, Dr Nadel coauthored the Textbook of Respiratory Medicine in the 1980s. In the textbook, the authors have made a special effort to integrate science and bedside medicine. It is now in its sixth edition, with constantly upgraded content and improved readability. Finally, Dr Nadel thanks the many colleagues who have added to the excitement of his life.

Nadel JA, Comroe JH Jr. Acute effects of inhalation of cigarette smoke on airway conductance. J Appl Physiol. 1961;16:713-716.
 
Nadel JA, Salem H, Tamplin B, Tokiwa Y. Mechanism of bronchoconstriction during inhalation of sulfur dioxide. J Appl Physiol. 1965;20:164-167.
 
Gold WM, Kaufman HS, Nadel JA. Elastic recoil of the lungs in chronic asthmatic patients before and after therapy. J Appl Physiol. 1967;23(4):433-438.
 
Nadel JA, Gold WM, Burgess JH. Early diagnosis of chronic pulmonary vascular obstruction. Value of pulmonary function tests. Am J Med. 1968;44(1):16-25.
 
Goldsmith JR, Nadel JA. Experimental exposure of human subjects to ozone. J Air Pollut Control Assoc. 1969;19(5):329-330.
 
Nadel JA, Wolfe WG, Graf PD, et al. Powdered tantalum. N Engl J Med. 1970;283(6):281-286.
 
Nadel JA, Cabezas GA, Austin JHM. In vivo roentgenographic examination of parasympathetic innervation of small airways. Use of powdered tantalum and a fine focal spot x-ray tube. Invest Radiol. 1971;6(1):9-17.
 
Gelb AF, Gold WM, Wright RR, Bruch HR, Nadel JA. Physiologic diagnosis of subclinical emphysema. Am Rev Respir Dis. 1973;107(1):50-63.
 
Olver RE, Davis B, Marin MG, Nadel JA. Active transport of Na+and Clacross the canine tracheal epithelium in vitro. Am Rev Respir Dis. 1975;112(6):811-815.
 
Golden JA, Nadel JA, Boushey HA. Bronchial hyperirritability in healthy subjects after exposure to ozone. Am Rev Respir Dis. 1978;118(2):287-294.
 
Caughey GH, Viro NF, Ramachandran J, Lazarus SC, Borson DB, Nadel JA. Dog mastocytoma tryptase: affinity purification, characterization, and amino-terminal sequence. Arch Biochem Biophys. 1987;258(2):555-563.
 
Sigal E, Grunberger D, Craik CS, Caughey GH, Nadel JA. Arachidonate 15-lipoxygenase (omega-6 lipoxygenase) from human leukocytes. Purification and structural homology to other mammalian lipoxygenases. J Biol Chem. 1988;263(11):5328-5332.
 
Sommerhoff CP, Caughey GH, Finkbeiner WE, Lazarus SC, Basbaum CB, Nadel JA. Mast cell chymase. A potent secretagogue for airway gland serous cells. J Immunol. 1989;142(7):2450-2456.
 
Takeyama K, Dabbagh K, Lee H-M, et al. Epidermal growth factor system regulates mucin production in airways. Proc Natl Acad Sci U S A. 1999;96(6):3081-3086.
 
Takeyama K, Dabbagh K, Jeong Shim J, Dao-Pick T, Ueki IF, Nadel JA. Oxidative stress causes mucin synthesis via transactivation of epidermal growth factor receptor: role of neutrophils. J Immunol. 2000;164(3):1546-1552.
 
Shao MXG, Ueki IF, Nadel JA. Tumor necrosis factor alpha-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci U S A. 2003;100(20):11618-11623.
 
Nadel JA. Twenty-five years of airway research: personal thoughts. Proc Am Thorac Soc. 2010;7(6):338-342.
 
Kim S, Lewis C, Nadel JA. Epidermal growth factor receptor reactivation induced by E-prostanoid-3 receptor- and tumor necrosis factor-alpha-converting enzyme-dependent feedback exaggerates interleukin-8 production in airway cancer (NCI-H292) cells. Exp Cell Res. 2011;317(18):2650-2660.
 
Kim S, Beyer BA, Lewis C, Nadel JA. Normal CFTR inhibits epidermal growth factor receptor-dependent pro-inflammatory chemokine production in human airway epithelial cells. PLoS One. 2013;8(8):e72981.
 
Koff JL, Min-Oo G, Ueki I, Kalinowski A, Ballon-Landa E, Lanier L, Nadel JA. Respiratory virus-induced EGFR activation suppresses IRF-1-dependent interferon-λ and antiviral defense in airway epithelium. J Exp Med. 2013;210(10):1929-1936.
 
Gelb AF, Yamamoto A, Mauad T, Kollin J, Schein MJ, Nadel JA. Unsuspected mild emphysema in nonsmoking patients with chronic asthma with persistent airway obstruction. J Allergy Clin Immunol. 2014;133(1):263-265.
 

Tables

Giants in Chest Medicine: Jay A. Nadel, MD

Running Time: 19:28

Suggested Readings

Nadel JA, Comroe JH Jr. Acute effects of inhalation of cigarette smoke on airway conductance. J Appl Physiol. 1961;16:713-716.
 
Nadel JA, Salem H, Tamplin B, Tokiwa Y. Mechanism of bronchoconstriction during inhalation of sulfur dioxide. J Appl Physiol. 1965;20:164-167.
 
Gold WM, Kaufman HS, Nadel JA. Elastic recoil of the lungs in chronic asthmatic patients before and after therapy. J Appl Physiol. 1967;23(4):433-438.
 
Nadel JA, Gold WM, Burgess JH. Early diagnosis of chronic pulmonary vascular obstruction. Value of pulmonary function tests. Am J Med. 1968;44(1):16-25.
 
Goldsmith JR, Nadel JA. Experimental exposure of human subjects to ozone. J Air Pollut Control Assoc. 1969;19(5):329-330.
 
Nadel JA, Wolfe WG, Graf PD, et al. Powdered tantalum. N Engl J Med. 1970;283(6):281-286.
 
Nadel JA, Cabezas GA, Austin JHM. In vivo roentgenographic examination of parasympathetic innervation of small airways. Use of powdered tantalum and a fine focal spot x-ray tube. Invest Radiol. 1971;6(1):9-17.
 
Gelb AF, Gold WM, Wright RR, Bruch HR, Nadel JA. Physiologic diagnosis of subclinical emphysema. Am Rev Respir Dis. 1973;107(1):50-63.
 
Olver RE, Davis B, Marin MG, Nadel JA. Active transport of Na+and Clacross the canine tracheal epithelium in vitro. Am Rev Respir Dis. 1975;112(6):811-815.
 
Golden JA, Nadel JA, Boushey HA. Bronchial hyperirritability in healthy subjects after exposure to ozone. Am Rev Respir Dis. 1978;118(2):287-294.
 
Caughey GH, Viro NF, Ramachandran J, Lazarus SC, Borson DB, Nadel JA. Dog mastocytoma tryptase: affinity purification, characterization, and amino-terminal sequence. Arch Biochem Biophys. 1987;258(2):555-563.
 
Sigal E, Grunberger D, Craik CS, Caughey GH, Nadel JA. Arachidonate 15-lipoxygenase (omega-6 lipoxygenase) from human leukocytes. Purification and structural homology to other mammalian lipoxygenases. J Biol Chem. 1988;263(11):5328-5332.
 
Sommerhoff CP, Caughey GH, Finkbeiner WE, Lazarus SC, Basbaum CB, Nadel JA. Mast cell chymase. A potent secretagogue for airway gland serous cells. J Immunol. 1989;142(7):2450-2456.
 
Takeyama K, Dabbagh K, Lee H-M, et al. Epidermal growth factor system regulates mucin production in airways. Proc Natl Acad Sci U S A. 1999;96(6):3081-3086.
 
Takeyama K, Dabbagh K, Jeong Shim J, Dao-Pick T, Ueki IF, Nadel JA. Oxidative stress causes mucin synthesis via transactivation of epidermal growth factor receptor: role of neutrophils. J Immunol. 2000;164(3):1546-1552.
 
Shao MXG, Ueki IF, Nadel JA. Tumor necrosis factor alpha-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci U S A. 2003;100(20):11618-11623.
 
Nadel JA. Twenty-five years of airway research: personal thoughts. Proc Am Thorac Soc. 2010;7(6):338-342.
 
Kim S, Lewis C, Nadel JA. Epidermal growth factor receptor reactivation induced by E-prostanoid-3 receptor- and tumor necrosis factor-alpha-converting enzyme-dependent feedback exaggerates interleukin-8 production in airway cancer (NCI-H292) cells. Exp Cell Res. 2011;317(18):2650-2660.
 
Kim S, Beyer BA, Lewis C, Nadel JA. Normal CFTR inhibits epidermal growth factor receptor-dependent pro-inflammatory chemokine production in human airway epithelial cells. PLoS One. 2013;8(8):e72981.
 
Koff JL, Min-Oo G, Ueki I, Kalinowski A, Ballon-Landa E, Lanier L, Nadel JA. Respiratory virus-induced EGFR activation suppresses IRF-1-dependent interferon-λ and antiviral defense in airway epithelium. J Exp Med. 2013;210(10):1929-1936.
 
Gelb AF, Yamamoto A, Mauad T, Kollin J, Schein MJ, Nadel JA. Unsuspected mild emphysema in nonsmoking patients with chronic asthma with persistent airway obstruction. J Allergy Clin Immunol. 2014;133(1):263-265.
 
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