University of Cincinnati Department of Pediatrics

Bruce C. Trapnell, MD, MS

Title

Assistant Director, Adult Cystic Fibrosis Center; Director, Viral Vector Core Laboratory

Appointment

Professor of Medicine and Pediatrics; Attending Physician; Co-Director, Cincinnati Cystic Fibrosis Therapeutics Development Center; Director, Rare Lung Diseases Clinical Research Foundation; Scientific Director, Alpha-1 Foundation

Email

bruce.trapnell@cchmc.org

Phone

513-636-6361

Fax

513-636-3723

Bio

Bruce Trapnell, MD, an internationally recognized expert in gene therapy, is assistant director of the Adult Cystic Fibrosis Center at the University of Cincinnati. Dr. Trapnell is also the director of the Viral Vector Core laboratory at The Children's Hospital Research Foundation.

Dr. Trapnell joined the staff of Cincinnati Children's Hospital Medical Center in 1997. He came from Maryland, where he was vice president and director of Virology and Pulmonary Studies at Genetic Therapy, Inc., Novartis, and Assistant Professor of Medicine at Georgetown University School of Medicine in Washington, DC. He earned his undergraduate degree in biochemistry at the University of Maryland, a masters in genetics at The George Washington University in Washington, DC, and his medical degree at the University of Maryland. After completing a residency in internal medicine at The Ohio State University hospitals and a fellowship in pulmonary medicine at the National Institutes of Health (NIH), he served as attending physician in the cystic fibrosis clinic at the NIH until coming to Cincinnati.

An internist and adult pulmonologist by training, Dr. Trapnell has worked throughout his career to define the biological mechanisms of inflammatory lung disorders, especially focusing on cystic fibrosis and pulmonary fibrosis. He was involved in the initial efforts to develop human gene therapy for cystic fibrosis lung disease at the NIH and was co-investigator on the human gene therapy clinical trial conducted at Cincinnati Children's Hospital Medical Center. He has published more that 60 articles and 80 abstracts.

Credentials

MS: Genetics, The George Washington University, Washington, DC, 1981.

M.D.: University of Maryland School of Medicine, Baltimore, MD, 1984.

Residency: Internal Medicine, The Ohio State University Hospitals, Columbus, OH, 1987.

Fellowship: Pulmonary Medicine, Warren Grant Magnasun Clinical Center, National Institutes of Health, Bethesda, MD, 1989.

Certification: Diplomate, American Board of Internal Medicine, 1987.

Research

Dr. Bruce Trapnell's laboratory seeks to:

Determine the mechanisms of innate immune lung host defense that mediate inflammation during viral infection of the respiratory tract and that mitigate the effectiveness of in vivo gene transfer to the lung
Determine mechanisms governing alveolar macrophage terminal differentiation and acquisition of functional capacity in the lung that will provide insight into the pathogenesis of lung inflammation in disorders such as cystic fibrosis and pulmonary fibrosis

The role of hematological growth factor GM-CSF and M-CSF in the control of alveolar macrophage recruitment to the lung, differentiation and acquisition of function are being addressed. In vivo adenovirus and retrovirus vector-mediated gene transfer together with transgenic and knockout mouse models are being utilized to study the pathogenesis of virus-induced lung inflammation and develop gene therapy for respiratory diseases.

Publications, Most Recent

Connelly, S.; Andrews, J.L.; Gallo, A.M.; Kayda, D.B.; Qian, J.; Hoyer, L.; Kadan, M.J.; Gorziglia, M.I.; Trapnell, B.C.; McClelland, A.; Kaleko, M.: Sustained phenotypic correction of murine hemophilia A by in vivo gene therapy.Blood, 1998; 91(9): 3273-81.

Czubayko, F.; Downing, S.G.; Hsieh, S.S.; Goldstein, D.J.; Lu, P.Y.; Trapnell, B.C.; Wellstein, A.: Adenovirus-mediated transduction of ribozymes abrogates HER-2/neu and pleiotrophin expression and inhibits tumor cell proliferation.Gene Ther, 1997; 4(9): 943-9.

Harrod, K.S.; Hermiston, T.W.; Trapnell, B.C.; Wold, W.S.; Whitsett, J.A.: Lung-specific expression of adenovirus E3-14.7K in transgenic mice attenuates adenoviral vector-mediated lung inflammation and enhances transgene expression.Hum Gene Ther, 1998; 9(13): 1885-98.

Harrod, K.S.; Trapnell, B.C.; Otake, K.; Korfhagen, T.R.; Whitsett, J.A.:SP-A enhances viral clearance and inhibits inflammation after pulmonary adenoviral infection.Am J Physiol, 1999; 277(3 Pt 1): L580-8.

Iwamoto, H.S.; Trapnell, B.C.; McConnell, C.J.; Daugherty, C.; Whitsett, J.A.: Pulmonary inflammation associated with repeated, prenatal exposure to an E1, E3-deleted adenoviral vector in sheep.Gene Ther, 1999; 6(1): 98-106.

March, K.L.; Woody, M.; Mehdi, K.; Zipes, D.P.; Brantly, M.; Trapnell, B.C.: Efficient in vivo catheter-based pericardial gene transfer mediated by adenoviral vectors.Clin Cardiol, 1999; 22(1 Suppl 1): I23-9

Otake, K.; Ennist, D.L.; Harrod, K.; Trapnell, B.C.: Nonspecific inflammation inhibits adenovirus-mediated pulmonary gene transfer and expression independent of specific acquired immune responses.Hum Gene Ther, 1998; 9(15): 2207-22.

Schwarz, Y.A.; Amin, R.S.; Stark, J.M.; Trapnell, B.C.; Wilmott, R.W.: Interleukin-1 receptor antagonist inhibits interleukin-8 expression in A549 respiratory epithelial cells infected in vitro with a replication- deficient recombinant adenovirus vector. Am J Respir Cell Mol Biol, 1999; 21(3): 388-94.

Zsengeller, Z.K.; Wert, S.E.; Bachurski, C.J.; Kirwin, K.L.; Trapnell, B.C.; Whitsett, J.A.: Recombinant adenoviral vector disrupts surfactant homeostasis in mouse lung.Hum Gene Ther, 1997; 8(11): 1331-44.

Zsengeller, Z.K.; Boivin, G.P.; Sawchuk, S.S.; Trapnell, B.C.; Whitsett, J.A.; Hirsch, R.: Anti-T cell receptor antibody prolongs transgene expression and reduces lung inflammation after adenovirus-mediated gene transfer.Hum Gene Ther, 1997; 8(8): 935-41.

Trapnell, B.C.; Gene Therapy For Cystic Fibrosis Lung Disease. In The Pediatric Lung, Wilmott, R.W., Ed., Birkhauser, Switzerland, 1997.

Uchida K, Nakata K, Trapnell BC, Terakawa T, Hamano E, Mikami A, Matsushita I, Seymour JF, Oh-eda M, Ishige I, Eishi Y, Kitamura T, Yamada Y, Hanaoka K, and N Keicho. High Affinity Autoantibodies Specifically Eliminate Granulocyte-Macrophage Colony-Stimulating Factor Activity In The Lungs Of Patients With Idiopathic Pulmonary Alveolar Proteinosis. (In Press).

Katakura S, Jennings K, Watanabe S, Gao G-P, Wilson JM, Burstein H, Trapnell BC, and Hirsch R. Recombinant Adeno-associated Virus preferentially transduces human, compared to mouse, synovium: implications for therapy of arthritis. (In Press).

Cheng Y-H, Aronow BJ, Hossain S, Trapnell BC, Kong S and Handwerger S. Critical role for transcription factor AP-2 in human trophoblast differentiation. (In press).

Jennings K, Miyamae T, Katakura S, Trapnell BC, Wilson JM, Gao G, Sowders D, and R Hirsch. Proteasome Inhibition Enhances AAV-Mediated Transduction fo Human Synoviocytes In Vitro and In Vivo.

Grants

2001 – 2005 R01 HL69459, NIH-NHLBI; Total direct costs: $1,125,000 Role: Principal Investigator; Effort: 35%
Title: GM-CSF and Alveolar Macrophage Antiviral Lung Host Defense

1999 – 2004 2 P01 HL61646, NIH-NHLBI Total Direct Costs: $1,193,774
Role: Co-Investigator (PI: A. Jobe); Effort: 10%
Title: PPG: Surfactant Homeostasis in Health and Disease, Project 3: Modulation of Lung Innate Defenses by SP-A (PI: J Whitsett)

2001 – 2006 2P50 HL5638706, NIH/NHLBI; Total direct costs: $1,356,697
Role: Co-Investigator (PI: J Whitsett); Effort: 15%
Title: Specialized Center of Research (SCOR) Pathobiology of Lung Development
Project 2: Fibroblast Growth Factors in Lung Morphogenesis (PI: J Shannon

2001 – 2006 R01 AR47322, NIH/NIAMS-NIAID Total direct costs: $1,000,000
Role: Co-Investigator (PI: Ram) Effort: 5%
Title: Peptide Vaccination in Lupus

2002 – 2004 No Number Assigned; Alpha-1 Foundation; Total direct costs: $100,000
Role: Principal Investigator Effort: 5%
Title: Scientific Director of the Alpha-1 Foundation

2002 – 2006 R01 HL071823,NIH/NHLBI Total direct costs: $1,000,000 Role: Principal Investigator; Effort: 20%
Title: Regulation of Phagocytosis by Alveolar Macrophages

2002 – 2007 Cystic Fibrosis TDN Center, CFF Total direct costs $564,166
Role: Co-Principal Investigator; Effort: 10%;
Title: Therapeutics Development Center

2003 Translational Research Initiative Grant, CCHMC Total direct costs $100,000 Role: Co-Investigator (PI: P-Y Berclaz); Effort: 5%
Title: Role of Evi-1 and PU.1 in Inhibition of Myeloid Differentiation in AML

2003 – 2008 1 U54 RR019498-01, NIH-NCRR Total direct costs: $4,498,195 Role: Principal Investigator; Effort: 20%
Title: Rare Lung Disease Clinical Research Network

2004 R13, NIH, NHLBI Total direct costs: $29,000
Role: Principal Investigator; Effort: 0%
Title: Second Annual International Pulmonary Alveolar Proteinosis Research Conference

Special Interests

Cystic fibrosis; inflammatory lung disease; gene therapy. Editing

Dr. Trapnell serves as an ad hoc reviewer for the following journals:

American Journal of Physiology,
Cancer Research,
Journal of Pediatrics,
Journal of Virology,
Gene Therapy,
Human Gene Therapy,
Journal of Biological Chemistry,
Journal of Clinical Investigation,
Lung,
Nature Medicine,
Proceedings of the National Academy of Science and Respiratory Cell and Molecular Biology.

Presentations

Adenovirus Vectors for Human Gene Therapy: Progress and Current Challenges, Boden Conference on Gene Therapy,Thredbo, Australia, 1997.

Regulation of Inflammatory Mechanisms, 38th Congress of the German Society of Pneumology, Freiburg, Germany, 1997.

Gene Therapy, Maryland Academy of Family Physicians, Ocean City, Md., 1997.

Innate Host Defenses and Pulmonary Gene Transfer, University of Florida, Gainsville, Fla., 1998.

Human Gene Therapy: Current Progress, Prospects and Challenges. Presented at Amgen Inc., Thousand Oaks, Calif., 1998.

Evaluation of the Concentration, Quality and Bioactivity of Adenoviral Vectors, The sixth Symposium on Gene Therapy "Towards Gene Therapeutics," Berlin, Germany, 1998.

The Role of Innate Host Defense in Adenovirus-Mediated Pulmonary Gene Transfer, University of Cincinnati College of Medicine, Cincinnati, Ohio, 1998.

Role of the Alveolar Macrophage in Innate Defense of Adenoviral Vector-Mediated Pulmonary Gene Transfer, University of Cincinnati College of Medicine, Cincinnati, Ohio, 1998.

Current Progress, Challenges and Prospects for Gene Therapy, Children's Hospital Medical Center, Cincinnati, Ohio, 1998.

Chaired symposia and workshops:

Workshop: Achieving Persistence with Viral Vectors.The 11th Annual North American Cystic Fibrosis Meeting, Nashville, Tenn., 1997.

Session: Gene Therapy for Alpha 1-Antitrypsin Deficiency. The first Alpha One Foundation Annual Meeting, Haverford College, Pa., 1999.

Session: Novel Approaches For Airway-Specific Gene Therapy, 96th International Conference of the American Thoracic Society, Toronto, Canada.

Professional Organizations

American Association for the Advancement of Science

American College of Physicians

American Federation of Clinical Research

American Society for Gene Therapy

American Thoracic Society