Joseph Zabner, MD, PhD

Associate Director for Translational Science Pilot Program

Director, Division of Pulmonary, Critical Care and Occupational Medicine

Professor, Internal Medicine - Pulmonary, Critical Care and Occupational Medicine

Personal Statement

Dr. Zabner has a long-standing record both in the conduct of clinical/translational research projects and in the translation of basic research into innovative high-risk/high-reward clinical projects.

He is the Vice Chair of Internal Medicine for Translational Research and the Chief of Pulmonary, Critical Care and Occupational Medicine. He has served as Associate Director and Member of the Cystic Fibrosis Research and Development Program and the Gene Therapy Center at The University of Iowa. As Professor of Medicine, Pulmonary and Critical Care, Dr. Zabner leads successful, translational, as well as basic research programs in cystic fibrosis, ventilator-associated pneumonia, and bacterial pathogenesis.

He was a pioneer in gene therapy for cystic fibrosis and led the first gene therapy trial using recombinant adenoviruses. The NIH has funded Dr. Zabner since 1995. Dr. Zabner has published clinical research in high-profile journals and is the holder of several patents in biomedical research. He is frequently invited to present his studies at national and international conferences, and he served as the Chair of the Respiratory Track Gene Therapy Scientific Committee, and has served as a Reviewer for the Lung Cell and Molecular Immunology Study Section.

Education

  • Medical Doctor - Universidad Central de Venezuela, 1987
  • Subintern - Brigham and Women’s Hospital, Harvard, 1988
  • Intern - Presbyterian Hospital, Dallas, 1989
  • Resident - Parkland Hospital, Dallas, 1991
  • Research Fellow - University of Iowa Hospitals and Clinics, 1995

Positions

  • Intern, Internal Medicine, Presbyterian Hospital, Dallas, Texas (1988 - 1989)
  • Resident, Internal Medicine, Parkland Hospital, Dallas, Texas (1989 - 1991)
  • Fellow, Pulmonary Disease, University of Iowa Hospitals and Clinics, Iowa City, IA (1991 - 1994)
  • Assistant Professor, University of Iowa Hospitals and Clinics, Iowa City, IA (1994 - 2000)
  • Associate Professor, University of Iowa Hospitals and Clinics, Iowa City, IA (2000 - 2004)
  • Professor, University of Iowa Hospitals and Clinics, Iowa City, IA (2004 - Present)
  • Key Function Director of ICTS, University of Iowa Hospitals and Clinics, Iowa City, IA (2006 - Present)
  • Interim Director, Division of Pulmonary, Critical Care & Occupational Medicine, University of    Iowa Hospitals and Clinics, Iowa City, IA (2008 - 2010)
  • Director, Division of Pulmonary, Critical Care & Occupational Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA (2010 - Present)  

Honors

  • Parker B. Francis Fellowship Award (1993)
  • American Rhinologic Society, Cottle Award (1998)
  • Central Society for Clinical Research, Outstanding Investigator Award (2001)
  • American Society of Clinical Investigation (2006)
  • American Association of Physicians (2012)
  • Sterba Professor Award, Internal Medicine (2012)
  • Innovator Award (2013)
  • Mentor Teacher of the Year Award (2015)
  • American Clinical and Climatological Association (2015)

Contribution to Science

The focus of my research is on the antibacterial innate immunity of the airway epithelia, in particular how does the lack of a chloride channel ‘CFTR’ results in pulmonary lung infections.  I have divided the research in my laboratory into four main areas.

First, to investigate the antimicrobial properties of the airway surface liquid and how they affect bacterial colonization in cystic fibrosis. My laboratory investigates this question using primary cultures of human airway epithelia at the air liquid interface, animal models including mice and pigs with deletion of the CFTR gene, and humans with cystic fibrosis. We are currently studying the effect pH on airway innate immunity.

  • Pezzulo AA, Tang XX, Hoegger MJ, Abou Alaiwa MH, Ramachandran S, Moninger TO, Karp PH, Wohlford-Lenane CL, Haagsman HP, van Eijk M, Banfi B, Horswill AR, Stoltz DA, McCray PB Jr, Welsh MJ, and Zabner J.  Reduced Airway Surface pH Impairs Bacterial Killing in the Porcine Cystic Fibrosis Lung.  Nature, 2012 Jul 4:487(1405):109-13.   PMCID:  PMC3390761
  • Abou Alaiwa MH, Beer AM, Pezzulo AA, Launspach JL, Horan RA, Stoltz DA, Starner TD, Welsh MJ, Zabner J. Neonates with cystic fibrosis have a reduced nasal liquid pH; a small pilot study. J Cyst Fibros. 2014 Jul;13(4):373-7.doi:10.1016/j.jcf.2013.12.006. Epub 2014 Jan 11.PMCID: PMC4060428
  • Hoegger MJ, Fischer AJ, McMenimen JD, Ostedgaard LS, Tucker AJ, Awadalla MA, Moninger TO, Michalski AS, Hoffman EA, Zabner J, Stoltz DA, Welsh MJ.  Science. 2014 Aug15;345(6198):818-22. doi: 10.1126/science.1255825. PMCID: PMC4346163

Second, I investigate the development of vectors for gene therapy in cystic fibrosis. I initially worked on non viral vectors, and described the molecular mechanism for transfection. I also tested a non-viral vector and an adenovirus vector in human experiments to investigate the proof of principle for gene transfer to the airways of patients with CF. Currently, I have been using ‘directed evolution’ to select adeno-associated viruses that efficiently target the airway epithelia of humans and pigs. The porcine model of Cystic Fibrosis will allow us to ask the question if ‘gene transfer’ can result in ‘gene therapy’.

Third, my laboratory also investigates how the receptor for adenovirus regulates epithelial functions as well as pathogenesis of adenovirus airway infection.

  • Walters RW, Grunst T, Bergelson JM, Finberg RW, Welsh MJ, Zabner J:  Basolateral Localization of Fiber Receptors Limits Adenovirus Infection of Airway Epithelia.  J. Biol. Chem., 274(15):10219-10226, 1999.
  • Excoffon KJ, Gansemer ND, Mobily ME, Karp PH, Parekh KR, Zabner J. Isoform-specific regulation and localization of the coxsackie and adenovirus receptor in human airway epithelia. PLoS One. 5(3):e9909, 2010. PMCID: PMC2845650

Finally, I have been investigating the effect of an endogenous lactonase ‘paraoxonase’ that can degrade quorum-sensing molecules used by Pseudomonas Aeruginosa. This family of proteins is ubiquitously expressed in the airways and may represent a novel form of innate immunity against quorum-sensing bacteria.

  • Stoltz DA, Ozer EA, Taft PJ, Barry M, Liu L, Kiss PJ, Moninger TO, Parske MR, Zabner J. Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1. J Clin Invest. 118(9):3123-3131, 2008. PMCID: PMC2515384
  • Stoltz DA, Ozer EA, Recker TJ, Estin M, Yang X, Shih DM, Lusis AJ, Zabner J. A common mutation in paraoxonase-2 results in impaired lactonase activity. J Biol Chem. 284(51):35564-71, 2009. PCMID: 2790986.

Publications

Ongoing Research Support

PPG- Zabner (PI)

08/01/2013-06/30/2018      

NIH: HL091842                                                                                                                                                                            

Airway Physiology and Pathophysiology in a Porcine CF Model- Administrative Core

PPG- Zabner (PI)

08/01/2013-06/30/2018    

NIH: HL091842                                                                                                                                                                                  

Airway Physiology and Pathophysiology in a Porcine CF Model- Project 3

PPG- Zabner (PI)

08/01/2013-06/30/2018    

NIH:  HL091842                                                                                                                                                                                 

Airway Physiology and Pathophysiology in a Porcine CF Model- InVitro Models & Cell Culture Core

CenterPRO- Zabner (PI)

04/01/2015-09/30/2020   

NIH:  DK54759-16                                                                                                                                                                                               

Center for Gene Therapy of Cystic Fibrosis & Other Genetic Diseases

PPG- Zabner (PI)

8/01/2015-5/31/2020

NIH: PPGPRO HL51670

Gene Therapy for Cystic Fibrosis Lung Disease: Cell Culture Core

PPG- Zabner (PI)

8/01/2015-5/31/2020

NIH: PPGPRO HL51670

Gene Therapy for Cystic Fibrosis Lung Disease: Project 1

R01- Zabner (PI)

04/01/2017-03/31/2022

NIH: HL136813-01

Airway Alkalinization and Repurposing Tromethamine as a Therapeutic Approach in Cystic Fibrosis

Completed Research Support

CenterPRO DK54759-14 Engelhardt (PI)

04/01/09-03/31/14

NIH

Cells and Tissue Culture:  Center for gene therapy of cystic fibrosis and other genetic diseases.

NIH PPGPRO HL51670-19 McCray (PI)

08/01/09-07/31/14

Gene Therapy for Cystic Fibrosis Lung Disease:  In Vitro Models & Cell Culture Core

Role: Director of In Vitro Models & Cell Culture Core

NIH PPGPRO HL51670-19 McCray (PI)

08/01/09-07/31/14

Gene Therapy for Cystic Fibrosis Lung Disease

Project Leader #1: Directed Evolution of AAV for Gene Therapy in a Pig Model of Cystic Fibrosis

Role: PI of Project 1

RDP- Zabner (PI)

08/01/09-07/31/2015

NIH: PPGPRO HL51670-20                                                                                                                               

Gene Therapy for Cystic Fibrosis Lung Disease: In Vitro Models and Cell Culture Core

Center Pro- Zabner PI

04/01/2009-03/31/2015      

NIH: DK54759-15                                                                                                                                                                              

Cells and Tissue Culture: Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases

PPGPRO- Zabner (PI)

08/01/2009-07/31/2015      

NIH: PPGPRO HL51670-20                                                                                                                               

Gene Therapy for Cystic Fibrosis Lung Disease: Interactions of AAV5 with sialic acid and PDGF receptors

U01-Zabner (PI)

07/01/2010-06/30/2015      

NIH: HL102288-03                                                                                                                                                                             

Iowa Phase II Clinical Trials of Novel Therapies for Lung Diseases

RDP- Zabner (PI)

07/01/2011-06/30/2015      

CFF:  R458-CR11

Iowa Cystic Fibrosis Foundation Research & Development Program- Clinical Research Core

 

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