Research Centers

1. General Clinical Research Center

The University of Iowa's NIH-sponsored General Clinical Research Center (GCRC) is an outstanding resource for members of this Gene Therapy Core Center conducting gene therapy trials. The GCRC's specialized clinical and laboratory facilities provide a physical and intellectual environment in which clinical investigation can proceed with maximum regard for patient welfare and safety. Funded continuously for 34 years, the GCRC is a discrete unit with dedicated research nurses and dietitians, biostatistical support, and a computer facility, complementing other clinical research programs. At a weekly conference, GCRC investigators present new protocols or review established studies. In addition, biostatistics, new research methodologies, human subjects issues, and ethical considerations are presented. Conferences are attended by investigators, trainees at various levels, nursing staff, and a biostatistician.

2. Cystic Fibrosis Clinical Center

The University of Iowa Cystic Fibrosis Clinical Center, directed by Dr. Michael Weinberger, is a comprehensive, combined adult and pediatric care center with a team of caregivers who provide state-of-the art medical care. The Center is staffed by pediatric and internal medicine pulmonary physicians specializing in cystic fibrosis. The cystic fibrosis team also includes nurse practitioners, nurses, dietitians, respiratory therapists, social workers and clinical pharmacists. Patients of all ages are seen in a common outpatient clinic, located in the Carver Pavilion. For inpatient care, cystic fibrosis patients are admitted to the Cystic Fibrosis wing of the Pediatric Pulmonary Unit or to the Internal Medicine pulmonary ward. In all cases, the attending physician is a member of the Cystic Fibrosis Center.

The Iowa Cystic Fibrosis Clinical Center has a close collaborative relationship with the Cystic Fibrosis Research Center, directed by Dr. Michael Welsh, to pursue clinical and basic science research into the genetics, pathogenesis, and treatment of cystic fibrosis. This is a major focus of the Center, which is facilitated by the comprehensive, combined adult and pediatric care team including physicians involved in both clinical and basic investigation. Center staff physicians and clinical investigators that are also members of the Center for Gene Therapy include Dr. Paul McCray, Dr. Jeff Smith, Dr. Richard Ahrens, Dr. Michael Welsh, and Dr. Joseph Zabner.

CF Related Clinical Trials (in last 5 years):

CFF Gene Therapy Center Pilot and Feasibility Study 3: Physiologic Imaging of Lung: Cystic Fibrosis
PI: Michael Welsh, M.D.
Funding Source: Cystic Fibrosis Foundation
Dates Active: 11/94 - 1/96
Publication:
Evaluation of in vivo total and regional air content and distribution in primate lungs with high-resolution CT. Acad. Radiol. 10:674-9, 1997

Cystic Fibrosis Gene Therapy: In Vivo Safety and Efficacy in Nasal Epithelium
PI: Michael J. Welsh, M.D.
Funding Source: NIH PPG; Howard Hughes Medical Institute
Dates Active: 9/30/92 - 9/95
Publications:
-Adenovirus-Mediated Gene Transfer Transiently Corrects the Chloride Transport Defect in Nasal Epithelia of Patients with Cystic Fibrosis. Cell, 75:207-16, 1993.
-Cystic Fibrosis Gene Therapy Using an Adenovirus Vector: In Vivo Safety and Efficacy in Nasal Epithelium. Human Gene Therapy, 5:209-19, 1994

Adenovirus-Mediated Gene Transfer For Cystic Fibrosis: Safety Of Dose and Repeat Administration in the Nasal Epithelium
PI: Michael J. Welsh, M.D.
Funding Source: NIH
Dates Active: 4/94 - 8/96
Publications:
-Adenovirus-Mediated Gene Transfer for Cystic Fibrosis: Part A. Safety of Dose and Repeat Administration in the Nasal Epithelium. Part B. Clinical Efficacy in the maxillary Sinus. Human Gene Therapy, 6:205-18,1995
-Repeat Administration of an Adenovirus Vector Encoding CFTR to the Nasal Epithelium of Patients with Cystic Fibrosis. J. Clinical Invest. 97:1504-1511,1996.

Measurement of Nasal Electric Potential Difference in Normal and Cystic Fibrosis Patients
PI: Michael J. Welsh, M.D.
Funding Source: Cystic Fibrosis Foundation
Dates Active: 8/94 - present
Publication:
Normal Sweat Chloride Values Do Not Exclude the Diagnosis of Cystic Fibrosis. Amer. Rev. Respir. Med., 151:899-903, 1995

Cationic Lipid Mediated Gene Transfer to Nasal Airway Epithelia of Cystic Fibrosis Patients.
PI: Michael J. Welsh, M.D.
Funding Source: NIH PPG, HHMI and CFF
Dates Active: 1/96 - present
Publication:
Comparison of DNA/Lipid Complexes and DNA Alone for Gene Transfer to Cystic Fibrosis Airway Epithelia In Vivo. J. Clinical Invest. 100: 1529-1537, 1997.

Evaluation of Nasal Airway Fluid for Bactericidal Activity
PI: Joseph Zabner, M.D.
Funding Source: None
Dates Active: 10/96 - present
Publication:
Cystic Fibrosis Airway Epithelia Fail to Kill Bacteria Because of Abnormal Airway Surface Fluid. Cell, 85:229-236, 1996.

The Airway Epithelia Na Channels are Regulated by Aldosterone.
PI:. Joseph Zabner, M.D..
Funding Source: None
Dates Active: 1/96 - present
Publication: The Airway Epithelia Na Channels are Regulated by Aldosterone. In preparation for publication

The Effect of Nebulized Sterile Normal Saline vs. Nebulized Mannitol on the Chloride Concentration in Nasal Epithelia of Normal and Cystic Fibrosis People
PI: Joseph Zabner, M.D.
Funding Source: NIH
Dates Active: 7/96 -present
Sinusitis in Cystic Fibrosis: A Model for Gene Therapy
PI: Joseph Zabner, M.D.
Funding Source: CFF
Dates Active: 10/94 - 8/96
Publication: Sinusitis in Cystic Fibrosis: A Model for Gene Therapy. Submitted 12/5/97 for publication to American Journal of Rhinology

Collection of Fluid From the Nose of Normal and Cystic Fibrosis Patients
PI: Jeffrey J. Smith, M.D.
Funding Source: CFF
Dates Active: 8/95 - Present
Publication:
Cystic Fibrosis Airway Epithelia Fail to Kill Bacteria Because of Abnormal Airway Surface Fluid. Cell, 85:229-236, 1996.

The Cystic Fibrosis Research Center

The University of Iowa's outstanding Cystic Fibrosis Research Center is directed by Dr. Michael Welsh. Other center members include Drs. Joseph Zabner, John Engelhardt, Paul McCray, Peter Greenberg, Jeff Smith, Beverly Davidson and Richard Ahrens. The program is supported by a Cystic Fibrosis Foundation Research Development Program award, an NHLBI Specialized Center for Research on Cystic Fibrosis, and an NHLBI Program Project Grant on Gene Therapy for Cystic Fibrosis Lung Disease. This center supports cores that enhance both the clinical and CF research environment, as well as a seminar series, weekly conferences, and a yearly retreat. Many of the investigators in the Cystic Fibrosis Research Center also care for patients in the Clinical Center. Thus, there is a strong desire to improve the lives of people who have CF. An example of the center's approach to this are the gene transfer studies in humans. One of the major goals of the CF Research Center is to develop gene transfer as a treatment for the disease. The Center has already completed and published three separate studies in humans, more than any other center in the country. All the gene therapy studies have been collaborative efforts between the CF Clinical and CF Research Centers. Advances in the development of new approaches to gene transfer are readily transferred into the clinic for patients.

The Helen C. Levitt Center for Viral Pathogenesis and Disease

The Helen C. Levitt Center for Viral Pathogenesis and Disease was created by a $1 million private bequest to the University of Iowa in March, 1997. The endowment is used to establish a Center to support, in perpetuity, interdisciplinary activities directed to understanding the role of viruses in human disease, revealing mechanisms of viral pathogenesis, developing new approaches to viral disease prevention, diagnosis, and treatment, and improving professional and public understanding of the nature and impact of viral diseases. The Director of the Center is Dr. Stanley Naides, a member of the Center for Gene Therapy. His interests are in the development of new parvoviral vectors for gene delivery. The Center's endowment establishs a dedicated laboratory in the new College of Medicine Biomedical Education and Research Building being built on the University of Iowa medical campus. The fund also supports an outside speakers series, research and education development projects, post-doctoral fellow stipends, and an annual scientific retreat. As the endowment grows, these initial efforts can be expanded and new activities initiated.

The Center for Macular Degeneration

The Center for Macular Degeneration, housed in the new Pomerantz Family Pavilion, is a world-recognized leader in the diagnosis, treatment, and research of macular degeneration. The molecular biology unit of the Center is partially supported by the Carver endowment for Molecular Opthalmology. For the past ten years, Dr. Edwin Stone and Dr. Val Sheffield, both members of the Center, have been actively studying macular degeneration at the cellular and molecular levels. They have identified the locations of genes cause three types of hereditary macular degeneration and have discovered over 100 specific macular-disease-causing mutations. Dr. Beverly Davidson, Director of the Gene Therapy Unit of the Center for Macular Degeneration, has begun to develop methods for delivering functional genes to the retina. In initial experiments "reporter" genes have successfully been delivered to many cell types in the eye with subretinal or intravitreal injections of recombinant adenovirus vectors. The utility of this approach to delivering genes to the eye was also demonstrated in an animal model of retinal degeneration cause by a deficiency in b-glucoronidase. This proof-of-principal experiment is leading to new initiatives in further vector development for gene delivery to the eye.

The Cardiovascular Center

A Cardiovascular Center was established in 1975 by the Dean of the College of Medicine, under the direction of Dr. Francois Abboud, to: 1) coordinate the cardiovascular programs of the College into a more cohesive unit to utilize our cardiovascular resources optimally: 2) intensify, expand and integrate basic and clinical research programs in areas related to cardiovascular research; and 3) evaluate the role of new measures for prevention, diagnosis and treatment of cardiovascular disease. Space totaling 18,000 square feet was constructed at a cost of approximately 2.3 million dollars for the Center and occupied in 1982. The uniquely attractive feature of the Cardiovascular Center programs at Iowa is the close working relationship and cooperation between members of the basic science departments and the members of the clinical departments, particularly the Departments of Medicine, Neurology, Pediatrics and Surgery. Another important element in the success of this Cardiovascular Center has been the availability of a critical mass of basic scientists and clinical investigators who have full-time faculty appointments with tenure at this university. This represents a major commitment of university and state resources to cardiovascular programs, which has been a significant element in its stability and success. The major interdisciplinary programs currently funded within the Cardiovascular Center form the core of research and training programs utilized by postdoctoral trainees in cardiovascular diseases. In addition, an Institutional Cardiovascular Training Grant and an Institutional Pediatric Cardiology Training Grant provide postdoctoral fellowships. Research grants and programs administrated through the Cardiovascular Center include:

PPG on Integrative functions in neurovascular control.
NIH PPG on Cerebral Blood Vessels
NIH PPG on Fatty Acids, Lipoproteins and Lipid Oxidation
SCOR in Molecular Genetics of Hypertension
SCOR in Congenital Heart Disease
SCOR in Occupational and Immunologic Lung Disease
SCOR in Cystic Fibrosis
Cystic Fibrosis Foundation Research and Development Program
PPG on Gene Therapy for Cystic Fibrosis Lung Disease
Cystic Fibrosis Foundation Gene Therapy Center
Training Center in Lipid Disorders
Biostatistics Core Facility