Michael R Knowles, MD

Links Research Biosketch Collaborations Personnel Contact

Dr. Michael R Knowles is a Professor of Pulmonary and Critical Care medicine at UNC. He has over 3 decades of clinical research experience that spans across the disciplines of biology, physiology, and design of clinical trials in both the academic and private sectors. He is currently the head of two large multicenter studies: 1) Genetic Modifiers of Disease phenotype (severity) in cystic fibrosis lung and liver disease, which also includes a recently formed International Consortium doing a whole genome scan; and 2) a Consortium with 8 sites in North America to study rare genetic disorders of mucociliary clearance.

Knowles Figure 1

Schematic drawing of the eukaryotic cilium.

Links

UNC Gene Modifiers Study

UNC PCD Research and Treatment

COPD Foundation

ALPHA-1 Foundation

Genetic Diseases of Mucociliary Clearance Consortium

Rare Clinical Diseases Research Network

PCD Foundation

Cystic Fibrosis Foundation

UK PCD Family Support Group

Research

Genetic Disorders of Mucociliary Clearance. NIH/NHLBI (Knowles).
The major goal of this project is to establish a network of geographically-dispersed clinical research sites that are designed to study rare diseases of the airways. These sites will collaborate in diagnostic, genetic, and a range of other studies in mucociliary clearance, including primary ciliary dyskinesia (PCD). A major focus is the identification of disease-causing genes for PCD.

Genetic Modifiers in CF Lung Disease. NIH/NHLBI (Knowles).
The major goals of this study are to identify associations between non-CFTR genes and the pulmonary phenotype, and test for the association of candidate modifier alleles with severity (or mildness) of pulmonary disease. Identification of genes that modulate the severity of the pulmonary phenotype will improve understanding of the pathophysiology of CF lung disease and identify new targets for therapeutic intervention.

Genetic Modifiers in CF Liver Disease (Knowles and Stonebraker).
This study examines "modifier genes" that may play a role in the development of CF liver disease. Modifier genes are genes, other than the CF gene (CFTR), which may directly or indirectly have an effect on how the body responds to the conditions that develop as the result of the defective CFTR gene. The identification of modifier genes that influence disease severity may ultimately lead to a better understanding of CF liver disease, and may be useful in the development of new treatments.

Pathogenesis of PCD Lung Disease. NIH/NHLBI (Knowles).
The major goals of this project are to define the ciliary physiologic phenotype of PCD, and investigate the molecular, pathogenesis of lung disease associated with defective MCC, including underlying genetic causes of disease.

Molecular Phenotypes for Cystic Fibrosis Lung Disease. NIH/NHLBI (Knowles, Wright, O'Neal).
The major goal of this project is to define a robust molecular phenotype for CF lung disease, which relates to prognosis, and new targets for therapy.

Bronchiectasis Research Registry. COPD Foundation, (Knowles).
This project is to fund creation and maintenance of a database of patient information for bronchiectasis research.

Genetic Modifiers of Cystic Fibrosis: Twins & Siblings. UNC Subcontract: (Knowles).
The goal of this project is to recruit every CF twin pair and sibling set living across the U.S and to gather information about their diagnosis, clinical course, growth and pulmonary disease, to determine the participant’s "phenotype" (clinical picture). The overall goal of the study is to identify modifiers of Cystic Fibrosis severity and develop treatments or preventions.

A wide area of a normal (non-CF) airway epithelial cell culture in profile. Beads in the solution enable the visualization of the flow
caused by the beating cilia. Video courtesy of Dr. Patrick Sears.

Collaborations

Collaborations are essential to the research currently undertaken in the Knowles research lab. These include investigators and patients from both national and international sites. The world-wide CF and PCD communities have come together to aid in the projects below. While we are unable to list all the sites who have contributed, the founding members include the following investigators.

Genetic Modifiers of CF Liver and Lung Disease Research

International CF Modifier Consortium (coordinating members include):

The University of North Carolina at Chapel Hill, Mike Knowles, MD
Case Western Reserve University, Cleveland, OH, Mitch Drumm, PhD
Johns Hopkins University, Baltimore, MD, Garry Cutting, MD
The Hospital for Sick Children, Toronto, Canada, Peter Durie, MD
The Hospital for Sick Children, Toronto, Canada, Simon Ling, MD
Trousseau Hospital, Paris, France, Harriet Corvol, MD

Primary Ciliary Dyskinesia Research

Genetic Disorders of Mucociliary Clearance Consortium (coordinating members include):

The University of North Carolina at Chapel Hill, Mike Knowles, MD
University of Florida, Alexandra Quittner, MD
University of South Florida, Jeff Krischer, PhD
Washington University in St. Louis, Tom Ferkol, MD and Jeff Atkinson, MD
The Children’s Hospital, Denver, Scott Sagel, MD
National Jewish Health, Denver, Chris Czaja, MD
Stanford University, Carlos Milla, MD
Children’s Hospital & Regional Medical Center, Seattle, Margaret Rosenfeld, MD
The Hospital for Sick Children, Toronto, Canada, Sharon Dell, MD
NIH NIAID, Ken Olivier, MD
St. Michael's Hospital, David Hall, M.D., and Raymond Kim, MD. Denver, Scott Sagel, MD

National

Cecilia Lo, PhD, University of Pittsburg, and Linda Leatherbury, MD, Laboratory of Developmental Biology, NHLBI, Bethesda, MD

International

Heymut Omran, MD, Munster, Germany
Jane Lucas, MD, South Hampton U. Hospital NHS Trust, UK
Lucy Morgan, University of Sydney, Australia
Estelle Escudier, MD, Unite Inserm, Faculte de Medecine de Creteil, Cedex, France
Serge Amselem, MD, Unite Inserm, Faculte de Medecine de Creteil, Cedex, France

Biographical Sketch

Michael R Knowles, PhD, Professor of Medicine

Education

(1967) University of North Carolina at Chapel Hill, NC, A.B., Chemistry.

(1971) University of North Carolina at Chapel Hill, NC, M.D., Medicine.

(1975) Duke University, Durham, NC, Resident, Medicine.

(1980) University of North Carolina at Chapel Hill, NC, Fellow, Medicine.

Professional Experience

1975-1978 Chief, Internal Medicine; USAF, Malcolm Grow Medical Ctr., Andrews AFB, Washington, DC.

1980-1982 Instructor, Department of Medicine, The University of North Carolina, Chapel Hill, NC.

1982-1987 Assistant Professor, Medicine, Dept. of Medicine, The U. of North Carolina, Chapel Hill, NC.

1982- Director/Co-director, UNC Adult CF Clinical Center, The U. of North Carolina, Chapel Hill, NC.

1987-1994 Associate Professor, Medicine, Dept. of Medicine, The U. of North Carolina, Chapel Hill, NC.

1994- Professor of Medicine, Dept. of Medicine, The University of North Carolina, Chapel Hill, NC.

Honors

1963-1967 Morehead Scholar, The University of North Carolina, Chapel Hill, NC.

1977-1978 Instructor, Medicine, Uniformed Services University of Health Sciences, Bethesda, MD.

1983-1987 Jefferson Pilot Fellowship in Academic Medicine, The U. of North Carolina at Chapel Hill.

1988-1989 Research Sabbatical: Medical Research Council, Cambridge, England.

1988-1989 Visiting Clinical Scholar, Heart-Lung Transplantation Unit, Papworth, England.

2008 Paul A. Di Sant'Agnese Award, CFF 22nd Annual North American CF Conference.

2011 Doris F. Tulcin Cystic Fibrosis Award.

Awards

Paul di Sant’Agnese Award (2008).

Cystic Fibrosis Foundation (2008).

Doris F. Tulcin Cystic Fibrosis Award (2011).

Publications

Please see PubMed feed in the right hand column for links to current publications.

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Personnel

Beth Godwin, BA, Business Officer

Xueliang Guo, PhD, Research Associate

Kathy Hohneker, RN, BSN, Adult CF Center Clinical Nurse

Veronica Moore, MA, Social Clinical Research Assistant

Rhonda G. Pace, BS, Research Specialist

Michael Patrone, BS, Social Clinical Research Assistant

Jaclyn Stonebraker, PhD, Research Associate

Kathy Thurlow, MS, Social Clinical Research Assistant

Whitney Wolf, BS, Research Specialist

Maimoona Zariwala, PhD, Research Associate Professor of Pathology

Contact Information

7019 Thurston-Bowles Bldg.
The University of North Carolina at Chapel Hill
Campus Box #7248
Chapel Hill, NC 27599
Phone: (919) 966-6780
Email: knowles@med.unc.edu

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KEY WORDS: cystic fibrosis, genetic modifiers, primary ciliary dyskinesia, pseudohypoaldosteronism