Gastrointestinal Manifestations of CF: Basic Science Projects

The intent of this request for applications is to solicit and fund projects that will improve our understanding of the biological basis for the development and progression of gastrointestinal manifestations in cystic fibrosis as well as to identify potential novel therapeutic strategies to manage and treat them.

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Cystic fibrosis results from inadequate functional cystic fibrosis transmembrane conductance regulator (CFTR) protein, which may affect both bicarbonate and chloride transport in many different organ systems. Although most commonly described as a lung disease, nearly all people with CF experience at least one gastrointestinal (GI), pancreatic, or hepatic complaint during their lifetime. Studies have shown that the recognition and management of extrapulmonary complications is important for maintaining health in CF — including but not limited to improving growth, nutrition, and pulmonary function — but also has significant impacts on quality of life.  

The landscape of CF has changed significantly over the last decade with the introduction of CFTR modulating drugs that target the basic CFTR defect for nearly 90% of people in the U.S. living with CF. Although modulators have significantly improved health outcomes for many people with CF, we also are starting to realize the changing course of the disease and some of the complications that persist with treatment, as well as new aspects of the disease that people are experiencing for the first time. 

Some of the major GI complications/manifestations experienced by people with CF include: 

  • Distal intestinal obstruction syndrome (DIOS)
  • Motility issues/disorders
  • Gastroesophageal reflux disease (GERD)
  • Exocrine pancreatic insufficiency (EPI)
  • Pancreatitis
  • Hepatobiliary disease
  • GI malignancies

GI manifestations can be complex with some originating as the direct result of the malfunction or deficiency of the CFTR protein while others may be the result of downstream effects of the disease or its treatment. To better understand the biological underpinnings of many of these manifestations, we are soliciting applications for basic science research projects on the topic. Some of the areas of greatest interest include:  

  • Impacts of CFTR function on 
    • Fluid characteristics (e.g., viscosity, ionic concentrations, volume, pH) and flow dynamics
    • Mucus abnormalities, especially in the GI tract 
  • GI inflammation
  • Impact of small intestinal bacterial overgrowth (SIBO)/gut microbiome on GI complications and nutrition*
  • Pancreas/intestine interactions
  • Gut/liver axis 
  • Changes in cellular biology that occur with CFTR dysfunction including:
    • Expression and/or functional impacts on tissue/cell homeostasis and repair 
    • Cell fate determinations/signaling 
  • Genes and pathways contributing to pathophysiology/pathogenesis including:
    • Genetic modifiers and tissues of expression
    • Potential to impact genetic modifier targets
  • CFTR-modulator reversible and non-reversible disease components:
    • Knowledge and gaps regarding CFTR modulator impact on GI, pancreatic, and hepatobiliary disease across the lifespan
    • Impact of early modulator use on restoration of organ level function
    • Relative CFTR modulation across CFTR-expressing tissues that may contribute to the development of GI manifestations
  • Elucidating pathophysiology and/or development of therapy directed at correcting nutritional deficiencies

The Foundation may also consider proposals to develop and validate tools or reagents that could be used to facilitate research into GI, pancreatic, and hepatic complications. Examples may include: 

  • Development of tissue-specific cell models that could be shared with other investigators 
  • Development of validation of CFTR antibodies in immunofluorescence detection in native tissues

Note: Although the focus of research projects should be on CF relevant biology, proposals may also include research into the overlap or commonalities with other diseases. We welcome proposals from individuals with experience in CF but are particularly interested in applications from individuals with expertise in other areas or techniques that can be applied to the above areas of interest.

*Projects proposing high throughput sequencing or ‘omics methodologies to characterize the microbial community will be considered only if they also include detailed plans for use of the data or confirmatory studies to begin to understand mechanisms.

Grant applications submitted through this request for applications (RFA) must focus on basic science research projects. Proposals that include methodologies requiring human subjects or sampling of materials from human subjects will be considered under this mechanism only if the sampling method constitutes minimal patient risk (e.g., venipuncture, nasal brushings) and the sample will be utilized in basic or laboratory research. Projects using previously obtained human samples or samples collected as part of routine clinical care may be allowed; however, this should be specified clearly in the application. All other projects involving human subjects, including interventional studies, will not be reviewed nor funded through this award mechanism. Applicants should instead submit their proposals under the Clinical Research Award or Clinical Pilot and Feasibility Award mechanisms. Please refer to the Policies and Guidelines of each of these programs.

The CF Foundation offers funding of up to $150,000 per year for up to three years. (Indirect costs up to 12% are allowable.)

A second cycle of this RFA will be announced in early 2024. 

Policies and Guidelines

Please review the 2023 Policies and Guidelines for complete submission information.


Applications must be submitted online at by 5 p.m. ET on July 19, 2023.

For More Information

Those who are interested in any funding programs offered by the CF Foundation can get further information or discuss the potential relevance of their studies or research by contacting the Grants & Contracts Management and Administration (GCMA) Office at

Please Direct Inquiries to:
GCMA Office
Cystic Fibrosis Foundation
4550 Montgomery Ave.
Suite 1100 N
Bethesda, MD 20814


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