SUMMARY
The research of Fouad T. Chebib, M.D., spans the molecular, translational and clinical aspects of autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary kidney disease.
Dr. Chebib's research is centered on identifying disease mechanisms and translating those insights into effective therapies to prevent or delay kidney failure in ADPKD. His laboratory has discovered previously unrecognized pathways in renal water handling and cystogenesis and is actively engaged in developing small-molecule therapeutics targeting these novel mechanisms. His multidisciplinary approach combines cell and animal models, high-throughput screening, and patient-derived datasets to drive therapeutic innovation.
A national leader in ADPKD clinical care and research, Dr. Chebib co-authored the U.S. consensus guidelines on the use of tolvaptan and led the creation of one of the first dedicated tolvaptan clinics in the country. He continues to design and lead investigator-initiated clinical trials and translational studies that bridge bench discoveries with bedside care.
Focus areas
- Novel pathways of water regulation in ADPKD. Dr. Chebib explores alternative mechanisms regulating renal water reabsorption that bypass vasopressin signaling. These investigations have led to the identification of novel mechanisms and have catalyzed the development of first-in-class therapeutic strategies. His lab is evaluating novel small molecules with the goal of moving them toward clinical testing.
- Role of calcium and cAMP signaling in cystogenesis. Disruption of intracellular calcium is believed to underlie cAMP upregulation and the proliferative phenotype of cystic epithelia in ADPKD. Dr. Chebib investigates how polycystins regulate calcium flux and how aberrant calcium-cAMP signaling contributes to cyst growth. This work includes studies on ion channels such as TRPV2 and the role of purinergic signaling in cyst pathophysiology.
- Mechanotransduction and PKD progression. ADPKD is marked by structural deformation of the renal tubule and impaired sensing of mechanical forces. Dr. Chebib studies the role of mechanosensitive ion channels such as PIEZO1 and their interaction with the polycystin complex to understand how mechanical signals regulate cyst initiation and expansion. His lab recently demonstrated that pharmacologic activation of PIEZO1 suppresses cystogenesis in preclinical models.
- Genotype-phenotype characterization in ADPKD. Despite being a monogenic disorder, ADPKD displays wide variability in disease expression. Dr. Chebib leverages Mayo Clinic's large ADPKD registry to study the effect of rare and common variants on renal and extrarenal manifestations, including hepatic cysts and cardiovascular abnormalities. His team also is leading efforts to characterize the clinical trajectory of atypical genotypes such as ADPKD-IFT140.
- Radiogenomics and AI-guided risk stratification. Dr. Chebib works closely with radiologists and data scientists to develop advanced imaging biomarkers and automated cyst segmentation tools using artificial intelligence. These efforts aim to refine prediction models of disease progression and guide personalized therapy in ADPKD. His lab integrates imaging, genetic and molecular data to create actionable risk profiles for clinical and research use.
- Implementation of therapies and clinical trial innovation. In addition to his translational research, Dr. Chebib is committed to ensuring that promising therapies reach patients efficiently. He designed and leads SereNDIpity-pb1, an investigator-initiated trial exploring a repurposed medication to mitigate tolvaptan-induced polyuria. His work bridges discovery and implementation, ensuring that scientific advances translate into improved clinical care.
Significance to patient care
Dr. Chebib is working to stop kidney failure in people with ADPKD before it starts. He focuses his research on finding the disease early, understanding each person's risk, and developing treatments that are both safe and effective. His work combines patient care, new technology and research to bring new hope to individuals affected by polycystic kidney disease.
Professional highlights
- Mayo Clinic:
- Director, Discovery and Translational PKD Research Laboratory, 2022-present.
- Director, Polycystic Kidney Disease (PKD) Center of Excellence, 2022-present.
- Catalyst Award, Florida campus, 2023.
- New Investigator of the Year Award, Florida campus, 2023.
- Team Science Award as part of the Mayo Clinic Robert and Billie Kelley Pirnie Translational Polycystic Kidney Disease (PKD) Center team, Rochester campus, 2020.
- Co-chair, PKD Foundation Centers of Excellence Advisory Committee, 2021.
- Co-author, U.S. consensus guidelines on the use of tolvaptan in ADPKD, Journal of the American Society of Nephrology, 2018.