SUMMARY
Summary
Fouad T. Chebib, M.D., is a nephrologist whose research spans the molecular, translational and clinical aspects of autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary kidney disease. Dr. Chebib's research focuses on defining mechanisms that drive cyst growth and translating those discoveries into innovative therapeutic strategies aimed at preventing and delaying kidney failure in people with ADPKD.
Dr. Chebib also is the principal investigator of the PKD Research and Therapeutics Laboratory. Dr. Chebib's laboratory has discovered previously unrecognized pathways in renal water handling and cystogenesis. Dr. Chebib and his team are actively engaged in developing novel small-molecule therapeutics targeting these pathways with the goal of advancing first-in-class treatments toward clinical testing.
In parallel, Dr. Chebib leads translational programs exploring gene-based therapeutic strategies for inherited kidney diseases. These efforts include developing gene therapy approaches aimed at reversing pathogenic mechanisms in polycystic kidney disease and using ex vivo kidney perfusion platforms to reprogram organs through targeted molecular interventions.
Dr. Chebib also maintains an active clinical research program bridging laboratory discoveries with patient care. He designs and leads investigator-initiated clinical trials and participates in multicenter therapeutic studies focused on disease-modifying strategies for ADPKD. His work integrates mechanistic biology, clinical phenotyping, imaging analytics and translational therapeutics to accelerate the development of precision medicine approaches for inherited kidney diseases.
As a recognized leader in ADPKD care and research, Dr. Chebib co-authored the U.S. practical guidance for the use of tolvaptan in rapidly progressive ADPKD and helped establish one of the earliest dedicated tolvaptan clinical programs in the United States. Through these efforts, he has contributed to the safe implementation of disease-modifying therapy in routine clinical practice.
Dr. Chebib is a strong advocate for patients with inherited kidney diseases and serves in several leadership roles within the PKD Foundation in the United States. He also advises multiple patient organizations internationally, supporting efforts to advance research and education and access to specialized care for people affected by polycystic kidney disease.
Focus areas
- Novel pathways of water regulation in ADPKD. Dr. Chebib investigates alternative mechanisms regulating renal water reabsorption that operate independently of vasopressin signaling. His laboratory has identified signaling pathways linking intracellular urate transport to aquaporin-2 trafficking and urinary concentration. These discoveries have opened new therapeutic opportunities and led to the development of small-molecule modulators now being evaluated in preclinical models with the goal of advancing first-in-class therapies for ADPKD.
- 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 studies how polycystin proteins regulate calcium flux and how disturbances in calcium-cAMP signaling promote cyst growth. His work also examines the contribution of ion channels and purinergic signaling pathways to cyst initiation and progression.
- Mechanotransduction and PKD progression. ADPKD is characterized by structural remodeling of renal tubules and impaired sensing of mechanical forces. Dr. Chebib studies the role of mechanosensitive ion channels and their interaction with the polycystin complex to understand how mechanical signals regulate cyst initiation and expansion. His laboratory has demonstrated that pharmacologic modulation of mechanosensitive pathways can suppress cystogenesis in experimental models.
- Genotype-phenotype relationships in ADPKD. Although ADPKD is a monogenic disorder, its clinical phenotype varies widely. Dr. Chebib leverages large clinical registries and detailed phenotypic datasets to define genotype-phenotype relationships across PKD genes. His work integrates clinical outcomes, imaging biomarkers and molecular data to better understand disease heterogeneity and to identify predictors of disease progression.
- Radiogenomics and AI-guided risk stratification. Dr. Chebib collaborates closely with radiologists and data scientists to develop and validate advanced imaging biomarkers and artificial intelligence tools (AI) for automated cyst segmentation and multiparametric disease progression modeling. By integrating imaging, genetic and clinical data, his team aims to create more precise risk stratification models that support personalized therapeutic decision making in ADPKD.
- Therapeutic innovation and clinical trial development. Dr. Chebib leads several clinical trials to address key unmet needs in ADPKD management. These efforts include the SereNDIpity-pb1phase 2 trial, which evaluated a repurposed therapy to mitigate aquaretic side effects associated with vasopressin receptor antagonists. His translational research aims to accelerate developing and implementing disease-modifying therapies for inherited kidney diseases.
- Gene therapy and kidney reprogramming. Dr. Chebib is developing novel gene-based therapeutic approaches for monogenic kidney diseases. His work explores the use of gene therapy and molecular editing strategies to correct pathogenic mechanisms underlying cystic kidney disorders. In parallel, he is advancing ex vivo organ perfusion platforms that enable targeted delivery of genetic and molecular therapies to human kidneys, with applications that include immune cloaking strategies and organ reprogramming aimed at restoring normal kidney function.
Significance to patient care
Dr. Chebib aims to prevent kidney failure in people with ADPKD and other inherited kidney diseases. His work brings together early diagnosis, each patient's personal risk, advanced imaging tools and new treatments. By connecting lab research with patient care, his goal is to create safer and better treatments that slow down the disease and improve quality of life.
Professional highlights
- Mayo Clinic:
- Director, Mayo Clinic Florida Polycystic Kidney Disease (PKD) Center of Excellence, 2022-present.
- Catalyst Award, 2023.
- New Investigator of the Year Award, 2023.
- Team Science Award, Mayo Clinic Robert and Billie Kelley Pirnie Translational Polycystic Kidney Disease (PKD) Center, 2020.
- Program chair, Polycystic Kidney Disease Medical Directorship Program, GlomCon Foundation, 2025-present.
- PKD Foundation:
- Board of directors, 2024-present.
- Co-chair, Centers of Excellence Advisory Committee, 2021-2024.
- Co-author, U.S. consensus guidelines on the use of tolvaptan in ADPKD, Journal of the American Society of Nephrology, 2018.