SUMMARY
Nephrology researcher Peter C. Harris, Ph.D., studies genetic diseases of the kidney, including polycystic kidney disease (PKD) and autosomal dominant polycystic kidney disease (ADPKD). Polycystic kidney disease includes a range of inherited disorders that often results in renal failure and even death.
Dr. Harris' studies focus on screening for genes and specific variants that can cause PKD. He also uses genotype and phenotype studies to determine the extent to which variability in disease presentation and progression is explained by genic and allelic factors.
Dr. Harris is principal investigator of the Polycystic Kidney Disease Discovery Laboratory. The lab uses several genetic and cell biological approaches to understand the etiology and pathogenesis of these kidney disorders. His lab develops and uses animal models to study pathogenesis and for preclinical testing. His lab also investigates monogenic kidney stone diseases through genotype and phenotype studies. Dr. Harris' research is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Department of Defense Congressionally Directed Medical Research Program.
Dr. Harris also is the director of the Mayo Clinic Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center. In addition, Dr. Harris hosts the PKD Foundation-funded ADPKD Mutation Database, which describes more than 2,000 variants of ADPKD genes.
Focus areas
- Developing murine models of PKD genetics. To better understand the function of proteins encoded by PKD genes, Dr. Harris has generated mouse models that eliminate, reduce and increase expression of PKD genes. The Pkd1RC hypomorphic model has been used extensively for preclinical testing.
- Identifying new genes for ADPKD. Through next-generation sequencing approaches and large populations of people with ADPKD, Dr. Harris' lab screens for new causes of ADPKD. This work has led to the identification of three new ADPKD genes in the past decade.
- Testing the penetrance of ADPKD genes and specific variants. Using the Mayo Clinic Biobank, Dr. Harris and his research team are determining how often pathogenic changes in various PKD genes cause cyst development and kidney failure.
- Analyzing polycystin-1 processing. PKD is associated with defects of primary cilia. Dr. Harris' team is analyzing the processing of the large, membrane-bound ADPKD-related protein called polycystin-1. This work includes cleavage, glycosylation and trafficking, and determining how specific pathogenic changes disrupt this processing.
- Understanding disease pathogenesis. Dr. Harris studies the role of the autosomal recessive PKD protein, called fibrocystin, and the MKS protein, called meckelin. Analysis of mutant products also helps scientific understanding of disease pathogenesis.
Significance to patient care
Dr. Harris' research is improving diagnosis and prognosis for PKD and related kidney disorders and may lead to new treatment options. His laboratory uses advanced DNA sequencing methods to identify causative variants and even new genes that cause ADPKD. This information increases the number of people who can obtain an ADPKD genetic diagnosis. Dr. Harris' work with large populations also has contributed knowledge that enables better clinical monitoring of disease course and progress.
Professional highlights
- Mayo Clinic:
- Gordon H. and Violet Bartels Professor of Cellular Biology, 2024.
- Director, Mayo Clinic Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, 2021-present.
- Team Science Award, 2020.
- Homer W. Smith Award, American Society of Nephrology, 2008.
- Inaugural Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease, PKD Foundation and International Society of Nephrology, 2003.