Two members of Dr. Harris' Kidney Disease Discovery Lab, dressed in white lab coats and standing in front of lab equipment, prepare samples for analysis.

Members of Dr. Harris' Kidney Disease Discovery Lab prepare samples for analysis.

Research

The Harris lab is investigating several types of kidney conditions.

Autosomal dominant polycystic kidney disease (ADPKD)

Our studies of ADPKD focus on genetic analyses of human disease populations and animal and cellular models:

  • Autosomal dominant polycystic kidney disease is known to be genetically heterogeneous, with PKD1 and PKD2 being the major genes. Our team recently used next-generation sequencing (NGS) approaches to identify other rare causes of ADPKD. More genes are now being sought.
  • Our lab uses an NGS panel of 356 genes for routine screening of people with PKD and ciliopathies. However, exome and genome sequencing are increasingly being used.
  • We're conducting genotype and phenotype studies to define genic and allelic effects.
  • Population studies using the Mayo Clinic Biobank are determining the penetrance of ADPKD genes.
  • Ultralow penetrant alleles such as PKD1: p.Arg3277Cys (RC) have been characterized. These can cause very early onset ADPKD through biallelic inheritance with a typical allele.
  • An animal model mimicking the RC allele (Pkd1rc/rc) has been generated and used for preclinical testing.
  • We're analyzing the trafficking and roles of the wild-type and mutant PKD proteins polycystin-1 and polycystin-2 in cellular and animal models of these conditions.
  • We're exploring genetic interactions among PKD genes.

Autosomal recessive polycystic kidney disease (ARPKD)

Our research on ARPKD focuses on genotype and phenotype studies and on the role of the protein product called fibrocystin. Our research includes:

  • NGS screening for people with ARPKD-like phenotypes and other recessive forms of polycystic kidney disease.
  • Analyzing trafficking and processing of fibrocystin.
  • Completing characterization of the phenotype of people with one mutant copy of the ARPKD gene, PKHD1.

Kidney ciliopathies

Our lab also is pursuing genetic and cellular studies of various kidney (renal) ciliopathies after the identification of genes for these conditions. These syndromic conditions are characterized by renal abnormalities, such as cysts, but often also have central nervous system, eye, digit and liver phenotypes.

Our research on kidney ciliopathies includes:

  • Screening for mutations in a wide range of ciliopathies using NGS approaches.
  • Analysis of renal ciliopathy animal models and interactions with simple PKDs.
  • Analyzing the phenotype in people who are monoallelic for syndromic PKD genes.

Kidney stones

Kidney stones are often the result of genetic, lifestyle and environmental factors. Some people, however, have monogenic kidney stone disease. This is a genetic condition caused by a gene mutation, with about 40 genes now known to play a role.

Our lab screens people suspected of having monogenic stone disease using an NGS panel of about 160 genes to identify the genetic causes. We correlate these genetic findings with the person's phenotype.