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Research | Overview

APOL1-associated kidney disease

Two genetic variants in apolipoprotein L1 (APOL1), common in Black individuals, result in greatly increased risk of focal segmental glomerulosclerosis (FSGS) and progression of chronic kidney disease in African-Americans. The mechanism of APOL1's kidney damage is unknown. Our lab is focused on conducting research that ultimately helps improve the health of patients with APOL1 kidney disease. We are using genetic epidemiologic approaches to discover the clinical impact that these risk variants have on both adults and pediatric patients. In parallel, we are using computational genomics to link genetic, epigenetic, and gene expression data to discover the mechanisms underlying the link between APOL1 genetic variants and FSGS.

Integrated, systems genomics of nephrotic syndrome

Our lab is pairing genome-scale genetic data with kidney tissue-derived gene expression and open chromatin data to discover novel genetic variants, or characterize known ones, associated with the pathogenesis and progression of nephrotic syndrome and other forms of chronic kidney disease. In doing so, we have created genomic variant databases and expression quantitative trait loci (eQTL) maps of glomerular and tubulointerstitial data and made these available to the community to empower parallel investigations.

Immunosuppressant sensitive nephrotic syndrome

The most common forms of nephrotic syndrome in children are those that respond to immunosuppressive medications, including steroids, calcineurin inhibitors, and rituximab. Recent genome-wide association studies by our group and others have discovered multiple independent loci associated with steroid sensitive nephrotic syndrome (SSNS). We are now interested in pursuing the functional role of these loci while also discovering new ones.

Mendelian nephrotic syndrome from a population perspective

Rare, pathogenic variants (“mutations”) in more than 40 genes are sufficient to cause Mendelian forms of nephrotic syndrome. Many of these “Mendelian NS genes” and their pathogenic variants have been discovered in patients with familial disease, from specific parts of the world, and with the most extreme phenotypes (i.e. steroid resistant nephrotic syndrome, FSGS). We are interested in understanding the prevalence of pathogenic variants in patients of diverse backgrounds with nephrotic syndrome as well as within the general population. Beyond prevalence, we are interested in genetic and non-genetic factors affecting the penetrance and expressivity of these variants for NS and proteinuric phenotypes.

Other areas of interest

  • return of research genetic testing results to nephrology patients
  • operationalizing genomic testing in the Pediatric Nephrology Clinic
  • genomic discovery using electronic health records and biobanks