About Our Research
Nephrotic syndrome is a rare kidney disease that results from damage in the kidney’s filtering units, called glomeruli. Our lab is specifically interested in how genetic changes can be linked with this disease. We can then use this knowledge to identify the molecular causes of NS and improve the prognosis and treatment of this rare disease.
We use computational genomics and bioinformatics to discover new, and map known, nephrotic syndrome-associated variants. We use systems genomics to integrate this genetic data with other genome-scale molecular datasets to try to understand the mechanisms linking these genetic changes with disease. We use epidemiology to discover the clinical consequences for patients carrying disease-associated genetic variants.
Our lab is equally committed to ethically and responsibly sharing genomic data. We firmly believe that widespread sharing in this way will allow for parallel genomic discovery efforts. And this will accelerate progress toward treatments and cures for nephrotic syndrome. You can find much of our data freely available for viewing and download at http://nephvs.org, https://nephqtl.org, http://apol1portal.org, and http://nephqtl2.org.
Some of our specific areas of interest
APOL1 Associated Kidney Disease
Our lab is focused on conducting research that ultimately helps improve the health of patients with APOL1 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. Unraveling the mechanisms of how APOL1 causes glomerular damage, and their modifiers and clinical consequences, are some of the most important current questions in nephrology. 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 systems genomics to link genetic, epigenetic, and gene expression data to discover the mechanisms underlying the link between APOL1 genetic variants and FSGS. Read our most recent paper for additional insights on APOL1 expression networks in the kidney here.
Immunosuppressant sensitive nephrotic syndrome
The most common forms of nephrotic syndrome in children are those that respond to immunosuppressive medications, including steroids, and second-line drugs. 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.
Integrated, systems genomics of nephrotic syndrome
We are pairing genome-scale genetic data with gene expression and open chromatin data from the kidney to discover specific genetic variants that influence the expression of specific genes in kidney cells. We can then link these genetic variants to kidney diseases and traits. We have created “high-resolution” expression quantitative trait loci (eQTL) maps of glomerular and tubulointerstitial kidney cells and made these available to the community on http://nephqtl2.org. Read more about our genomic kidney maps here.
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
