Research Information
Research Interests
Innate Immune Activation and Podocyte Injury in Diabetic Kidney Disease:
The number of individuals with diabetes is expected to exceed 690 million worldwide in the next 20 years. Diabetic kidney disease (DKD), defined as the coexistence of chronic kidney disease (CKD) and diabetes, affects nearly 35% of diabetic patients and accounts for up to 50% of end-stage kidney disease (ESKD) cases.
This project investigates how metabolic stress and mitochondrial dysfunction in diabetes activate innate immune pathways and drive proinflammatory cytokine production in glomerular cells. We integrate data from diabetic animal models with multiomics datasets from DKD patients obtained through the Kidney Precision Medicine Project.
The goal is to identify molecular subtypes that explain part of the heterogeneity in DKD mechanisms and to define patient groups that may benefit from targeted therapies.
Pathogenesis of APOL1-associated Kidney Diseases:
Chronic Kidney Diseases (CKD) are common among African American patients. The excess risk for CKD in this population is largely explained by social determinants of health and by the presence of genetic variants in the APOL1 gene that are unique to African ancestral populations. The pathogenic mechanisms responsible for the genetic association remain poorly understood. Most importantly, the lack of consensus on the mechanisms by which APOL1 risk variants induce kidney diseases hinders the development of specific therapies.
Our major focus is to study glomerular and single-cell transcriptomes from kidneys and organ models to uncover transcriptional phenotypes associated with the presence of APOL1 kidney risk variants. Our goal is to extract gene signatures that could inform about the pathobiology of APOL1, and help to identify potential therapeutic agents.
Research Projects
Using transcriptomics and ex vivo organotypic models to discover mechanisms of APOL1-associated podocytopathies
Chronic kidney disease (CKD) is a progressive disease that results in the gradual loss of kidney function over time, leading to kidney failure and a need for dialysis or kidney transplantation. CKD is a leading cause of morbidity and mortality in the United States, affecting near 15% of the adult population, and imposing an important economic burden on the healthcare system. Moreover, CKD contributes to health disparities as certain minorities including African Americans, Hispanics, and Native Americans, have a higher prevalence of this disease.
Among African Americans, a substantial part of the excess risk for CKD is explained by the presence of genetic variants in the APOL1 gene that are unique to African ancestral populations. However, the exact mechanisms responsible for this genetic association remain unclear, hindering the development of specific therapies. To address this issue, our research focuses on studying the glomerular and single-cell transcriptomes of kidneys and organ models to identify transcriptional phenotypes associated with APOL1 kidney risk variants. By extracting gene signatures, we aim to better understand the pathobiology of APOL1 and identify potential therapeutic agents.
Crosstalk between visceral and parietal cells of the glomerular epithelium in proteinuric diseases
Chronic kidney diseases (CKD) are a major public health problem. Forty million Americans live with kidney diseases, and nearly 700,000 have evolved to end-stage kidney disease (ESKD). Importantly, advanced CKD constitutes a racial and ethnic disparity as different glomerulopathies, including Focal Segmental Glomerulosclerosis (FSGS) and hypertension-attributed-ESKD (H-ESKD) are much higher in minorities. The kidney glomerulus is a tuft of small blood vessels located at the beginning of the nephron that controls the filtration of blood into Bowman’s space to form urine. At the visceral side of Bowman’s space, surrounding the tuft, are the podocytes, which play a critical role in maintaining the filtration barrier. The parietal side of Bowman’s space is lined by parietal epithelial cells (PECs). Several podocytopathies are characterized by podocyte dedifferentiation, diffuse foot processes and loss of the slit diaphragm resulting in heavy proteinuria. Even though podocyte effacement is a hallmark of proteinuric diseases, the interaction between this cell type and PECs during proteinuria and remission remains obscure. Injection anti-nephrin antibodies to rodents causes a redistribution of slit-diaphragm proteins similar to that observed in kidney biopsies of patients with nephrotic syndrome, which results in proteinuria and lesions compatible with FSGS. We will use this model to conduct histological and transcriptional studies at single cell resolution to determine whether the restoration of the epithelial cell continuum during proteinuria and remission involves the replacement of podocytes by PECs.