Active Research

Mission - Vision - Focus

Our mission is to limit kidney injury and enhance kidney repair/regeneration.
Our vision is to translate our basic science research findings to address clinically relevant
questions that will ultimately improve the lives of people with kidney disease.
Our focus is on the kidney glomerulus in health, aging, and disease.

Background: Glomerular diseases are the leading cause of chronic

and end-stage kidney disease. A loss of podocytes is a major cause

of glomerular scarring, leading to decreased kidney function.

Podocytes are post-mitotic glomerular epithelial cells and

therefore cannot self-renew when they are lost in disease and

aging.

Rationale for our studies: We are focused on two candidate

progenitor/stem cell populations – parietal epithelial cells and cells

of renin lineage – to replace depleted podocytes and enhance

repair of the injured glomerulus.

Experimental approaches: We use single and dual reporter

mice for cell lineage tracing. We utilize unique mouse models of

podocyte injury. We isolate cultured primary and immortalized

podocytes, parietal epithelial cells, and cells of renin lineage to

conduct co-culture approaches utilizing microfluidic devices. We

perform transcriptome analysis on isolated podocytes and by

single nuclear RNAseq.

Background: With increased life expectancy, the number of Americans aged 65 years and older will more than double over the next 4

decades. Kidney function, measured by glomerular filtration rate, decreases ~0.8-1.0% per year after age 40. This decreases the kidney’s

nephron reserve in the middle-aged and elderly, should they develop glomerular disease. Thus, it is of little surprise that the risk,

incidence, and prevalence of chronic kidney disease are strongly linked with advancing age. As a result, elderly patients are now the largest

group undergoing chronic dialysis for the first time.

Rationale for our studies: Our focus is on restoring the podocyte’s life- and health-span in the aged kidney when further compromised by

superimposed disease, and on reducing aged effects on neighboring parietal epithelial cells.

Experimental approaches: We have generated transgenic and mutant mice to study specific pathways that are perturbed in the aged

podocyte. We pharmacologically target pathways in mice that are increased in aged podocytes and parietal epithelial cells. We

superimpose glomerular disease on middle-aged and aged mice. We isolate podocytes and parietal epithelial cells from young and aged

mice for cell culture studies. We analyze transcriptomic changes over the life of mice using single nuclear RNAseq. We translate our

experimental results to the human kidney.

Background: Current oral and intravenous therapies given to patients with kidney disease are not cell type-specific, leading to unwanted

side effects.

Rationale for our studies: Our focus is to develop strategies to deliver drugs and small molecules specifically to glomerular podocytes and

parietal epithelial cells in disease.

Experimental approaches: We are using nanobody and nanoparticle strategies in collaboration with Lumen Biosciences Inc and Dr. Suzie

Pun respectively.