Research

Generation and Repair of the Kidney

The mammalian kidney plays a central role in controlling the environment for all the body's systems, regulating blood pressure and blood composition, and removal of waste from metabolic processes. The functional unit is a nephron: up to one million nephrons are formed in the human kidney during fetal life when the supply of nephron stem/progenitor cells is exhausted. Consequently, repair of kidney damage is quite different from that of many other organ systems where stem cells remain in place throughout life. Our research on the developing kidney focuses on identifying the regulatory processes that maintain, expand and differentiate kidney stem cells to the mature cell types of the functional kidney. In the adult, we are identifying the cellular and molecular mechanisms at play in repairing damage on acute injury. These lines of research will enable complimentary strategies to treat kidney injury and disease.

Optical projection tomography (OPT) imaging of ductal networks and nephron stem/progenitor cells in the developing mouse kidney

Credit: Kieran Short, Robert Kao, Andrew McMahon and Ian Smyth

Mouse kidney culture for 24 hours, embryonic day 13.0. The red fluorescent protein (RFP) is expressed by the uteric bud cells (Wnt11). The green fluorescent protein (GFP) is expressed by the nephron progenitor cells (Six2).

Credit: Odyssé Michos

Optical projection tomography (OPT) imaging of an embryonic day 12.5 kidney stained with cytokeratin (orange) and Six2 (blue)

Credit: Lisa Rutledge and Seth Ruffins

The functional unit of the human kidney is a nephron, which arises from the renal vesicle (gold) formed by streams (red) of nephron progenitor cells (green). The renal vesicle transitions through an S-shaped intermediate (green/orange/pink), forming the nephron's tubular network (white).

Credit: Nils Lindström, Andy McMahon, Seth Ruffins and the Microscopy Core Facility at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC

Mouse kidney culture for 28 hours, embryonic day 13.0. The red fluorescent protein (RFP) is expressed by the nephron progenitor cells (Cited1). The green fluorescent protein (GFP) is expressed by the uteric bud cells (HoxB7 promoter).

Credit: Odyssé Michos

Optical projection tomography (OPT) imaging of an embryonic day 13.5 kidney stained with cytokeratin (grey) and Six2 (red).

Credit: Lisa Rutledge and Seth Ruffins

Mouse kidney culture for four days, embryonic day 11.5. The green fluorescent protein (GFP) is expressed under the HoxB7 promoter (ureteric bud cells). A frame was taken every hour for four days..

Credit: Odyssé Michos