Research Projects

Due to its enormous complexity, the kidney has an abundance of gene and protein interactions that have yet to be discovered. Our lab has a diverse array of research projects ranging from mechanisms of tubule formation and regeneration to glomerular development and disease. Using in vivo and in vitro models that encompass cell biology, genetics, bioinformatics, physiology and cutting-edge 3D imaging approaches, we analyze the molecular functions and subcellular structure of individual cell types within the kidney in healthy and disease states.

Mechanisms of tubule formation and regeneration

A fundamental question in developmental and cell biology is: How do a group of cells orchestrate the complex changes, including proliferation, migration, sorting, and differentiation to form a polarized tubule? Tubule formation is essential to the normal development of many organs including kidney, blood vessels, lung, pancreas. Congenital defects in tubule formation lead to a variety of human diseases, including various kidney diseases. We are interested in discovering the basic cellular and molecular mechanisms that drive early tubule formation in the developing embryo and understanding how these same mechanisms promote tubule repair in regenerating tissue.

Studies of glomerular development and disease

Left: Wild-type; Right: Nephronectin mutant glomeruli

Glomeruli are the filtration units of the kidney, containing three major cell types that function in concert to ensure the health and dynamic function of blood filtration. Defects in glomerular structure and function are a major cause of congenital and acquired kidney failure, underlying common diseases such as diabetic kidney disease. Our laboratory is studying the complex functional and structural interplay amongst these cell types in development, maintenance, and disease. One specific area of focus is the protein nephronectin and its receptor, alpha8 integrin, which are misregulated in common glomerular diseases and also a cause of congenital kidney disease.

Connecting bioengineered tubules to failing kidneys

Our laboratory is a member of the ReBuilding a Kidney Consortium funded by the NIH. A main purpose of this consortium is to induce stem cells to become kidney progenitor cells that will grow, differentiate, and organize to form small, organ-like structures (called organoids) that can be implanted under the capsule of failing kidneys to improve their function. Currently, a major obstacle in the field is that implanted kidney organoids do not connect with the tubules of the host kidney, and thus, do not improve their function. Our laboratory aims to discover how tubules normally interconnect and devise novel strategies that promote tubule-tubule connections.