Cellular Trafficking & Polycystic Kidney Disease - The Caplan Lab at Yale School of Medicine

Why It Matters

Identifying and targeting the cellular mechanisms of PKD could deliver the first disease‑modifying therapies for millions of patients, while deepening fundamental knowledge of epithelial biology.

Key Takeaways

• Epithelial cells maintain barrier and selective transport via apical/basolateral polarity.
• Lab studies protein targeting mechanisms in kidney epithelial cells.
• Research investigates molecular functions of polycystic kidney disease (PKD) genes.
• Team explores small‑molecule and gene‑therapy approaches for PKD treatment.
• One therapy entered clinical trials; another poised for human testing.

Summary

The Caplan Lab at Yale School of Medicine focuses on how kidney epithelial cells organize their apical and basolateral domains to control barrier function and selective transport. By dissecting the role of tight junctions and protein‑targeting pathways, the group aims to map the cellular architecture that underlies normal renal physiology.

Using immunofluorescence, electron microscopy, and protein biochemistry, researchers have identified how proteins encoded by polycystic kidney disease (PKD) genes operate at the molecular level. The lab distinguishes two research streams: one that elucidates the physiological function of PKD proteins, and another that screens for therapeutic vulnerabilities, including small‑molecule inhibitors and gene‑editing strategies.

A notable outcome is the development of a candidate therapy now in human clinical trials, with a second candidate slated for trial entry. The team’s holistic approach—integrating microscopy, molecular analysis, and functional assays—provides concrete examples of translating basic cell biology into potential treatments.

If successful, these efforts could reshape PKD management by delivering disease‑modifying drugs, while also advancing broader understanding of epithelial trafficking mechanisms that are relevant to many organ systems.

Original Description

For more information on Michael Caplan or #YaleSchoolOfMedicine, visit: https://medicine.yale.edu/profile/michael-caplan and https://medicine.yale.edu/lab/caplan.

In the Caplan lab, they use a variety of modern techniques to study Cell Biology, Epithelial Cells, the Kidney, Polycystic Kidney Diseases, Physiology, and Ion Pumps.The surface membranes of epithelial cells are divided into domains characterized by dramatically different protein compositions. Membrane proteins whose distributions are restricted to one of these domains must incorporate information that specifies their appropriate destinations. They seek to determine how this information is encoded and how it is interpreted. The Caplan Lab studies of cellular trafficking focus on proteins involved in ion transport, as well as on the proteins associated with polycystic kidney disease. Polycystic kidney disease is a prevalent and serious genetic disorder that distorts the normal architecture of renal epithelial cells and that is a major cause of kidney failure. The Caplan laboratory is working to understand the mechanisms responsible for this condition and to identify targets for new therapies.

0:00 The Caplan Lab

0:53 What are they studying?

1:47 How are they studying it?

2:27 Where might this research lead?