Our Research Explained

Recreating the Unreachable

The Challenge: A Hidden Network

The peripheral nervous system is like a vast network of wires connecting your brain to your organs. These nerves allow us to feel the world, manage stress, and keep our organs running automatically by controlling heart rate, pain, temperature, and pressure.

However, studying diseases of this system—known as peripheral neuropathies—is incredibly difficult. Imagine trying to understand a malfunction when the most important cells involved are deep inside the body, impossible to reach, and unsafe to remove from a patient.

The Solution: Building a “Living Window”

At the Zeltner Lab, we approach this challenge differently. Instead of trying to take neurons from patients, we grow them.

We use human pluripotent stem cells—cells that have the potential to become any cell in the body—and follow precise “recipes” to transform them into the specific neurons affected by real human diseases. By doing this, we create a tiny, living window into the human body. This allows us to study the defects of individual patients in a petri dish, opening the door to personalized care.

Familial Dysautonomia (FD)

To understand the power of this approach, we can look at our work on a rare and devastating disease called Familial Dysautonomia (FD).

FD primarily affects the peripheral nervous system in children. In these patients, neurons fail to form properly and die over time. This leads to life-threatening symptoms, including:

  • Inability to regulate heart rate and blood pressure

  • Severe vomiting episodes

  • Inability to feel pain or heat

Because we cannot extract these dying neurons from children to study them, we recreated them in the lab using stem cells.

The Discovery: A Faulty “Safety Blanket” Through our stem cell models, we discovered a critical defect that had never been seen before. The extracellular matrix—which acts as a support system and “safety blanket” around the cells—is faulty in FD patients. Without this proper support, the neurons die.

The Potential Cure: Genipin Once we identified the broken support system, we looked for a way to fix it. We found that a compound called genipin, historically used in medicine, can repair the extracellular matrix. In our petri dishes, genipin acts on the support system to fix the defects, allowing the neurons to survive.

This project lays the foundational work for using genipin to treat children with FD and possibly other peripheral neuropathies.

The Broader Impact

FD is just one example of how we are rewriting the stories of nervous system disorders. In the Zeltner Lab, we use this same technology to generate various cell types to study different conditions:

  • Sensory neurons for pain and touch disorders.

  • Autonomic neurons for heart and digestion regulation.

  • Sympathetic neurons for the “fight-or-flight” response.

  • Adrenal gland organoids for stress hormone control.

By bringing together stem cell science, neuroscience, and engineering, we aim to read these cellular stories and help write better endings for patients.