My PD Story

2026 Launch Award

Building Stem Cell Models to Study Dopamine Neuron Vulnerability in PD

In Parkinson’s disease (PD), dopamine neurons in the midbrain break down over time, leading to progressively worsening symptoms. However, not all dopamine neurons are affected the same — some remain healthy, while others break down. This selective vulnerability of dopamine neurons has baffled scientists for decades and remains a major unanswered question in the PD field. 

Donghe Yang, PhD, recipient of a Parkinson’s Foundation Launch Award, is determined to investigate what differentiates dopamine neurons that die off in PD and those that seem unaffected. By understanding what makes certain neurons uniquely fragile, we can explore new ways to biologically reinforce them and protect them against PD.

“My research aims to uncover why the neurons most affected in PD are uniquely vulnerable and to use that knowledge to guide better treatments for patients.” – Dr. Yang

In Parkinson’s disease, a specific type of dopamine neuron in the substantia nigra (called A9 neurons) are lost. Meanwhile, closely related dopamine neurons (called A10 neurons), located in the directly neighboring brain region, do not degenerate in the same way. While similar biologically, Dr. Yang has uncovered subtle yet important differences between A9 and A10 neurons that could be the key to their differing fragility.

Within the lab of Dr. Lorenz Studer, at the Memorial Sloan Kettering Cancer Center in New York, Dr. Yang has used these clues to develop a blueprint on how to turn stem cells directly into  A9 or A10 neurons in petri dishes — a remarkable feat for which a provisional patent has been filed. 

Using complex tools, Dr. Yang will validate that this process can create authentic A9 and A10 neurons consistently. Dr. Yang will also transplant these neurons into mice brains to ensure that they integrate properly, ensuring their health and testing their potential to be used for future dopamine neuron transplantation approaches.

With these generated A9 and A10 neurons, Dr. Yang will then use them as a new model of PD, altering them to have PD-related genetic variants. By observing how the different neuron types react to these genetic changes, he can better understand what makes the A9 neurons more vulnerable and the A10 neurons more resilient to PD. 

Dr. Yang will also simulate aging in these neurons, further exploring how aging and PD-related variants result in A9 neuron breakdown while A10 neurons stay functional.

Finally, Dr. Yang will create a simulated midbrain using the A9 neurons and other immune cells. He will induce inflammation in this simulated midbrain, collecting more data on how A9 neurons react to biological stress, which could contribute to their breakdown.

The ability to grow distinct populations of A9 and A10 neurons creates a new, unique, and valuable model in which to study PD. With many advantages over previous approaches, these experiments will establish an important foundation from which PD scientists can explore A9 neuron vulnerabilities, leading to future therapies and treatments that prevent dopamine neuron degeneration. 

“This award gives me strong encouragement to continue my work on Parkinson’s disease and to pursue research that may one day help people living with this condition,” said Dr. Yang. “This work could help identify new ways to protect vulnerable brain cells, as well as develop better disease models and future cell-based therapies.”

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers.