Thong C. Ma, PhD

I study Parkinson's disease (PD) and multiple system atrophy (MSA), two related neurodegenerative movement disorders characterized by the abnormal accumulation of α-synuclein protein.  

In PD, α-synuclein accumulates primarily in neurons and contributes to their dysfunction. The symptoms of PD are caused by the death dopamine-producing neurons and loss of this essential neurotransmitter and is most often treated by “replenishing” dopamine with the drug levodopa. While highly effective, levodopa therapy can cause troubling abnormal movements known as levodopa-induced dyskinesia (LID). Our group studies how brain circuitry is changed by the loss of dopamine to cause PD symptoms and how treatment with levodopa causes LID. We focus on regulating the activity of specific neuron types in brain regions affected by PD with the goal of finding specific manipulations that prevent or reverse LID.  

In MSA, α-synuclein abnormally accumulates in oligodendrocytes, an important non-neuronal supportive brain cell type. Dysregulation of oligodendrocytes ultimately leads to neuron death, causing the symptoms of MSA. My research seeks to understand how cellular physiology is dysregulated in MSA using single nucleus RNA sequencing of MSA brain cells. With this, we can measure differences in gene expression to infer the pathways that are altered in MSA, providing insight on the potential pathogenic processes that may be targeted for therapy.

To complement these approaches, we also work on biomarker discovery and development to identify ways to diagnose PD and MSA at earlier stages and to measure disease progression.