Mariana Monje, MD, PhD 

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Investigator Bio:   

Dr. Mariana Monje is a physician-scientist with specialized training in movement disorders. She earned her medical degree and completed her neurology residency at the Universidad Autónoma de Madrid, where she also pursued a PhD in neuroscience investigating the dopaminergic innervation of the thalamus in a primate model of Parkinson’s disease (PD). She subsequently expanded her research expertise through advanced cell biology training as a postdoctoral scholar in Dr. Dimitri Krainc’s lab at Northwestern University, where she also completed her fellowship training in movement disorders. 

Currently, Dr. Monje serves as an Instructor in Neurology at Northwestern University. Her research bridges clinical practice and basic science, integrating systems neuroscience with in vivo and in vitro models of PD to better understand disease mechanisms and therapeutic strategies. 

Objectives/Background:

Recent studies have found that a protein called GPNMB is elevated in the blood of people with PD. Genetic studies also suggest that higher levels of GPNMB can increase the risk of developing the disease. Interestingly, GPNMB levels are also high in patients with diseases linked to problems in the lysosomes, which are parts of the cell that help get rid of waste material. This protein can be released by the cells and help them communicate with each other. However, we do not fully understand how and why this protein is released from the dopaminergic neurons and how it contributes to PD. 

We aim to understand why the GPNMB protein accumulates, how it is released by the dopamine-producing neurons affected in PD, and how high levels of GPNMB affect those neurons. 

Methods/Design:

To answer these questions, we are studying GPNMB using two different cell types: common lab cells and dopamine-producing neurons derived from healthy people and from people with a specific genetic mutation (GBA1) that increases the risk of PD. Neurons with this mutation have problems in their lysosomes, leading to waste buildup. This model allows us to study GPNMB in human cells that mimic both healthy and PD-affected brains. We will investigate the relationship between high GPNMB levels and lysosomal dysfunction in these brain cells, as well as how this dysfunction can lead to the release of GPNMB. We will also study how high levels of released GPNMB affect the function of neighboring cells, which may contribute to the progression of PD. 

Relevance to Diagnosis/Treatment of Parkinson’s Disease:

Since GPNMB levels are found to be higher in the blood of individuals with PD, our research could lead to using GPNMB as a biomarker of the disease. By fully understanding the role of GPNMB, it may also help developing new treatments that could reduce its harmful effects, potentially alleviating the progression of PD.