2025 Postdoctoral Fellowship

Understanding the Consequences of Targeting LRRK2’s Different Forms To Improve Future PD Treatments 

Genetic studies of Parkinson’s disease (PD) have identified several proteins key to disease risk. One of these proteins is called Leucine-Rich Repeat Kinase 2 (LRRK2), whose job it is to regulate the activity of various cell processes.  

Genetic variants of LRRK2 can be found in 1-5% of all PD cases. However, abnormal LRRK2 activity is often seen even in people without a clear genetic link to the disease, making the protein a strong target for designing novel treatments. Katy Surridge, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship, is broadening our understanding of LRRK2’s role in cells to improve PD treatment development. 

Like nearly all proteins, LRRK2’s activity is regulated by switching between an “off/open” and an “on/closed” state. The majority of research and treatments are focused on drugs that target LRRK2’s “closed” form, but evidence suggests that the protein’s “open” form may be a better therapeutic target in cells. Understanding how the use of different drugs with different mechanisms of action affects LRRK2’s role in cells is important for understanding both the normal function of the protein, and how best to target it for PD treatment. Dr. Surridge, under the mentorship of Samara Reck-Peterson, PhD, at Weill Cornell Medicine in New York City, has recently created tools that allow her to target and observe both forms of LRRK2 in cells, something that has not been directly studied before. 

“My research will use a newly designed toolkit of small molecules to study LRRK2’s endogenous interactome, localization, and the potential cellular consequences of therapeutic LRRK2 inhibition with different drug types” - Dr. Surridge 

Using these tools, Dr. Surridge will first explore LRRK2’s interactome – the collection of all the other proteins in the cell that interact with LRRK2. She will compare and contrast which proteins interact with LRRK2 in its open state vs. its closed state, highlighting which processes would be affected during different types of LRRK2 treatments. 

Next, Dr. Surridge will analyze the different pattern of modifications (phosphosites) on LRRK2 itself.  Evidence suggests that LRRK2 is modified differently in its different forms, and she hopes that by mapping these differences, she will identify novel features which can be used in both diagnostics and the design of new ways to specifically target the protein in future therapies. 

Dr. Surridge will then monitor how the protein’s localization within the cell changes depending on form. Previous studies have suggested that certain drugs may affect LRRK2’s localization in cells, and that this could impact other cellular processes. Dr. Surridge therefore expects to find closed-form LRRK2 in different parts of the cell than open-form LRRK2. 

These experiments will empower researchers to see and study LRRK2 in completely new ways, unlocking paths to new LRRK2-centered treatments of PD. When asked about how she feels about the fellowship and her upcoming research, Dr. Surridge said “I am delighted to receive this award from the Parkinson’s Foundation, which will help me to address a critical gap in knowledge in the field of LRRK2 cell biology, with potential to inform the future design of novel Parkinson’s disease therapeutics.” 

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

2025 Postdoctoral Fellowship

Creating Self-Folding Alpha-synuclein to Better Understand Parkinson’s 

A primary driver of Parkinson’s disease (PD) is the accumulation and spread in the brain of a misfolded form of a protein called alpha-synuclein. When misfolded, alpha-synuclein forms clumps called Lewy bodies that clog up brain cells called neurons. These clumps can cause other alpha-synuclein proteins to misfold as well, cascading the disruption as the disease progresses. 

Despite decades of innovation, conducting in vivo research (animal experiments, as opposed to cells in petri dishes) of alpha-synuclein in PD has been challenging. Getting alpha-synuclein to misfold in a way that mimics human PD in specific neurons on-demand is difficult, but Yujie Fan, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship, believes she has developed a new tool to accomplish this task.  

Under the mentorship of Viviana Gradinaru, PhD, at the California Institute of Technology in Pasadena, Dr. Fan designed a new technology for creating what she calls “self-assembling alpha-synuclein" (SAS) molecules. These SAS constructs are made of normal alpha-synuclein with attachments that allow researchers to trigger misfolding in cells on-demand. The SAS technology also allows Dr. Fan to pick specific cells in which the misfolding occurs, such as the dopamine neurons in the brain most affected by PD. Importantly, this tool overcomes many of the limitations that have hindered other research models of alpha-synuclein in PD.  

 “This award supports the development of an innovative tool named self-assembling synuclein (SAS) to model Parkinson's disease in a quantitative, inducible, tunable and cell-type-specific manner.”

- Dr. Fan 

Once the SAS tools have been fine-tuned and tested, Dr. Fan will implement them in mice to see if they can recreate alpha-synuclein misfolding and clumping like is seen in human PD. Her early results in mice show that the SAS model faithfully mimics many of the movement impairments commonly seen in people with PD, suggesting that her tools are working as expected. She will then test how alpha-synuclein misfolding in the gut might initiate PD-like symptoms, following recent research suggesting that PD could start in the gut. 

Refining and building upon this SAS technology will grant Dr. Fan and other PD researchers the ability to study the disease in new, more precise ways. The groundbreaking data and insights generated from these SAS experiments can lead to improved treatments and advance the field toward a cure for PD. 

Speaking on what this fellowship means to her and PD research broadly, Dr. Fan said “This award gives me the freedom and confidence to pursue bold, yet high-rewarding ideas. The insights gained from this work could help identify new treatment targets and improve how we test potential therapies. Ultimately, this research aims to bring us closer to stopping disease progression in PD.” 

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

2025 Postdoctoral Fellowship

Exploring the Neurochemistry Behind Parkinson’s-related Sleep Disruption 

The primary impact of Parkinson’s disease (PD) is a progressive loss of neurons in the brain that produce dopamine. Dopamine is a small signaling molecule used by neurons to relay messages and commands important for many tasks, including coordinated movement. As dopamine levels decline over time, the ability to perform these tasks decreases and manifests as PD symptoms. 

It was recently discovered that dopamine likely plays a critical role in regulating sleep. People with PD often experience disrupted sleep as an early symptom of the disease, which significantly impairs health even before movement symptoms begin. Xiaolin (Lindsay) Huang, PhD, a recipient of a Parkinson’s Foundation Postdoctoral Fellowship, is exploring the neurochemistry behind dopamine and sleep, generating new knowledge to guide future therapies that treat PD-associated sleep disruption. 

Research suggests that dopamine is important for waking up and staying awake. However, diminishing dopamine in PD does not lead to chronic sleepiness like this finding would suggest. Dr. Huang, under the mentorship of Yang Dan, PhD, at the University of California, Berkeley, is solving this puzzle by investigating how dopamine signaling coordinates with the “sleep pressure” molecule called adenosine, as well as how dopamine deficits affect a sleep-regulating region of the brain called the medial substantia nigra pars reticulata (mSNr). 

 “By uncovering the neural mechanisms driving PD-associated sleep disturbances, the study will shed light on a critical and underexplored aspect of the disease.” - Dr. Huang 

While dopamine promotes wakefulness, adenosine promotes sleepiness. Adenosine accumulates in the brain throughout the day and eventually overwhelms dopamine levels, leading to growing tiredness until it is time for bed. Using mice with and without simulated PD, Dr. Huang will utilize highly sensitive brain monitoring techniques to observe how PD affects the balance between dopamine and adenosine and how that disruption may impact sleep behaviors. 

Additionally, previous research from Dr. Dan’s lab has revealed that the mSNr region of the brain is important for regulating sleep-wake behaviors. Using the same experimental PD mice, Dr. Huang will assess if and how dopamine loss impairs neuron activity in the mSNr region, further disrupting sleep patterns in those animals. 

Altogether, these investigations into how PD-related sleep disruption are related to adenosine levels and mSNr changes can lead to future research and treatment development addressing this debilitating non-movement PD symptom. When asked what this award means for her work and career in PD research, Dr. Huang said “Receiving the Parkinson’s Foundation Postdoctoral Fellowship is both an honor and a pivotal step in my scientific journey. Ultimately, the findings may inform the development of new therapies to improve sleep and enhance quality of life for people living with PD.” 

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

2025 Postdoctoral Fellowship

Visualizing How LRRK2 Contributes to Parkinson’s

Several genetic variants have been identified that likely contribute to Parkinson’s disease (PD) progression. These variants typically alter the instructions for constructing proteins, the building blocks of the body.

Variants of the gene that create a protein called Leucine-Rich Repeat Kinase 2 (LRRK2) are found in 1-5% of all PD cases. Despite being the second most common PD-associated genetic variant, scientists are still unsure exactly how this altered LRRK2 protein causes or contributes to the disease biologically.

Tatyana Bodrug, PhD, a recipient of a Parkinson’s Foundation Postdoctoral Fellowship, will utilize a wide range of state-of-the-art microscopy and other visualization techniques to literally see how the LRRK2 protein acts in cells. By getting a clear picture of how LRRK2 interacts with other important cell processes, Dr. Bodrug hopes to advance the field toward more targeted and effective therapies.

Research suggests that LRRK2 plays a critical role in repairing lysosomes, the recycling centers of the cell whose dysfunction is closely linked to PD. Under the mentorship of Andres Leschziner, PhD, at Weill Cornell Medicine in New York City, Dr. Bodrug will first use a technology called cryo-electron microscopy (cryo-EM) to take incredibly zoomed-in, high-resolution images of LRRK2 as it interacts with lysosomes to see this biological process at a previously unmatched level.

“This integrative approach will reveal a deeply contextualized view of how LRRK2 is activated at the lysosome to better understand how mutations in LRRK2 lead to PD.” - Dr. Bodrug

This technology will also allow Dr. Bodrug to visualize what other proteins interact with LRRK2. Understanding the distinct biological components affected by LRRK2 could lead to new targets for PD treatment.

To investigate these components further, Dr. Bodrug will use a technique called dynamic mass photometry (dynamic-MP) to witness how LRRK2 associates with a group of proteins called “Rab” proteins. These Rab proteins are modified by LRRK2 and may themselves be involved in PD. This dynamic-MP technology allows individual LRRK2-Rab interaction events to be directly tracked in real time, an impressive technological achievement that is likely to advance the field.

By combining these various cutting-edge imaging procedures, Dr. Bodrug hopes to capture valuable insights into LRRK2 that could break new ground and lead to improved treatments of LRRK2-linked PD. Speaking on the impact of this fellowship, she said “Receiving this award allows me to more broadly explore the mechanisms that underlie Parkinson's disease. Our hope is that this will lead to a clearer understanding of the complexities involved in LRRK2-associated Parkinson's disease and better therapeutics.”

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

2025 Postdoctoral Fellowship

Reclaiming Restful Sleep by Unraveling How Parkinson’s Changes the Brain 

Along with the typical movement-related symptoms, many people with Parkinson’s disease (PD) also experience other non-movement health issues. These non-movement symptoms can be quite debilitating and sometimes more difficult to notice by care partners. 

One common non-movement PD symptom is difficulty sleeping, often in the form of waking up frequently throughout the night. Pamela Marcott, MD, PhD, a recipient of a Parkinson’s Foundation Postdoctoral Fellowship, is casting a spotlight on the sleep-associated circuits of the brain to understand how exactly PD impacts sleep patterns. By uncovering the mechanisms behind PD-related sleep problems, she hopes to help advance new therapies for such disturbances. 

While much of the neuroscience of sleep is still a mystery, researchers do know that staying asleep through the night requires a highly calibrated balance of different signals in the brain. These sleep signals are relayed through brain cells called neurons and can vary in frequency and intensity, depending on their purpose. If these signals become altered and imbalanced, sleep fragmentation occurs with "frequent changes between different sleep and wake states, leading to less consolidated and restful sleep,” said Dr. Marcott. 

Under the mentorship of Alexandra Nelson, MD, PhD, and Ying-Hui Fu, PhD, at the University of California, San Francisco, a Parkinson’s Foundation Center of Excellence, Dr. Marcott is investigating how PD changes the behavior of neurons in a specific sleep-regulating region of the brain called the pedunculopontine nucleus (PPN). PPN neurons act like telephone operators, relaying important signals across the brain. Using mice with and without PD-like symptoms, she will measure how the disease affects the ability of PPN neurons to transmit their important sleep signals. 

“Results of this study will improve our understanding of the circuit mechanisms that regulate sleep disturbances in PD, which will inform future therapeutic treatments.” - Dr. Marcott 

After learning more about how PD changes the sleep-related neurons’ signaling ability, Dr. Marcott will then monitor the brains of the mice as they sleep. She will keep a close eye on how the PPN neurons activate during sleep phase transitions, as she believes PD causes these neurons to be overactive and lead to fragmented sleep. Observing in real time how PD alters sleep regulation in the brain will provide a strong foundation for understanding how to treat this symptom and give restful nights back to people with PD. 

 “As a physician scientist in this space I am committed to making meaningful discoveries in the laboratory that will benefit my patients, and I am excited to have the opportunity to start this phase of my career with the support of the Parkinson's Foundation,” said Dr. Marcott. 

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

2025 Postdoctoral Fellowship

Leveraging AI to Decode the Genetics Behind Parkinson’s 

Parkinson’s Foundation research has found that approximately 13% of people with Parkinson’s have a genetic link to the disease. PD-associated DNA mutations affect the production and function of critical proteins, potentially contributing to disease risk or symptom progression. While many high-profile PD-associated mutations have been discovered in genes such as LRRK2, GBA, and SNCA, Jeff Kim, PhD,  recipient of a Parkinson’s Foundation Postdoctoral Fellowship, is taking the field further by using artificial intelligence (AI) to: 

1. Understand how overlapping types of PD mutations can affect the chances of developing PD. 

2. Dig deeper into the genetic data to find more subtle, hidden mutations that might impact the risk for developing PD. 

At first, genetic studies of PD were focused on finding rare single mutations most associated with disease. As techniques improved, researchers have been able to roughly measure the risk of developing PD by adding up the risk from multiple common mutations. However, “while we know that both rare gene mutations and combinations of common genetic variations can cause PD, we rarely study how these two types of genetic risk work together or change with age,” said Dr. Kim. 

With his colleagues in the lab of Dr. Joshua Shulman at the Baylor College of Medicine a  Parkinson’s Foundation Center of Excellence, in Houston, Texas, Dr. Kim is utilizing a new statistical tool called the “Causal Pivot Model” to better understand the complexities of PD mutation combinations. This model works on a simple principle: people with PD with rare single mutations usually don't have many common mutations. By looking at this pattern, the model can spot people who likely carry hidden rare single mutations that haven't been found yet. Dr. Kim is also building age into the model, since some mutations cause PD early in life while others strike later - this could help identify people at risk for early-onset disease. 

Once the model has been tested and trained on enough data, Dr. Kim’s next goal is to combine the Causal Pivot Model with an advanced AI model called AI-MARRVEL to identify hidden potential PD mutations, ones that have been overlooked in previous analyses but can be spotted by this powerful tool. These mutations can then be tested in fruit flies, observing if they cause Parkinson’s-like symptoms and leading to novel therapeutics in the future. 

Thinking beyond the data and computations, Dr. Kim is clear-eyed about the potential impact his AI-powered modeling could have for people with PD. 

“Ultimately, this project aims to move us closer to clinically useful genetic information that could eventually guide personalized treatment strategies for people with Parkinson's disease,” said Dr. Kim. 

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

2025 Clinical Research Training Scholarship in Parkinson’s Disease

Using Brain Scans to Understand what Causes Parkinson’s-related Dystonia

Many people with Parkinson’s disease (PD) experience dystonia — sustained or repetitive muscle twitching, spasms or cramping that can occur in different parts of the body. These involuntary movements are often more forceful and painful than those of dyskinesia, a potential side effect of some PD medications that are involuntary, erratic movements that can either be fluid, rapid or extended muscle spasms.

Developing effective treatments for PD-related dystonia is difficult because we don’t know a lot about the neuroscience behind the condition. Laura de Lima Xavier, MD, recipient of the 2025 Clinical Research Training Scholarship in Parkinson’s Disease funded by the Parkinson’s Foundation and the American Brain Foundation, in collaboration with the American Academy of Neurology, is comparing brain scans of people with PD with and without dystonia to identify the key brain regions involved in dystonia to search for better therapeutic options.

“These efforts aim to significantly improve diagnostic tools, treatment strategies, and overall quality of life for individuals suffering from PD-related dystonia,” said Dr. Xavier.

Working as a neurologist and movement disorders fellow at Washington University in St. Louis, MO, Dr. Xavier believes that the key to understanding PD-associated dystonia lies with resting state functional MRI (rs-fMRI) scanning. This technology highlights how different regions of the brain are connected, and has already been used to better understand isolated dystonia in people without PD.

Dr. Xavier will compare rs-fMRI data that was previously collected from people in the PD community with and without dystonia, focusing on the sensorimotor network (SMN) area of the brain responsible for coordinating movement.

Identifying which regions in the SMN activate differently in people with dystonia could lead to future treatments that target those regions and alleviate the symptom.

“Future research will include examining different types of PD-related dystonia and using these insights to develop better treatment options,” said Dr. Xavier.

Dr. Xavier is grateful for the support she received to make this research possible and is optimistic about its potential to make a difference for people with PD.

“At a time when funding is scarce and the demand for clinicians and scientists trained in movement disorders is increasing, this support is invaluable. It provides me with the resources necessary to delve deeply into the mechanisms of PD-related dystonia, ultimately driving improvements in clinical care for those affected by Parkinson's.” - Dr. Xavier.

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