2022 Postdoctoral Fellowship 

Utilizing Lampreys to Explore New Drug Target for Parkinson’s

Cristina Roman-Vendrell, PhD, from the Marine Biological Laboratory is utilizing an invasive species from the Great Lakes to further Parkinson’s disease (PD) research. She received a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists to conduct a study using the sea lamprey (a jawless vertebrate fish) that will work to discover how buildup of the protein alpha-synuclein affects synapses — the contacts between brain cells. The findings could lead to new targets for Parkinson’s medications.

“This research will provide insights into the earliest features of PD,” Dr. Roman-Vendrell said. “It has the potential for identifying treatments that can improve synaptic function. This will help in the development of therapies to slow or halt PD progression.”

Parkinson’s is characterized by the misfolding of a protein called alpha-synuclein, which causes the protein to form deposits (or “build-up”) in the brain. In addition to limiting the brain’s ability to produce dopamine, this abnormal build-up of alpha-synuclein at synapses is linked to thinking changes and dementia in PD. This build-up appears to occur early in the disease — before other signs of nerve cell degeneration.

About Alpha-Synuclein: When it comes to Parkinson’s disease, the protein called alpha-synuclein plays a key role. This protein begins to form sticky clumps in neurons (cells in the brain) in people with PD. Over time, the clumping kills healthy neurons and impairs the brain’s ability to produce dopamine, leading to Parkinson’s symptoms and ultimately a diagnosis.

This makes synapses an excellent target for treatment. However, not much is known about how alpha synuclein builds up at synapses. This slows down research and the ability for scientists to develop new treatment strategies.

Dr. Roman-Vendrell will inject PD-derived alpha-synuclein into the synapses of lampreys to see how it leads to synaptic dysfunction. Lampreys have large, visible neurons, making them used a lot in neuroscience research. Due to their large reticulospinal neurons, researchers can microinject antibodies and proteins to disrupt specific molecular targets at synapses. “We can then use high-resolution imaging [see image] for detailed analyses of synaptic structure and function,” Dr. Roman-Vendrell said.

For more than 10 years, the Marine Biological Laboratory has been levering the unique features of the sea lamprey's giant synapses and implementing them as a model for studying how alpha-synuclein impacts synapse structure and function. “To our knowledge, our lab is the first to utilize the lamprey synapse model to investigate impacts of PD on synapses,” said Dr. Roman-Vendrell.

“Our lampreys come from the Great Lakes, where they are an invasive species,” she said. “Scientists use them as models for neuroscience and developmental biology, as well as evolutionary biology and ecology.”

Dr. Roman-Vendrell will also investigate whether selected alpha-synuclein inhibitors can improve synapse function in PD. Of her Parkinson’s Foundation grant award, she said, “Many years ago, a dear family friend was diagnosed with Parkinson’s disease. It was heartbreaking to see her deteriorate and unable to do even basic things on her own. As a scientist, I was motivated to pursue neuroscience research that may help us find treatments for this terrible disease. It is a great honor to receive this award and to know that people with PD may benefit from the outcomes of my research.”

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

2022 Stanley Fahn Junior Faculty Award  

Improving Deep Brain Stimulation to Improve Motor Symptoms in Parkinson’s

Coralie de Hemptinne, PhD, of the University of Florida, a Parkinson’s Foundation Center of Excellence, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to study a way to improve deep brain stimulation (DBS) therapy for Parkinson’s disease (PD). She aims to develop a process that would automatically program DBS devices.

With DBS, a surgically implanted device delivers electrical pulses to brain structures involved in movement. DBS can be an effective treatment for movement symptoms in people with Parkinson’s.

It is challenging and time-consuming to customize a DBS device for each person. Though current technology makes it possible to program the device to avoid side effects, this is complex given the nearly infinite number of possible ways to program the device.

Automated methods to program the device are needed. This will reduce the complexity and improve the efficiency and effectiveness of DBS, allowing for more long-term benefits. One approach is to develop an algorithm, or set of rules, that automatically identify the best way to program the device. The rules would be based on signals of brain activity affected by DBS.

“Developing these algorithms could increase the effectiveness of DBS and improve the ease of treatment. It will remove the ‘trial and error’ process of doctor-managed stimulator changes. It could ultimately improve the quality of life for patients with Parkinson’s disease.” - Dr. de Hemptinne.

Dr. de Hemptinne will enroll 40 people with Parkinson’s undergoing implantation of DBS to treat their movement symptoms. The range and frequency of the stimulation will be varied to study their effects on brain signals. Based on the findings, she will develop an algorithm that automatically chooses these factors. Electrical signals in the brains of study participants will be recorded both during DBS implantation surgery and in-clinic. This will allow Dr. de Hemptinne to determine whether the algorithm is effective in choosing DBS settings.

Of her Parkinson’s Foundation grant award, she said, “Receiving this award is a great honor for me. It is especially meaningful to get this grant as a new independent principal investigator. It will allow me to develop my research projects and contribute to building my laboratory. It will also foster stronger collaborations with my colleagues. This award will be a launching point for my career to get bigger awards and grants and establish my research program.”

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

2025 Impact Award 

Highlighting Alpha-synuclein Clumps in PD with Small Molecule Trackers 

Tracking Parkinson’s disease (PD) progression is challenging. Doctors currently rely mostly on how a person’s symptoms change over time. Because those symptoms vary from person to person and can fluctuate from day to day, this approach can make it difficult to evaluate whether treatments are truly helping. 

For other brain diseases like Alzheimer’s, scientists have developed small molecules that can attach to disease-related protein clumps and make them visible on brain scans such as PET (positron emission tomography). These imaging tools allow researchers and clinicians to see where harmful proteins are building up in the brain, providing a clearer, more objective way to track disease progression and test therapies. 

Sarah Shahmoradian, PhD, recipient of a Parkinson’s Foundation Impact Award, is exploring whether a similar biomarker tag could work for Parkinson’s. Working with collaborators at Massachusetts General Hospital, a Parkinson’s Foundation Center of Excellence, Dr. Shahmoradian is studying a specially designed small molecule that appears to bind strongly and selectively to misfolded alpha-synuclein clumps—the abnormal protein deposits that are a hallmark of Parkinson’s disease. 

“We aim to provide the first atomic-resolution view of how a promising small-molecule PET tracer binds to alpha-synuclein fibrils in human Parkinson’s brain,” says Dr. Shahmoradian. 

Inside the brain, misfolded alpha-synuclein proteins can form dense clusters that disrupt how nerve cells work. Evidence suggests these toxic protein forms may even spread from one neuron to another, contributing to the gradual worsening of symptoms in PD. A molecule that can label these alpha-synuclein clumps could allow researchers and physicians to visualize Parkinson’s pathology directly in the living brain—an advance that could transform diagnosis, treatment monitoring and research. 

From her lab at the University of Texas Southwestern Medical Center in Dallas, Dr. Shahmoradian will use high-resolution imaging methods — developed through her earlier Parkinson's Foundation-supported research— to see precisely how this new molecule attaches to alpha-synuclein fibrils. Understanding this interaction at the molecular level will help scientists fine-tune the tracer for future clinical imaging. 

The next step is to adapt the molecule so it glows under the microscope. By applying it to neurons grown in the lab that model Parkinson’s disease, or to slices of PD brain tissue, Dr. Shahmoradian and her team hope to track where alpha-synuclein clumps appear and how they move inside cells. If successful, this work will demonstrate that the molecule can serve as a powerful diagnostic and research tool for Parkinson’s. 

“This award gives me the opportunity to pursue a line of research I see as essential for advancing how we detect and monitor Parkinson’s disease,” said Dr. Shahmoradian. “This research will help accelerate the development of clinically useful biomarkers for early diagnosis and therapeutic monitoring in PD.” 

2022 Stanley Fahn Junior Faculty Award  

Learning About Early-Stage Accumulation of Alpha-Synuclein in the Parkinson’s Brain

Sarah Shahmoradian, PhD, of the University of Texas Southwestern Medical Center, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to study early-stage build-up of a protein called alpha-synuclein in the brain.

“Results from these studies will fundamentally advance our understanding of how Parkinson’s disease develops,” Dr. Shahmoradian said. “They could thereby inform on novel therapeutic strategies.”

Parkinson’s disease (PD) is characterized by the misfolding of the alpha-synuclein protein into an abnormal shape. These shapes clump together to form sticky deposits in the brain that disrupt the brain’s ability to produce dopamine — and are connected to cognitive decline and dementia. This build-up appears to occur early in the disease.

About Alpha-Synuclein: When it comes to Parkinson’s disease, the protein called alpha-synuclein plays a key role. This protein begins to form sticky clumps in neurons (cells in the brain) in people with PD. Over time, the clumping kills healthy neurons and impairs the brain’s ability to produce dopamine, leading to Parkinson’s symptoms and ultimately a diagnosis.

Prior research has largely focused on the late stages of alpha-synuclein deposits. However, much is still not known about the critical early events that cause a single abnormal alpha-synuclein molecule to recruit and transform additional molecules to becoming toxic. This leads to build-up and spreading to other brain cells.

Ongoing research is focused on where alpha-synuclein first begins to accumulate in the brain. Previous studies have used high-resolution imaging to analyze alpha-synuclein that is either chemically extracted from the human brain or artificially produced. However, researchers still do not know if the molecular structure of the toxic form of alpha-synuclein can be found in a natural state within brain cells.

Dr. Shahmoradian will apply state-of-the-art, high-resolution imaging techniques to uncover the molecular structure of alpha-synuclein within the brain cells, and to study how alpha-synuclein contributes to the disease process in Parkinson’s. This research will define where and how alpha-synuclein buildup first occurs within human brain cells.

Of her Parkinson’s Foundation award, she said, “Being granted this generous support from the Parkinson’s Foundation cements my commitment to continue research in Parkinson's disease. Through receiving this award from an organization intimately linked to those affected by PD, I feel a heightened sense of personal responsibility and urgency in executing my research.”

2022 Stanley Fahn Junior Faculty Award  

Targeting the PARP1 Enzyme to Halt Parkinson’s Progression

Tae-In Kam, PhD, of Johns Hopkins University School of Medicine, a Parkinson’s Foundation Center of Excellence, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to study the role of an enzyme called PARP1 in Parkinson’s disease (PD). An enzyme is usually a protein that alters how brain cells communicate. The goal is to halt the progression of Parkinson’s through exploring different mechanisms that target this enzyme.

The brain chemical dopamine is responsible for smooth, controlled movements. When the brain cells that produce dopamine die at a fast pace, early Parkinson’s movement symptoms occur — including rigidity and balance issues. All people with Parkinson’s have a low level of dopamine. Currently there are no treatments that prevent the progression of the disease.

A protein called alpha-synuclein is involved in the loss of dopamine brain cells. In Parkinson’s, alpha-synuclein misfolds and forms deposits in the brain. These deposits disrupt the brain’s normal functioning in people with PD. How exactly this protein causes Parkinson’s to progress is still unknown.

Dr. Kam recently found that in Parkinson’s, alpha-synuclein activates an enzyme called PARP1. Essentially, the enzyme sends toxic signals to brain cells, leading to cell death. How this occurs is not known.

In a mouse model, Dr. Kam will study PARP1’s role in the development of Parkinson’s, looking to identify compounds that affect the enzyme’s role in damaging nerve cells in Parkinson’s. These compounds could be a new target for future PD treatments.

“Our long-term goal is to discover treatments that impact PARP1, as well as discovering biomarkers to help diagnose PD,” Dr. Kam said. “This approach should have a significant impact on slowing or halting the degenerative process of PD and related diseases.”

Of his Parkinson’s Foundation grant award, he said, “This award will enable us to open new research horizons.”

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

2021 Postdoctoral Fellowship
2022 Launch Award

Understanding the Blood-Brain Barrier’s Role in Parkinson’s Disease

Aurélie de Rus Jacquet, PhD, of CHU de Québec-Université Laval, received a Parkinson’s Foundation Launch Award to study molecules (or cells) that can affect the blood-brain barrier and thus contribute to Parkinson’s disease (PD).

“The Launch Award will enable me to investigate the role of the blood-brain barrier and brain-blood communication in the onset and development of Parkinson’s,” said Dr. de Rus Jacquet. “We hope to identify factors on either side of the blood-brain barrier that interfere with its proper functioning in Parkinson’s. These factors could become drug targets.”

In the brain and body, Parkinson’s disease:

• Decreases the rate of certain brain cells.
• Causes an increase in inflammatory signals in the bloodstream.
• Makes PD-related protein called alpha-synuclein more toxic in the brain.
• Increases production of antibodies that recognize alpha-synuclein.

Cells in the brain are protected by a specialized security system called the blood-brain barrier. This is a network of blood vessels that allows the entry of essential nutrients while blocking other substances. People with Parkinson’s disease progressively lose this protection. When this happens, toxins and immune cells from outside the brain can enter the brain and speed disease progression. Researchers do not know what causes this. Loss of the barrier’s protection could be induced by toxic signals in the blood. It also could be caused by an inability of brain cells to maintain a strong barrier.

In her research, Dr. de Rus Jacquet will use complex state-of-the-art Parkinson’s models. She established a 3-D model of the blood-brain barrier using cells generated from both people with and without a PD-related gene mutation.

"Opening a new laboratory as an early career scientist will be an exciting adventure. I will face many challenges. but this Parkinson’s Foundation grant will greatly facilitate my success."

She will focus on brain cells called astrocytes, which are essential for the blood-brain barrier to efficiently function. She has found that Parkinson’s astrocytes are not able to form a strong barrier. Dr. de Rus Jacquet will test whether this leads to immune cells infiltrating the brain side of her model, mimicking a key aspect of Parkinson’s.

In a second set of experiments, Dr. de Rus Jacquet will study how plasma proteins are involved in Parkinson’s. She will expose the “blood” side of the barrier to the plasma of donors with and without Parkinson’s. She will determine how this plasma affects barrier function. She will see which plasma proteins cross the blood-brain barrier to affect cell health.

Of her Parkinson’s Foundation grant award, Dr. de Rus Jacquet said, “The Launch Award will have a profound impact on my career and abilities to continue research on Parkinson’s disease. This award is a recognition of research excellence. It also financially supports the first two years of my future independent career. Opening a new laboratory as an early career scientist will be an exciting adventure. I will face many challenges. but this Parkinson’s Foundation grant will greatly facilitate my success.”

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

Explore more of Dr. de Rus Jacquet’s research

Aurelie de Rus Jacquet will be furthering her research for which she received a Parkinson’s Foundation research grant in 2021. Read about her Postdoctoral Fellowship for Basic Scientists research below.

What Role Does the Blood-Brain Barrier Play in Parkinson’s?

Postdoctoral Fellowship for Basic Scientists

Aurelie de Rus Jacquet, PhD of Université Laval, Québec (Canada), received a Parkinson’s Foundation Postdoctoral Fellowship grant to study molecules (or cells) that could promote dysfunction in a specialized vascular system called the blood-brain barrier. People with Parkinson’s disease progressively lose the blood-brain barrier’s protection, but it is not currently understood why.

This barrier controls the crossing between the blood and the brain, and prevents toxic molecules found in the blood from entering the sensitive brain tissue and damaging cells.

The goal of this research is to identify factors on either side of the blood-brain barrier that could become targets for new drug treatments for PD.

“Most of the past research in the field has focused on understanding why neurons die over the course of the disease, but it is becoming clear that Parkinson’s disease is more complex than the loss of neurons,” said Dr. de Rus Jacquet. “Non-neuronal cells are also involved, and they could hold the key to understanding the global events underlying Parkinson’s disease onset and progression.”

Dr. de Rus Jacquet continued, “The second objective of the research is to understand if the blood of people with Parkinson’s disease contains toxic molecules that enter the brain and induce a loss of neurons and inflammation of the brain tissue. This topic is relatively less studied, but I find it fascinating because it could help identify new drug targets to slow or stop disease progression.”

Dr. de Rus Jacquet has established a 3D model of the blood-brain barrier using cells generated from healthy donors or people with a specific Parkinson’s disease-related gene mutation. She hopes to discover if non-neuronal cells or blood-borne factors may be responsible for the loss of neurons, and if targeting these cells could possibly help combat neurodegeneration.

“This award is an important recognition that my work can have a meaningful impact on the lives of people with Parkinson’s,” said Dr. de Rus Jacquet. “I would like to thank all Parkinson’s Foundation supporters for helping us move the research forward. Finding a cure for Parkinson’s disease and improving people’s lives is at the heart of what we do, and we can only achieve these goals by working together.”

2022 Postdoctoral Fellowship 

Targeting A Protein Involved in Dopamine Regulation Could Improve Effectiveness of Levodopa

Meghan Bucher, PhD, of Columbia University Medical Center, a Parkinson’s Foundation Center of Excellence, received a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists to identify compounds that treat the movement symptoms of Parkinson’s disease (PD), either alone or in combination with levodopa. The goal is to improve the effectiveness of PD treatment.

There is no cure for Parkinson’s disease or treatment that slows the progression of the disease. PD treatments are tailored to every person’s individual symptoms. Treatment options can be a combination of physical therapy, exercise, medication and others. Levodopa is the go-to PD medication that treats movement symptoms, but may become less effective over time. As a result, new approaches to treat Parkinson’s disease are desperately needed.

The brain chemical dopamine is responsible for smooth, controlled movements. When the brain cells that produce dopamine die at a fast pace, the movement symptoms of Parkinson’s begin to occur — including rigidity and balance issues. A protein called synaptic vesicle glycoprotein 2C (SV2C) helps the brain regulate dopamine transmission. Its expression is enriched in the areas of the brain affected by PD.

In previous studies, SV2C has been identified as a risk factor for developing PD. It has also been found to affect how people with Parkinson’s respond to symptom relief from levodopa.

“My goal is to develop and screen novel compounds that will target SV2C activity,” said Dr. Bucher. “This research will determine their benefits in treating people with Parkinson’s.”

Dr. Bucher will investigate whether SV2C is a target for treatment that could alleviate movement symptoms and halt or slow disease progression. She will also evaluate whether a treatment targeting the protein could improve the effectiveness of levodopa when it comes to minimizing PD symptoms.

She has developed a lab test to evaluate compounds that could regulate SV2C activity. She will then use several Parkinson’s models to evaluate the compounds’ effect on dopamine transmission.

Of her Parkinson’s Foundation grant award, Dr. Bucher said, “The support of the Parkinson's Foundation will facilitate my transition into an independent investigator. It will allow me to continue my intellectual pursuit researching both the causes of and treatments for Parkinson's disease.”

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