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“I hope that this might lead to the development of targeted genetic therapies for PD.”
James Dahlman, Ph.D.

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2016 Investigator-Initiated Projects

PDF is funding several innovative investigator-initiated research projects in 2016. Read summaries of these projects below.

Stanley Fahn Junior Faculty Awards

[+] Role of Direct Pathway Striatal Activity in Dyskinesia

Alexandra Nelson M.D., Ph.D., University of California, San Francisco

The gold standard treatment for Parkinson’s movement symptoms is levodopa, often prescribed as Sinemet®. But after taking this medicine for several years, many people develop troublesome involuntary movements called dyskinesias. In studies with laboratory mice engineered to have Parkinson’s symptoms, we will investigate how levodopa changes brain activity to both improve movement and to cause dyskinesias. Using a technique called optogenetics, we will monitor the activity of two types of cells in a critical brain area called the striatum, both before and after levodopa treatment. Then we will compare the responses. We believe that the activity of one type of cells may closely mirror the beneficial responses to levodopa, while the other may closely mirror the disabling, dyskinetic responses. A better understanding of these two groups of cells will help in the development of Parkinson’s therapies that provide the benefits of levodopa while minimizing the side effects.


[+] Parkinson’s Disease Genetic Risk Factors in Latino Populations

Ignacio Fernandez Mata, Ph.D., University of Washington

In recent years, dozens of genetic mutations have been identified that either cause Parkinson’s directly or increase a person’s susceptibility to developing the disease. All of these genes have been discovered in populations of European or Asian ancestry. Little is known about their role in Latinos, who carry a mixture of genes from indigenous Americans, Europeans and Africans. In earlier studies we have identified 2,000 people with PD in six South American countries and matched them with 2,000 healthy controls. Our study will genetically screen blood samples from these individuals to identify new susceptibility genes in Latinos. In families with many members affected, we will also sequence all known genes that cause PD in order to identify new genetic variants that cause PD. These data will be crucial in understanding the role of genetics in Latinos with PD, and will allow Latinos to participate in clinical trials for potential treatments targeted toward individuals with specific genetic variants.


[+] High Throughput In Vivo Screens for Targeted PD Gene Therapies

James Dahlman Ph.D., Georgia Institute of Technology

DNA and RNA therapies are a promising new approach to gene therapy for Parkinson’s. But, as with all therapies taken by mouth, researchers need to overcome the difficulties of getting these drugs through the digestive system and past the blood-brain barrier to the specific brain cells where they are needed. One way to do this is to encase the DNA or RNA therapy inside a protective chemical structure called a nanoparticle. Nanoparticles, like other investigational treatments, must be tested in laboratory animals. To date, the expense of these experiments has greatly limited the number of nanoparticles that could be studied. Using a cutting-edge system that our team has designed, we will be able to test 10,000 nanoparticles in mice to find the ones that are best at delivering DNA and RNA therapies to the brain cells affected by PD. Our results will help us synthesize a second generation of nanoparticles that are even more effective.


Research Fellowships

[+] Dynamic Interaction Between Striatal Dopaminergic and Cholinergic System in Regulation of Beta-band Oscillations as Mechanisms Underlying Pathophysiology of Parkinson’s Disease

Daigo Homma, Ph.D., Mentor: Ann Graybiel, Ph.D., Massachusetts Institute of Technology

[+] Loss of Glucocerebrosidase Increases Dopaminergic Neuronal Vulnerability by Impairing Autophagic Flux

Emily Rocha, Ph.D., Mentor: J. Timothy Greenamyre, M.D., Ph.D., University of Pittsburgh Medical Center

[+] Investigating the Function of Mitochondrial-Derived Vesicles in Neurons and Their Role in Parkinson’s Disease

Rosalind Roberts B.Sc., D.Phil., Mentor: Edward Fon, M.D., McGill University

[+] Alpha-Synuclein Mediated Toxicity in the Aged Rat Brain: Molecular Mechanisms in the Nucleus

Ivette Sandoval, Ph.D., Michigan State University, Mentor: Timothy Collier, Ph.D., Michigan State University

[+] Thalamostriatal Adaptations in Parkinson’s Disease

Asami Tanimura, Ph.D., Mentor: D. James Surmeier, Ph.D., Northwestern University

PDF-APDA Summer Student Fellowships

[+] Identifying Elements of the Transcriptional Regulatory Network of PARIS (ZNF746) Involved in α-Synuclein-Induced Neurodegeneration

Preston Ge, Mentor: Ted Dawson, M.D., Ph.D., Johns Hopkins University

[+] The Interaction of Parkinson’s Disease Gene FBXO7 with Bag2

Dima Hage, Mentor: David Park, Ph.D., University of Ottawa

[+] DBH-ASYN Mouse Model, Effect of Inflammation in Gastrointestinal System

Kiana Khosravian, Mentor: Malú Tansey, Ph.D., Emory University

[+] The Role of the ESCRT Complex in a Vesicular Trafficking Pathway from Mitochondria to Lysosomes

Sydney Lee, Mentor: Edward Fon, M.D., McGill University

[+] REM Sleep Without Atonia Signatures Help Distinguish Between Synucleinopathy Disorders

Stuart McCarter, Mentor: Erik St. Louis, M.D., Mayo Clinic

[+] In Vivo Optical Measurement of Direct and Indirect Path Projection Neuron Activity in a Parkinson’s Disease Rodent Model with Treatment of L-DOPA and Cannabinoid Antagonists

Rachel Mikofsky, Mentor: David Sulzer, Ph.D., Columbia University

[+] Relevance of Amino Acid Charge/Polarity in New Familial Mutants of Alpha-synuclein

Emily Ong, Mentor: Shubhik DebBurman, Ph.D., Lake Forest College

[+] Impact of Inflammation on Alpha-Synuclein Expression in the Colonic Enteric Nervous System

Henry Resnikoff, Mentor: Marina Emborg, M.D., Ph.D., University of Wisconsin-Madison

[+] Association Between Water Source and Incident Parkinson Disease

Maya Silver, Mentor: Brad Racette, M.D., Washington University

[+] Investigation of Dopamine Neuron Degeneration as a Consequence of Microbiome-Derived Bacteria

Samuel Stanley, Mentor: Kim Caldwell, Ph.D., University of Alabama

[+] Parkinson’s Disease Penetrance in Obligate Carriers of SMPD1 Mutations

Adina Wise, Mentor: Roy Alcalay, M.D., M.Sc., Columbia University Medical Center

[+] High Angular Resolution Diffusion Imaging Correlates of Cognitive Impairment in Parkinson’s Disease

Kali Xu, Mentor: Kathleen Poston, M.D., M.S., Stanford University

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