2025 Grand Challenges in Parkinson's Disease

Dario obtained a B.Sc. (1988) and Ph.D. (1991) from the University of Birmingham (UK). He carried out postdoctoral at the University of Dundee from (1991-1997), where he became fascinated by how all aspects of cell biology and human diseases are influenced by a class of enzyme called “kinases.” In 1997, Dario became a program leader at the Dundee MRC Unit and was appointed as its director in 2012. His current research focuses on understanding the roles of the LRRK2 pathway in Parkinson’s and how knowledge of this research can be exploited to develop new ways to diagnose and slow the progression of this disease. Dario is passionate about mentorship, open science, sharing, working with industry and clinicians, as well as fostering a collaborative culture. Dario currently serves as President of the International Union of Biochemistry and Molecular Biology (IUBMB).

Veerle Baekelandt, Ph.D., is a neurobiologist and full professor at the faculty of medicine of the KU Leuven, Belgium. She heads the Laboratory for Neurobiology and Gene Therapy. The general interest of the lab concerns the molecular pathogenesis of Parkinson’s disease and related disorders. The approach consists of generating novel cellular and rodent models based on genes involved in familial forms of Parkinson’s disease, with the aim to better understand the pathogenesis of the disease. The final goal is to develop novel causal therapeutic strategies that can cure or slow down the disease. The lab is using viral vector technology, stereotactic neurosurgery and non-invasive molecular imaging as core technologies. Her current research focuses on the role of α-synuclein aggregation in Parkinson’s disease and multiple system atrophy, and on the function of LRRK2, a kinase linked to Parkinson’s disease. In the context of the ASAP international collaborative research network project IMPACT-PD, she is also focusing on the P-type ATPases ATP13A2 (PARK9) and ATP10B, two transporters that are genetically implicated in PD. Dr. Baekelandt is recognized internationally for the application of viral vectors in rodent brain to model and study Parkinson’s disease. She has also contributed to groundbreaking research demonstrating a prion-like behavior of the α-synuclein protein.

Dr. Jacqueline Burré is an associate professor of Neuroscience at the Helen and Robert Appel Alzheimer’s Disease Institute and the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine, and co-director of the Graduate Program in Neuroscience. She obtained her doctorate degree in biochemistry from Goethe University in Germany, where she studied the composition of synaptic vesicles. As a postdoctoral fellow at UT Southwestern Medical Center and then Stanford University, Dr. Burré pursued her interests in neuronal communication with Nobel laureate Thomas Südhof, focusing on the role of α-synuclein in normal brain function and in Parkinson’s disease. In her own laboratory, she continues the studies of synucleins and has expanded her focus on SNAREopathies. Her lab applies biophysics, biochemistry, cell biology, electrophysiology, and imaging in cultured cells, C. elegans, yeast, and mouse models of neuropathology, with the goal to understand disease mechanisms at a molecular level, and to use this knowledge as a basis for designing therapeutic strategies. Based on findings in her lab, two pilot clinical trials are currently on-going, testing the efficacy of 4-phenylbutyrate in children with STXBP1 mutations and testing the hypothesis of altered membrane binding of α-synuclein as an early biomarker for synucleinopathies.

Dr. Sreeganga Chandra is a Professor in the Departments of Neurology and Neuroscience. Dr. Chandra’s laboratory explores two inter-related themes — synapse maintenance and neurodegeneration. Her lab investigates Parkinson’s disease genes and risk alleles that encode synaptic proteins and how they impact synaptic function and neuronal health. Her lab has advanced our understanding of how synaptic vesicle deficits cause Parkinson’s disease. She also investigates the mechanisms of neuronal ceroid lipofuscinoses (NCL) and their impact on presynaptic properties. The long-term goal of her research is to parlay basic understanding of Parkinson’s disease and NCL genes for the development of early disease modifying therapies. Dr. Chandra is deeply vested in training the next generation of scientists investigating neurodegeneration.

Dr. De Camilli earned his M.D. from the University of Milano (Italy) and was a postdoctoral fellow at Yale. After a brief return to Italy, he moved back to Yale in 1988 where he is Professor of Cell Biology and of Neuroscience at the School of Medicine. At Yale, he served as Chair of the Department of Cell Biology, of the Department of Neuroscience, as Director of the Kavli Institute for Neuroscience and in 2005 co-founded the Yale Program in Cellular Neuroscience, Neurodegeneration and Repair. Since 1992, he has been a Howard Hughes Medical Institute Investigator. He is member of the National Academy of Sciences (USA), the National Academy of Medicine (USA) and the American Academy of Arts and Sciences.

De Camilli’s lab investigates mechanisms underlying the dynamics of cellular membranes, with emphasis on the role of these mechanisms in the brain function in physiology and disease, including Parkinson’s disease. His studies on synaptic vesicle recycling and on the role of phosphoinositides in control of endocytosis had broad implications in the fields of membrane traffic and phospholipid signaling. More recently, he helped advance the field of organelles cross-talk at membrane contact sites.

Dr. Matt Farrer is a Parkinson’s disease biologist, formerly trained in biochemistry, molecular and statistical genetics at King’s and Imperial College London. He subsequently did fellowships in medical genetics and neurogenetics. He became an Assistant and then full Professor while at Mayo Clinic, where he became a Distinguished Investigator in 2008. He relocated to Vancouver for a Canada Excellence Research Chair in 2010, and subsequently moved to the McKnight Brain Institute at the University of Florida in 2019. Over this ~25 year span, Dr. Farrer’s team has been responsible for the genetic-linkage of all causal genes for late-onset dominantly-inherited Parkinson’s disease, and which cannot be distinguished clinically from the idiopathic condition. These discoveries confer the highest genotypic and population risk, globally, and include SNCA multiplications, LRRK2 p.G2019S, VPS35 p.D620N, RME-8 p.N855S and, most recently, RAB32 p.S71R. His group has also contributed to the creation and biological characterization of “physiologic” mouse models, based on that gene dysfunction. His view of the disease is from its evolutionary past, encompassing its population prevalence and penetrance, and its molecular etiology. His current focus is on immune biology, dopamine circuitry and pathophysiology, and in targeting therapeutic development to halt disease.

Matthew Fell is currently an Executive Director in Neuroscience discovery at Merck Research Laboratories. In his current role, Matt is responsible for leading a team of scientists focused on the discovery of neuroimmune based therapies for neurodegenerative diseases. At Merck, Matt has co-led teams that have discovered and advanced multiple molecules into clinical trials for Alzheimer’s disease, amyotrophic lateral sclerosis and Parkinson’s disease including MK-1468 (a LRRK2 kinase inhibitor). Matt received his B.Sc. in Biomedical Sciences/Pharmacology and a Ph.D. in Neuropsychopharmacology from the University of Bradford, UK. As a postdoctoral fellow in the Psychiatric Disorders team at Eli Lilly and Company, Matt’s research focused on the therapeutic potential of group II metabotropic glutamate receptors in schizophrenia. Following his postdoctoral fellowship, Matt joined the Merck Neuroscience Discovery group at Merck Research Labs, New Jersey in 2011 but relocated to Boston in 2014 to help establish the Neuroscience Discovery group at Merck Research Labs in Boston.

Dr. Harper is the Bert and Natalie Vallee Professor of Molecular Pathology and the Chair of the Department of Cell Biology at Harvard Medical School. His work focuses on mechanisms underlying organelle quality control by the ubiquitin system and autophagy. His work has led to the discovery of a phosphorylation-driven feed-forward ubiquitylation pathway controlling PARKIN-dependent mitophagy, and a molecular understanding of the pathways controlling selective autophagy. Dr. Harper has employed interaction proteomics to define interactions and complex biological pathways linked with diseases. Awards include the Javits Neuroscience award, as well as election to the American Academy of Arts and Sciences and to the National Academy of Sciences.

Anastasia (Stacy) Henry is a Senior Director and Staff Scientist at Denali Therapeutics, where she leads a team within the Pathway Biology group. Her research focuses on understanding how lysosomal dysfunction and disrupted neuronal homeostasis contribute to Parkinson’s disease and other neurodegenerative disorders. Specifically, her group has been investigating the mechanisms by which disease-associated proteins affect lysosomal function and translating this insight into biomarker identification and interpretation, enabling the development of novel therapeutic approaches to treat Parkinson’s disease and neuronopathic lysosomal storage disorders. Stacy has served as the project leader for Denali’s DNL310 program, a blood-brain-barrier-penetrant enzyme replacement therapy for MPS II disease, and leads the biology efforts supporting the LRRK2 kinase inhibitor program, both of which are now in late-stage clinical studies. She earned her Ph.D. from the University of California, San Francisco, under the mentorship of Mark von Zastrow, and completed her postdoctoral training in the Neuroscience Department at Pfizer in Warren Hirst’s lab.

Dr. Darren Moore received an undergraduate degree from the University of East Anglia in 1998 and a Ph.D. in molecular neuroscience from the University of Cambridge in 2001 in the laboratory of Dr. Piers Emson. He conducted postdoctoral training with Professor Ted Dawson in the Department of Neurology and Morris K. Udall Parkinson’s Disease Research Center of Excellence at the Johns Hopkins University School of Medicine in Baltimore. Dr. Moore joined the faculty at Johns Hopkins in 2005 as an instructor and became assistant professor in 2006. In 2008, Dr. Moore moved to the Swiss Federal Institute of Technology (EPFL) in Lausanne as an assistant professor in the Brain Mind Institute. In 2014, Dr. Moore joined the faculty at VAI as an associate professor in neurodegenerative science. He subsequently was promoted to professor in 2017 and to chair of the Department of Neurodegenerative Science in 2020. His laboratory is interested in understanding the biology and pathophysiology of gene products associated with inherited Parkinson’s disease.

Dr. Simon earned M.D. and Ph.D. degrees from Washington University in St. Louis in 1993 and completed the Harvard-Longwood Neurology Residency in Boston, followed by a Movement Disorders Fellowship at Massachusetts General Hospital. He is now Professor of Neurology at Harvard Medical School and Chief of the Division of Movement Disorders at Beth Israel Deaconess Medical Center (BIDMC), as well as Director of the Parkinson’s Foundation Center of Excellence at BIDMC. Dr. Simon is involved in clinical studies as well as laboratory research to test strategies for potential neuroprotective effects in Parkinson’s.  His laboratory research focuses on the roles of mitochondrial dysfunction, the retromer complex and alpha-synuclein toxicity.  Dr. Simon has served on the Steering Committees for multiple clinical studies. He also has served terms as Chair of the Scientific Review Committee of the Parkinson’s Study Group (PSG) and as an elected member of the PSG Executive Committee. He previously served as a member of the NIH Molecular Neurogenetics study section and serves on the NINDS Biospecimen Review Access Committee (PD-BRAC). He is now Chair of the Cure Parkinson’s international Linked Clinical Trials Committee and Chair of the Scientific Advisory Board for the Weston Brain Institute.

The Volpicelli-Daley Lab is interested in how formation of α-synuclein inclusions impact synapse structure and function. In addition, the lab is also interested in how mutations in GBA1 and changes in lipid metabolism cause neuronal dysfunction. Working with industry, the lab is testing pharmacologic compounds to prevent GBA1 mutant associated defects. Dr. Volpicelli-Daley teaches approaches in basic science to first year MSTP students and co-directs a graduate Neuroanatomy course. She has received mentoring awards over the years.

Dr. West serves as the director of the Duke Center for Neurodegeneration and Neurotherapeutics, established in 2018, and runs a multidisciplinary laboratory focused on mechanisms and risks in neurodegeneration diseases, novel biomarkers, and therapeutic approaches for disease modification strategies. Dr. West is a founding member of the NINDS Parkinson Disease Biomarker Program (PDBP) steering committee, a past member of the Executive Scientific Advisory Board at the Michael J. Fox Foundation (MJFF), an advocate for open-science policy, and a board-reviewing editor for neurodegeneration research at the HHMI-backed journal eLife. Dr. West has published more than a hundred manuscripts and has served as the lead PI for several successful large multidisciplinary research teams including an MJFF-supported LEAPs team to develop LRRK2-targeted therapeutics, an NINDS-backed R33 and U01 program projects to develop α-synuclein and LRRK2-related assays, and have recently participated as a project PI in a Udall Center of Excellence in Parkinson’s disease research, with work focusing on inflammation, as well as PI on an Aligning Science Across Parkinson’s (ASAP) research team focused on the gut-brain axis in α-synucleinopathies.

Dr. Darren Moore seeks new diagnostic and treatment approaches for Parkinson’s by investigating the inherited form of the disease, which comprises 5% to 10% of cases. He aims to translate the understanding of these genetic mutations into better treatments and new diagnostic tools for Parkinson’s, both inherited and non-inherited. Discoveries from Dr. Moore’s lab routinely elucidate the faulty molecular interactions that transform healthy, functioning neurons into diseased ones.

Dr. Melissa Hoyer studies the fundamental cellular processes that support brain health. To date, her research has revealed important insights into several critical cellular systems required for normal function — and detailed how errors in these vital processes contribute to disease.