2023 Grand Challenges in Parkinson’s Disease

Nicole Calakos, M.D., Ph.D., is a physician-scientist who cares for patients with movement disorders and maintains an active laboratory research program. Dr. Calakos is the Lincoln Financial Group Professor of Neurology and Neurobiology and Chief of the Movement Disorders section in Neurology at Duke University Medical Center. Her laboratory studies how synaptic plasticity generates learning and adaptive behavior; and how its disruption causes diseases of the basal ganglia circuitry. The Calakos Lab is widely recognized for its contributions to understanding habit formation, compulsive behavior and dystonia and for the generation of new methodologies to study basal ganglia physiology.

Dr. Calakos received her bachelor’s degree from the University of California at Berkeley, her M.D. and Ph.D. degrees from Stanford University, and residency training in neurology at the University of California at San Francisco.

Dr. Calakos’ contributions have been recognized through a number of awards, leadership and service opportunities. She is a member of the National Academy of Medicine, fellow of the American Association for the Advancement of Sciences, and 2023 recipient of the ASCI Korsmeyer award. Dr. Calakos advocates for basic and translational neuroscience through these organizations and activities that have included: the Board of Directors for the American Neurological Association, governance committee for the Duke University Institute for Brain Sciences and scientific advisory boards for disease foundations.

Dr. Rui Chang received his B.S. in Biological Sciences and Biotechnology from Tsinghua University, China, in 2005. He then studied sensory transduction with Emily Liman and earned his Ph.D. in Neuroscience at the University of Southern California in 2011. He completed his postdoctoral training with Stephen Liberles at Harvard Medical School, where he investigated how body sensory cues are monitored by the brain through the vagus nerve, and how these internal signals regulate whole body physiology. He joined both the Department of Neuroscience and the Department of Cellular and Molecular Physiology at Yale University School of Medicine in January 2018. The Chang lab uses state-of-the-art molecular, genetic, and imaging approaches including single-cell gene expression profiling, virus-based anatomical mapping, in vivo imaging, optogenetics, and chemogenetics to reveal the physiological functions of diverse organ-to-brain circuits. The goal is to better understand the important body-brain interface, and to develop novel neuronal-based therapeutic strategies for disease intervention.

Dr. Hong-Yuan Chu received his Ph.D. in pharmacology from Shanghai Institute of Materia Medica. He then completed postdoctoral training at the National Institute of Mental Health and Northwestern University. In 2019, he joined Van Andel Institute’s Department of Neurodegenerative Science as an assistant professor. Dr. Chu serves as a reviewer for eLife, Journal Parkinson’s Disease, the Frontiers journals, and others. He is the recipients of several awards, including the prestigious 2020 BBRF Young Investigator award.

Anastasia (Stacy) Henry leads a team of scientists within the Pathway Biology group at Denali Therapeutics.  Her lab is focused on understanding the mechanisms by which disease-associated proteins affect lysosomal function and ultimately contribute to pathogenesis, enabling the development of novel therapeutic approaches to treat Parkinson’s disease and neuronopathic lysosomal storage disorders.  She leads biology efforts to support the LRRK2 kinase inhibitor programs at Denali and to explore the role of lysosomal function in neurodegeneration more broadly. Dr. Henry received her Ph.D. from the University of California, San Francisco in the lab of Mark von Zastrow and her postdoctoral training in the neuroscience department at Pfizer in the lab of Warren Hirst.

George W. Huntley received his B.A. in Physiology from UC San Diego and his Ph.D. in Neuroscience at UC Irvine working with Edward G. Jones on the structural and functional organization of motor representations in monkey motor cortex. His postdoctoral training with Dr. John Morrison focused on defining GluA subunit distribution at identified synapses in primate cerebral cortex. His early work in his own laboratory explored mechanisms of circuit plasticity of motor representations in motor cortex and the role of somatosensory experience in shaping development of motor representations, work for which he was awarded the Cajal Club’s “Cortical Explorer Prize.” Subsequent efforts focused on defining how the cadherin family of cell adhesion molecules and extracellular proteolysis proactively shape developing and mature circuits in health and disease. Recent efforts, with his long-time collaborator Deanna Benson, have focused on understanding the basis of early-appearing cognitive and psychiatric-like non-motor symptoms of Parkinson’s, interrogating mouse models behaviorally, anatomically, electrophysiologically and molecularly to infer how risk-gene mutations co-opt circuit structure and function. He is currently Professor of Neuroscience at Mount Sinai and directs the Neuroscience Ph.D. graduate training program.

Dr. Virginia M.-Y. Lee studied music at the Royal Academy of Music in London (1962-1964) and received her Ph.D. in Biochemistry from the University of California at San Francisco in 1973. She joined the Department of Pathology and Laboratory Medicine at the Perelman School of Medicine in 1981 and rose to become Professor of Pathology & Laboratory Medicine in 1989. Dr. Lee identified tau, alpha-synuclein and TDP-43 as disease proteins that form unique inclusions in Alzheimer’s, Parkinson’s and frontotemporal degeneration/Lou Gehrig’s disease, respectively, and has advanced understanding of their roles in these disorders. Dr. Lee’s h-index is 146 and she is listed among the 10 most highly cited AD researchers from 1985-2008 and among the top 400 most highly influential biomedical researchers from 1996-2011. She has been ranked 2 among Top Female Scientists for 2022 by Research.com. Dr. Lee is the recipient of many honors and awards including the Lifetime Achievement Award in Alzheimer’s Disease Research, Robert A. Pritzker Award for Leadership in Parkinson’s Disease Research from the Michael J. Fox Foundation, and the Breakthrough Prize in Life Sciences.

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.

A static cell is a dead cell. A broad interest in the Roy lab is to explore movement in neurons — mechanisms that convey, deposit and retain cargoes in axons, dendrites and synapses. A related interest is to manipulate trafficking-pathways for therapeutics in neurodegenerative diseases (particularly gene- and CRISPR- based therapies). Relevant to this meeting, the lab is interested in the physiologic role of alpha-synuclein at synapses, and early pathophysiologic transitions that ultimately lead to Parkinson’s disease and related disorders.

Dr. Sharma’s lab studies neurodegenerative diseases, using molecular-cellular techniques, patient-derived induced neurons, as well as mouse genetic models. He studied microbiology for his undergraduate degree. During his Ph.D. thesis with Dr. Gergely Lukacs, he trained as a molecular cell biologist, while studying misfolding and quality-control of the cystic fibrosis protein CFTR. He applied this training to neuroscience during his postdoctoral training with Dr. Tom Südhof, and acquired mouse genetics skills, in order to study animal models of human neurodegenerative diseases (Burré et al., 2010; Sharma et al., 2011). As an Assistant Professor of Neuroscience at Weill Cornell Medicine, Dr. Sharma’s lab studies neurodegenerative disorders at the molecular-cellular level, including their pharmacological correction-strategies (Naseri et al. 2020; Xie et al. 2022), frequently in collaboration with Dr. Jacqueline Burré’s lab.

Dr. Ellen Sidransky is the Branch Chief of the Medical Genetics Branch and is a pediatrician and geneticist in the National Human Genome Research Institute at National Institutes of Health (NIH). Dr. Sidransky received her B.A. from Brandeis University and her M.D. from Tulane University. She trained in pediatrics at Northwestern University, and in Clinical Genetics at the NIH. Dr. Sidransky has been a tenured NIH investigator and Section Chief since 2000. Her research interests include both clinical and basic aspects of Gaucher disease and Parkinson disease, studies of genotype/phenotype correlation and genetic modifiers, insights from mouse models, and novel treatment strategies. She played a lead role in establishing the association between glucocerebrosidase and parkinsonism. The author of over 200 publications, she continues to focus on the complexity encountered in “simple” Mendelian disorders, the role of lysosomal pathways in parkinsonism, and the development of small molecule chaperone therapy for Gaucher disease and for parkinsonism. She is the recipient of the 2019 Jay Van Andel Award for Outstanding Achievements in Parkinson’s Disease Research, the 2019 U.S. Public Health Service Meritorious Service Medal and the 2021 WORLDSymposium Roscoe O. Brady Award for Innovation and Accomplishment.

Dr. Van Den Berge pursued her education in Belgium and U.S.A. in three different engineering disciplines: Construction (M.Sc.Eng.), industrial (M.Sc.Eng.) and biomedical (Ph.D.). Subsequently, she moved to Denmark to join Professor Per Borghammer’s group as postdoc. Today, Dr. Van Den Berge is an independent Group Leader at the Department of Clinical Medicine, Aarhus University, and at the Nuclear Medicine Department & PET Center, Aarhus University Hospital. Driven by her passion to uncover complex mechanisms through multi-disciplinary techniques, Dr. Van Den Berge decided to pursue a career in multi-disciplinary research, which encompassed health, natural and engineering sciences. Dr. Van Den Berge has made great contributions to Parkinson’s research by developing the first body-first Parkinson’s disease animal model (Acta Neuropathol, 2019; Brain, 2021). Despite the increasing evidence that Parkinson’s disease may begin outside of the brain years before motor symptoms appear, most research has focused on modelling the disease in the brain only. Dr. Van Den Berge’s model closely replicates the human disease and involves peripheral organs and old age, providing a breakthrough in the field. This accomplishment has opened a new avenue of research that may provide invaluable insight into the early stages of Parkinson’s and help to identify new disease-modifying treatment targets.

Dr. Volpicelli-Daley earned her B.A. in Math and English Literature in college. Her Ph.D. in Neuroscience was earned at Emory University in the lab of Allan Levey, M.D., Ph.D. expert in Alzheimer’s disease and dementias. She also trained in cell biology at Yale University and neurodegenerative disease at the University of Pennsylvania. Dr. Volpicelli-Daley is currently associate professor with tenure at the University of Alabama at Birmingham. Her lab focuses on the how pathologic aggregates of alpha-synuclein contribute to motor and cognitive symptoms in Parkinson’s disease and Lewy body dementias. She is director of a Graduate Neuroanatomy Course and Director of an M.D./Ph.D. course about research in basic sciences. She was awarded the UAB Graduate Dean’s Excellence in Mentorship Award and Outstanding Roadmap Scholars Research Mentor Award.

Dr. Amanda Woerman received her B.A. in botany/microbiology and politics and government from Ohio Wesleyan University in 2008, and her Ph.D. in molecular medicine from The George Washington University in 2013. In July 2013, Dr. Woerman joined Dr. Stanley Prusiner’s laboratory at UCSF as a postdoctoral fellow, where she developed cellular assays for characterizing tau and alpha-synuclein prion strains in neurodegenerative disease. Dr. Woerman joined the faculty at UMass Amherst as an assistant professor in September 2019, where her lab is focused on using strain biology to develop novel diagnostics and therapeutics for neurodegenerative diseases.

Yang Yang’s research interest is assembling and accumulation mechanisms of various amyloids in Neurodegenerative diseases. Dr. Yang completed her Ph.D. in Biochemistry and Molecular biology at the Institute of Biophysics (IBP), Chinese Academy of Sciences in 2017. Then she worked as a research associate in the laboratory of Dr. Zihe Rao focusing on the research of GPCR and Gi-protein complex. Yang started her postdoctoral training in Dr. Sjors Scheres’ laboratory at the Medical Research Council, Laboratory of Molecular Biology to determine the structures of amyloid filaments. Yang explored and characterized the cryo-EM structures of amyloid-β (Aβ) filaments from human brains with Alzheimer’s disease, and α-synuclein filaments from Parkinson’s disease and dementia with Lewy bodies.