Stanford Movement Disorders Center Research
The Stanford Movement Disorder Center is at the forefront of basic science, clinical, and translational research in Parkinson’s disease and other movement disorders. Our basic scientists seek to understand how the brain works at the systems level by visualizing brain pathways critical to neurodegenerative diseases, such as Parkinson’s disease and Huntington’s disease. Our translational researchers uniquely probe these brain pathways by studying the brain’s electrical signals intraoperatively and by visualizing human brain connectivity via neuroimaging. Our clinical researchers recruit patients and healthy control subjects for observational studies aimed to understand clinical symptoms, such as cognitive impairment and imbalance, as well as interventional clinical trials aimed to investigate newly developed therapies and surgical techniques directly in patients.
Movement Disorders Research Programs
We are interested in understanding how immune responses promote neurological disease. Recent advances in human genetics, particularly for neurodegenerative disorders like Alzheimer’s disease, have highlighted a causal role of disrupted immune responses in disease pathogenesis. An injurious immune response may be a common denominator across many neurological disorders, both acute (brain trauma or stroke) and chronic (epilepsy, Parkinson’s disease, Alzheimer's for eg.). An understanding of how innate immune responses cause neurological disease will be essential if we are to develop disease-modifying therapies for our patients. Using systems biology approaches, we are identifying immune pathways that regulate immune metabolism and immune responses at the brain interface. Our objectives are (1) to understand how aberrant brain and/or peripheral innate immune responses cause synapse loss and contribute to the vulnerability of selected circuits in different neurologic disorders, and (2) to develop preventive and therapeutic strategies targeting these inflammatory pathways in patients with neurologic diseases.
The Bronte-Stewart Lab investigates the brain’s contribution to abnormal movement in human subjects, using synchronous brain recordings and quantitative kinematics, and how these are modulated with different frequencies and patterns of neurostimulation. Dr. Bronte-Stewart’s team was the first in the United States to implant a sensing neurostimulator and now have the largest cohort of implanted patients in the world. From these devices, they can record brain signals directly, and use the patient’s own neural activity to drive the first closed loop neurostimulation studies in Parkinson’s disease. This work has led to the first multicenter national clinical trial in closed loop deep brain stimulation for people with Parkinson’s disease, which Dr. Bronte-Stewart will lead. Other clinical trials conducted include a study of the neurodegeneration in HIV infection and the safety of young plasma infusions as a potential treatment for Parkinson's disease.
The Buckwalter lab studies how inflammatory responses after brain injury affect neurological recovery.
Jun Ding Lab
The Ding lab uses interdisciplinary approaches to dissect the functional organization of motor circuits, particularly cortico-thalamo-basal ganglia networks. The long-term scientific goal of the Ding Lab is to construct functional circuit diagrams and establish causal relationships between activity in specific groups of neurons, circuit function, animal motor behavior and motor learing, and, thereby, to decipher how the basal ganglia process information and guide motor behavior. In addition, we aim to further help construct the details of psychomotor disorder 'circuit diagrams,' such as changes in Parkinson's disease, drug abuse and addiction.
Greicius Lab (Functional Imaging in Neuropsychiatric Disorders)
The Greicius lab uses imaging, genetics, and imaging genetics to better understand Alzheimer’s disease and related disorders from the level of molecular pathways to large-scale distributed brain networks and behavior. Recent and ongoing work leverages the APOE4 genetic variation that increases risk for Alzheimer’s disease. In the Stanford Extreme Phenotypes in Alzheimer’s Disease (StEP AD) study, the lab is looking for protective genetic variants in healthy older subjects that have 1 or 2 copies of the high-risk APOE4 gene but do not show signs of Alzheimer’s disease. The StEP AD study is also looking at the for novel causal genetic mutations in patients with early-onset Alzheimer’s disease who do not have the APOE4 variant. All participants undergo “deep phenotyping” including molecular imaging, immunophenotyping, and blood/spinal fluid biomarkers. The expectation is that novel protective or causal variants identified in the StEP AD study will provide novel targets for drug development.
The primary aim of the James Lab is to improve the diagnosis and treatment of brain diseases by developing translational molecular imaging agents for visualizing neuroimmune interactions underlying conditions such as Alzheimer’s disease, multiple sclerosis, and stroke. We are researching how the brain and its resident immune cells interact with the peripheral immune system at very early, through to late, stages of disease. Our approach involves the discovery and characterization of clinically relevant immune cell biomarkers, followed by the design of imaging agents specifically targeting these biomarkers. After preclinical validation, we translate promising imaging probes to the clinic to enable precision targeting of immunomodulatory therapeutics and real-time monitoring of treatment response.
The Lee Lab uses interdisciplinary approaches from biology and engineering to analyze, debug, and manipulate systems-level brain circuits. We seek to understand the connectivity and function of these large-scale networks in order to drive the development of new therapies for neurological diseases. This research finds its basic building blocks in areas ranging from medical imaging and signal processing to genetics and molecular biology.
Dr. Longo and his research team are focused on elucidating mechanisms underlying neurodegenerative disorders and developing small molecule therapeutic strategies that target these mechanisms. Neurotrophin proteins bind to multiple receptors (p75, TrkA-C) to modulate survival, functional and degenerative intracellular signaling and synaptic function. The Longo laboratory and collaborators pioneered the mechanistic principle that non-peptide small molecules targeting individual receptor epitopes can activate or modulate neurotrophin receptors to produce distinctive biological effects capable of inhibiting disease mechanisms. This work has led to successful efficacy trials in many mouse models of neurodegenerative disorders including Alzheimer’s, Huntington’s, and Parkinson’s diseases as well as spinal cord injury, traumatic brain injury, chemotherapy-induced neuropathy, ischemic stroke recovery, Rett syndrome, and epilepsy. One of our small molecules, the p75NTR ligand, LM11A-31, has progressed through a human phase 1 safety trial and is in a phase 2a Alzheimer’s disease trial ongoing in Europe. We have been fortunate to execute the rare full translational spectrum of: identifying novel basic mechanisms, creating novel entities to target those mechanisms, moving these therapeutic candidates through mouse and other pre-clinical studies, progressing one of these candidates to first-in-human safety studies and testing of the first-in-class therapeutic entity in neurodegenerative disease subjects.
Menon Lab (Stanford Cognitive & Systems Neuroscience Laboratory)
The Stanford Cognitive and Systems Neuroscience Laboratory (SCSNL), led by Dr. Vinod Menon, aims to transform the global landscape of psychiatry research and human health and wellness. Leveraging expertise in neuroscience, statistics, engineering, computer science, psychology, psychiatry, and neurology, researchers in the lab use advanced multimodal brain imaging techniques, novel computational and statistical methods, and clinical-behavioral assays to investigate the architecture, function, and development of the human brain in psychiatric and neurological disorders. Clinical disorders currently under investigation include learning disabilities, autism, ADHD, anxiety and mood disorders, and schizophrenia.
The focus of the Montine Laboratory is on the structural and molecular bases of cognitive impairment with the goal of defining key pathogenic steps and thereby new therapeutic targets. The Montine Laboratory addresses these prevalent, unmet medical needs through a combination of neuropathology, biomarker development and application early in the course of disease, and experimental studies that test hypotheses concerning specific mechanisms of neuron injury and approaches to neuroprotection.
Our overall research objective is to understand the risk of Alzheimer’s disease before clinical symptoms of dementia are present. To study the earliest stages of Alzheimer’s disease, we take a multimodal approach to deeply phenotype our human research volunteers. Our studies integrate information from molecular PET imaging (especially Amyloid and Tau PET), MRI scans that provide information about brain structure and function, lumbar puncture to investigate the biomarkers in the cerebrospinal fluid, sensitive neuropsychological measurements, and genetics. Our hope is that the combination of these data types will improve our ability to predict who is most at risk for dementia decades before clinical symptoms are present.
At the Poston Lab, we seek understand the cognitive and other non-motor impairments that develop in patients with alpha-synuclein pathology, such as Parkinson’s disease, Lewy body dementia, and Multiple System Atrophy. Our lab uses functional and structural imaging, along with biological and genetic biomarkers, to determine the underlying pathophysiologies that cause these impairments, with the ultimate goal of aiding the development of new therapies.