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APDA Center for Advanced Research

The APDA Center for Advanced Research at Brigham and Women’s Hospital, led by , is dedicated to unlocking a deeper understanding of Parkinson’s disease (PD) patients and its diverse manifestations. The center’s mission is to develop precise, patient-focused therapies that improve outcomes for individuals living with PD. Brigham and Women’s provides the infrastructure to support research into genetic variants, neuromodulation techniques, and molecular stratification.

The Center collaborates with leading research entities affiliated with Brigham and Women’s and Harvard Medical School. This includes the Ann Romney Center for Neurologic Disease, which focuses on molecular neuroscience and neuroimmunology, and the Center for Brain Circuits Therapeutics, which specializes in brain-network and neuromodulatory approaches.

By combining resources like the Harvard Biomarkers Study (HBS) and the , the Center can leverage over 15 years of biomarker data. These tools enable robust, longitudinal studies involving thousands of patients.

A key strength of the Center is its deep expertise in induced pluripotent stem cell (iPSC) models. By creating patient-derived stem cell models, researchers can simultaneously conduct clinical trials and accelerate the pace of drug discovery through personalized medicine. These same models, paired with whole-genome sequencing and epidemiologic studies, are used to better understand how specific gene-environment interactions lead to the alpha-synuclein misfolding—a central mechanism in PD risk and progression.

Our Teams and Projects

Systems cell biology and genomics
  • PI: Vik Khurana
  • Co-PI: ; ; and
  • Research questions:
    • What is the molecular and cellular basis of phenotypic heterogeneity in PD?
    • How do these factors relate to alpha-synuclein biology?
Systems circuit biology
  • PI:
  • Co-PI:
  • Research questions:
    • How does specific central nervous system circuit dysfunction related to altered phenotypes in PD?
    • Can we overlay gene expression maps with circuit dysfunction maps to achieve a deeper understanding of PD heterogeneity?
Systems environmental biology
  • Co-PIs: ; ; and
  • Collaborating PI:
  • External collaborator: Beate Ritz, MD, PhD
  • Research questions:
    • How do factors outside the CNS—such as environmental toxicants, immune/infectious factors, and gut microbiota—affect PD outcomes?
Infrastructure #1: HBS 2.0
  • PI: Vik Khurana
  • Co-PIs: Barbara (Kelly) Changizi, MD, Jennifer Liu, MD and Diego Rodriguez, MD
  • Manager: Daniel El-Kodsi, PhD
  • Summary:
    • Longitudinal biospecimens were collected from 2,000 PD patients, including:
      • Whole blood, plasma, peripheral blood mononuclear cells (PBMCs), cerebrospinal fluid (CSF)
      • Clinical data (MDS-UPDRS, MMSE, TUG, MoCA, H&Y, self-assessment)
      • PBMCs/fibroblasts/iPSC
      • Whole-genome sequencing
    • More than 400 patients are currently being enrolled for prospective sample collection, with recruitment ongoing since 2024.
Infrastructure #2: CLIMB
  • PI:
  • Manager: Bonnie Glanz, PhD
  • Summary: Immune analysis-focused biospecimens were collected longitudinally from more than 1,000 patients (MS, AD, PD, MSA), including:
    • Serum, plasma, and PBMCs
    • Stool for gut microbiota without chemical preservatives

Exciting Developments in PD Treatments

Innovative approaches targeting specific brain networks and neuromodulatory pathways are driving some of the most exciting advancements in PD treatment. The APDA Center at Brigham and Women’s is pioneering methods to better understand and manipulate these brain circuits, particularly through the Center for Brain Circuits Therapeutics. This work focuses on refining and expanding neuromodulatory treatments, such as deep brain stimulation (DBS) and focused ultrasound, to enhance treatment outcomes.

Another promising area of development is precision medicine for PD. The Center is advancing biomarker-based patient stratification, using genetic and molecular markers to classify PD patients and tailor treatments more effectively. Leveraging one of the world’s largest brain-matched iPSC repositories, researchers can model PD in the lab to better understand disease mechanisms and identify potential therapies.

Recent drug developments, including novel classes of drugs like stearoyl-coA desaturase inhibitors, are being studied to better match them to the right patients. The MyTrial program enables parallel trials in patients and “in the dish,” accelerating the process of matching drugs and biologics to specific patient profiles. This innovative capability has attracted interest from leading biopharmaceutical companies eager to leverage the Center’s expertise.

Additionally, cutting-edge genetic and AI tools developed at the Center have led to promising new disease targets related to PD progression. To date, two biotech companies have spun out from the APDA Center, transforming discoveries in the Center into real-world drug development.

Training and Development of PD Researchers

The APDA Center take a holistic, interdisciplinary approach to training the next generation of PD researchers. Situated within the Hale Building for Transformative Medicine in Boston’s renowned Longwood Medical Area, Brigham and Women’s offers trainees a unique opportunity to gain hands-on experience in both clinical and laboratory settings under one roof.

Training is structured through joint fellowships with Massachusetts General Hospital, focusing on movement disorders or neurogenetics. Trainees benefit from an exceptional range of research opportunities, spanning molecular and cellular neuroscience, stem-cell modeling, functional genomics, statistical genetics, AI methodology, biobanking, biomarker development (including PET imaging, MRI and biometrics), as well as gene and neuromodulatory therapies.

Each year, the Center funds and mentors two to three senior trainees, guiding them through distinct research projects that encourage collaboration across institutions and disciplines. Current trainees work closely with leaders in genomics, neurology, and neuroimmunology.

The Hale Building brings together diverse neuroscience specialties, fostering an immersive training experience within a vibrant, collaborative environment. This comprehensive approach equips researchers with expertise in PD-specific methodologies and prepares them to lead multidisciplinary and cross-cutting projects.

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