Post Doctoral Research Fellow

About the Role

This is a combined position as a Postdoctoral Fellow and Manager of the McLean Hospital Microscopy Core at McLean Hospital and Harvard Medical School. The role offers a distinctive opportunity to pursue research on the cellular and molecular mechanisms underlying psychiatric disorders while providing scientific and operational leadership for a shared advanced-microscopy facility.

Postdoctoral Research Program

The postdoctoral fellow will contribute to a multidisciplinary research program examining how stress and immune signaling affect interactions among neurons, glia, and the neurovascular unit (NVU). The NVU—including brain endothelial cells, pericytes, astrocytes, microglia, neurons, and the vascular basal lamina—is positioned at the interface between systemic and neural processes and may play a critical role in translating immune, metabolic, and other stress-related challenges into altered neural function and psychiatric symptoms.

The research investigates the hypothesis that stress-related symptom dimensions—including anxiety, irritability, depression, and anhedonia—are associated with dysregulation of NVU homeostatic reserve: the capacity of NVU cells to respond adaptively to stress and immune challenges. Studies will examine coordinated gene-expression programs across neuronal, glial, and vascular cell populations and determine how their disruption relates to clinically relevant symptom dimensions across psychiatric diagnoses.

The fellow will work with deeply characterized human postmortem brain specimens, primarily from the amygdala and anterior cingulate cortex, and with cellular preparations derived from the same donors. Molecular, cellular, and morphological findings will be integrated with transdiagnostic clinical phenotypes derived from extensive health records using natural-language-processing approaches.

Research Activities

• Advanced fluorescence, confocal, two-photon, and electron microscopy
• Quantitative image analysis and three-dimensional reconstruction
• Multiplex in situ RNA and protein detection in human brain tissue
• Morphological and cytoarchitectonic analyses of neurons, glia, microvasculature, and other NVU components
• Primary human astrocyte, microglial, and brain endothelial cell cultures derived from postmortem tissue
• iPSC-derived glial and vascular cell models, including comparisons with primary cells and native tissue from the same donors
• Experiments examining cellular responses to cytokines, stress neuropeptides, and immune or metabolic challenges
• Single-cell or single-nucleus transcriptomic studies of brain tissue, isolated microvasculature, and cultured cells
• Integration of molecular, cellular, morphological, and functional measures with transdiagnostic dimensions of stress-related symptoms

The fellow will be encouraged to develop independent research questions within this program and will contribute to experimental design, data analysis and interpretation, scientific presentations, manuscript preparation, and grant applications.

Microscopy Core Management

In parallel with the postdoctoral research program, the successful candidate will manage the scientific, technical, operational, and financial activities of the McLean Hospital Microscopy Core. The Core Manager will serve as a front-line scientific resource for McLean investigators and external users, providing expert guidance on microscopy-based study design, sample preparation, data acquisition, image processing, and quantitative analysis. The Core Manager will oversee the overall functioning of the facility, coordinate instrument access and maintenance, train and support users, supervise contracted technical services, and serve as a liaison among investigators, hospital administrative units, vendors, and external service providers. The role also includes consultation on microscopy-related methods, project feasibility, budgeting, and appropriate use of Core resources.

Transmission Electron Microscopy Responsibilities

• Maintain the Reichert-Jung ultramicrotome and ancillary TEM equipment
• Oversee the operation and maintenance of the JEOL JEM1200EX transmission electron microscope and associated cooling systems
• Conduct TEM studies for McLean and external investigators
• Provide expertise in resin embedding, sample preparation, ultramicrotomy, staining, image acquisition, and image processing
• Perform and support immuno-electron microscopy
• Perform cryopreservation and freeze substitution of biological specimens
• Conduct electron tomography on ultrathin sections and reconstruct tomographic datasets
• Perform negative staining for appropriate biological samples
• Prepare specialized sample supports, including Formvar- and carbon-coated grids, glow-discharged grids, and grids containing gold fiducial markers
• Advise investigators on experimental design, sample suitability, controls, and interpretation of ultrastructural findings
• Coordinate and supervise on-site contracted TEM maintenance and repair services

Laser-Scanning Confocal Microscopy Responsibilities

• Train users in independent operation of the Leica SP8-TCS laser-scanning confocal microscope
• Train and support users in image acquisition, processing, visualization, and quantitative analysis
• Provide consultation on fluorophore selection, spectral separation, imaging parameters, controls, resolution, sampling, and avoidance of imaging artifacts
• Perform confocal microscopy for McLean and external investigators when specialized assistance is required
• Maintain the confocal microscope and associated hardware and software in optimal operating condition
• Diagnose technical problems and coordinate preventive maintenance, repairs, and software or hardware upgrades
• Supervise on-site contracted services related to the confocal system

Two-Photon Laser-Scanning Microscopy Responsibilities

• Train users to operate the Olympus FV-MPE-RS two-photon microscope and Spectra-Physics InSight DeepSee Duo laser system
• Provide guidance on experimental design, image acquisition, image processing, and quantitative analysis for two-photon applications
• Support investigators in optimizing imaging parameters for fixed tissue, living preparations, and other appropriate applications
• Maintain the microscope, laser system, environmental components, and associated software in optimal working condition
• Coordinate and supervise preventive maintenance, repair, and other contracted services related to the two-photon system

Core Operations and Research Administration

• Develop and maintain a structured, equitable user registration and instrument-scheduling system
• Establish and maintain instrument-specific training, authorization, and competency records
• Develop, update, and enforce standard operating procedures for instrument use, sample preparation, data management, and laboratory safety
• Monitor instrument usage, performance, service history, and user needs
• Ensure compliance with laboratory safety, security, biosafety, chemical handling, and hazardous-waste-disposal requirements
• Maintain adequate inventories of laboratory consumables, reagents, replacement parts, and essential supplies
• Coordinate relationships with vendors, service engineers, contractors, and institutional administrative units
• Assist investigators with microscopy-related study design, feasibility assessment, cost estimates, and budget preparation
• Maintain accurate records of Core projects, users, instrument time, services, and technical support
• Contribute to strategic planning for equipment replacement, upgrades, and acquisition of new imaging technologies
• Promote effective and rigorous use of microscopy resources across the McLean research community

Fiscal Management Responsibilities

• Generate and issue monthly invoices for instrument usage and Core services
• Develop and manage the annual operating budget for the Microscopy Core
• Track service contracts, maintenance expenses, consumables, user charges, and other Core expenditures
• Maintain detailed and accurate financial records
• Assist in establishing and periodically reviewing instrument and service rates
• Provide usage and financial reports to departmental and institutional leadership as requested
• Contribute technical information and budget estimates for grants involving Core instrumentation or services

Qualifications

Candidates should hold a PhD, MD, or equivalent doctoral degree in neuroscience, cell biology, molecular biology, biomedical imaging, neuropathology, or a related discipline. The position requires substantial hands-on experience with advanced microscopy and the scientific leadership to manage a shared core facility.