Clinical Translational Core

Children's Hospital Intellectual and Developmental Disabilities Research Center
Clinical Translational Core

Center URL:
Core Personnel
: Stephanie Brewster, MS, CGC
: Kira Dies, ScM, CGC
: Robin Kleiman, PhD
: Lisa Prock, MD, MPH
Core Director: Mustafa Sahin, MD, PhD

Core Description

The aims of the Clinical Translational Core are to achieve the following objectives:

1. Translation: Accelerate the translation of our basic research discoveries into new cures for and biomarkers of pediatric nervous system disorders.
2. Collaboration: Develop effective new strategies for disease prevention and treatment through collaborations among Boston Children's Hospital's basic and clinical scientists in partnership with the IDDRC Cores and the external research community, especially other IDDRCs.
3. Training: Train future leaders of pediatric translational neuroscience.

The Clinical Translational Core is made up of two collaborative components, the human neuron core and translational services, and utilizes a proven infrastructure through the Translational Neuroscience Center, with focus on the unique translational requirements for targeting the developing central nervous system and intellectual disabilities



I. Human Neuron Core Component:

Objective: The Human Neuron Core operationalizes a new paradigm for disease modeling using human neurons derived from patients to support preclinical screening of potential drugs in a core facility aligned with a broad network of developmental neuroscience, neurology and stem cell expertise.

Services Provided: The Human Neuron Core provides two categories of service to investigators studying intellectual disability; one focuses on creating iPSC-derived neuron models of neurodevelopmental disorders and is managed by two PhD level supervisors with significant experience in stem cell biology. This is closely integrated with a second set of services managed by a PhD level supervisor with significant experience working with high-through screening equipment and miniaturization of cell based assays for drug screening. These services are further detailed below.

Human Neuron Differentiation and Phenotyping Services:
Assistant Directors: Pin-Fang (Ivy) Chen, PhD and Elizabeth Buttermore, PhD
• Patient and unaffected control family member sample preparation for reprogramming to iPSCs from PBMCs or skin biopsy.
• Coordinate reprogramming of patient samples to iPSC lines through the Harvard Stem Cell Institute iPSC core facility.
• Characterization and expansion of iPSC lines for differentiation into neurons.
• Differentiation of human iPSC lines into specialized neuronal cell types using standardized operating protocols (SOPs).
• Measures of spontaneous electrical activity from iPSC derived neurons using Axion Maestro Multi-electrode array platform.
• Characterization of neuronal morphology using the ThermoFisher Arrayscan XTI.
• To request core services, log into iLabs or contact the core:

Assay Development and Drug Screening:
Assistant Director: Lee Barrett, PhD
• Consultation and training for cell based assay development.
• Consultation and access to small molecule libraries for screening campaigns.
• Hourly fee-for-service access to research assistant to support screening campaigns.
• Hourly fee-for-service access to high-throughput screening equipment. The core facility houses 2 high content screening platforms that include a Hamamatsu FDSS7000ex and a Thermofisher ArrayScan XTi, as well as a range of liquid handling equipment.
• Hamamatsu FDSS7000EX kinetic reader has the capability of conducting measurements of fluorescence or luminescence in 384 wells at once, with time resolution of up to 40Hz. The equipment allows for measurements of changes in membrane potential and concentration of intracellular ions such as Ca2+ in primary cultures, stem cell-derived or trans-differentiated cells, or cell lines in a fast, accurate, parallel fashion.
• ThermoFisher's Arrayscan XTI is an image based High Content Screening instrument that features a temperature and CO2 controlled live cell chamber to assay cell biology over several days. The Arrayscan XTI has an integrated liquid handler to administer compounds of interest, well by well, capturing changes in fluorescence up to 10Hz with an enhanced CCD camera and 7 LED light source using 6 to 384 well labware.
• To request core services, log into iLABs or contact the core:

II. Translational Services Component:

Objective: To support IDDRC investigators in translational research planning, and implementation throughout the drug discovery pipeline, from preclinical to phase 2 clinical trials, including regulatory guidance, biostatistical support, recruitment of participants and controls, as well as biological sample and data distribution. Other resources available will include preclinical consultation for drug discovery efforts and training opportunities.

Services Provided:

• The Clinical Research and Regulatory Affairs Service offers consultative services to investigators in designing human studies, including the preparation of IRB and FDA submissions. Staff will provide project management services including assistance with study staff supervision, study monitoring and audit preparation. Additionally, the Service can facilitate access for IDDRC investigators to the Research Participant Registry (RPR), a recruitment registry of >21,500 individuals (children and adults) with typical and atypical development who are interested in research participation, as well as to a human neurobehavioral assessment core for phenotyping efforts.

• The Data Analysis Component provides biostatistical support during the planning phase of new clinical research projects, providing assistance with study design and power calculations. As projects progress, Kush Kapur, PhD, Senior Biostatistician at BCH and Assistant Professor of Neurology at Harvard Medical School, will provide assistance with data analysis and statistical hypothesis testing. For larger scale projects, further biostatistical support is available through the Clinical Research Program of Boston Children's Hospital. As needed, highly specialized biostatistical support is available to IDDRC investigators from the Harvard Clinical and Translational Research Center (Harvard Catalyst) for projects with complex study design.

• Preclinical Consultation Services are administered by Robin Kleiman, PhD who was recruited to Boston Children's Hospital from industry to provide drug discovery expertise to investigators building preclinical therapeutic programs for neuroscience related disorders. Dr. Kleiman advises investigators on strategies for target identification and validation, screening funnel and biomarker development or study design of preclinical drug trials. Dr. Kleiman can provide critical review of drug discovery grant applications to funding agencies or industry partners and advice for working with industry.

• The Bio-repository was originally established for the Department of Neurology in 2008 by Elizabeth Engle, MD to better understand causes and develop new therapies for neurological disorders. The collection has expanded to include blood samples, saliva, CSF, urine, skin punch and post-surgical brain tissue with collaborations across multiple departments. The goal is to spur future research by fellows and other researchers at BCH on already collected biological samples with phenotypic data for de-identified use in translational research and clinical trials

• To request core services, contact the TNC:


Last Edited: 01/09/17 12:00 AM by Theresa Trapilo