Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1UG3TR003150-01
Human Microphysiological Model of Afferent Nociceptive Signaling Preclinical and Translational Research in Pain Management Translational Research to Advance Testing of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder NCATS TULANE UNIVERSITY OF LOUISIANA MOORE, MICHAEL J (contact); ASHTON, RANDOLPH S; RAJARAMAN, SWAMINATHAN New Orleans, LA 2019
NOFO Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-TR-19-003
Summary:

This project will develop a human cell-based model of the afferent pain pathway in the dorsal horn of the spinal cord. The research team’s approach utilizes novel human pluripotent stem cell (hPSC)-derived phenotypes in a model that combines 3D organoid culture with microfabricated systems on an integrated, three-dimensional (3D) microelectrode array. Researchers will establish the feasibility of a physiologically relevant, human 3D model of the afferent pain pathway that will be useful for evaluation of candidate analgesic drugs. They will then improve the physiological relevance of the system by promoting neural network maturation before demonstrating the system’s utility in modeling adverse effects of opioids and screening compounds to validate the model. Completion of the study objective will establish novel protocols for deriving dorsal horn neurons from hPSCs and create the first human microphysiological model of the spinal cord dorsal horn afferent sensory pathway.
3R44TR001326-03S1
Automation and validation of human on a chip systems for drug discovery Cross-Cutting Research Small Business Programs NCATS HESPEROS, LLC SHULER, MICHAEL L; HICKMAN, JAMES J Orlando, FL 2019
NOFO Title: PHS 2017-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44])
NOFO Number: PA-17-302
Summary:

Hesperos uses microphysiological systems in combination with functional readouts to establish systems capable of analysis of chemicals and drug candidates for toxicity and efficacy during pre-clinical testing, with initial emphasis on predictive toxicity. The team constructed physiological systems that represent cardiac, muscle and liver function, and demonstrated a multi-organ functional cardiac/liver module for toxicity studies as well as metabolic activity evaluations. In addition, the team demonstrated multi-organ toxicity in a 4-organ system composed of neuronal, cardiac, liver and muscle components. While much is known about the cells and neural circuitry regulating pain modulation there is limited knowledge regarding the precise mechanism by which peripheral and spinal level antinociceptive drugs function, and no available human-based model reproducing this part of the pain pathway. The ascending pain modulatory pathways provide a well characterized neural architecture for investigating pain regulatory physiology. In this project, the research team propose a human-on-a-chip neuron tri-culture system composed of nociceptive neurons, GABAergic interneurons and glutamatergic dorsal projection neurons (DPN) integrated with a MEMS construct. Using this model, investigators will interrogate pain signaling physiology at three levels, 1) at the site of origin by targeting nociceptive neurons with pain modulating compounds including noxious stimuli and inflammatory mediators, 2) at the inhibitory GABAergic interneuron, and 3) at the ascending spinal level by targeting glutamatergic DPNs. These circuits will be integrated utilizing expertise in patterning neurons as well as integration with BioMEMs devices. This system provides scientists with a better understanding of ascending pain pathway physiology and enable clinicians to consider alternative indications for treating pain at peripheral and spinal levels. 
1DP2TR004354-01
Scale Up Single-Cell Technologies to Map Pain-Associated Genes and Cells Across the Lifespan Cross-Cutting Research Training the Next Generation of Researchers in HEAL NCATS Massachusetts General Hospital SHU, JIAN Boston, MA 2022
NOFO Title: Emergency Awards: HEAL Initiative- New Innovator Award (DP2 Clinical Trial Not Allowed)
NOFO Number: RFA-tr-22-013
Summary:

Current treatments for chronic pain, including opioids, are not effective for many individuals. Much remains unknown about genes, circuits, and cells that contribute to chronic pain, including how chronic pain changes across the lifespan in certain populations, including infants, children, older people, and pregnant women. This project will develop technology to map the genes, circuits, and cells associated with pain across ages, sexes, and during pregnancy. The technologies will guide the search for new biomarkers for chronic pain diagnosis and treatments.
3U24TR001608-04S1
TIN Supplement Clinical Research in Pain Management Pain Management Effectiveness Research Network (ERN) NCATS Duke University Benjamin, Daniel K. Durham, NC 2019
NOFO Title: CTSA Network - Trial Innovation Centers (TICs) (U24)
NOFO Number: RFA-TR-15-002
1R21TR004701-01
Exploration of MBD1 as a Therapeutic Target for Chronic Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NCATS UNIVERSITY OF MINNESOTA STONE, LAURA S Minneapolis, MN 2023
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: RFA-TR-22-011
Summary:

Chronic pain results in long-term changes throughout the central nervous system. These include abnormal structure and function of the frontal cortex region of the brain, which relays pain messages and also the common pain-related conditions depression, anxiety, and cognitive impairment. Peripheral nerve injury results in widespread and long-lasting changes to DNA in the frontal cortex. DNA methylation, in which chemical tags are attached to DNA, is one way the body controls the activity of genes over time. This control occurs via proteins that recognize tagged DNA, and some of these proteins do not work properly in the frontal cortex many months after nerve injury. These changes occur after nerve injury and are linked to mechanical sensitivity. This project will determine this DNA-binding protein is a good target for finding new medications for chronic pain.