Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
3UG3TR002151-01S1
INTEGRATED MICROPHYSIOLOGICAL SYSTEM OF CEREBRAL ORGANOID AND BLOOD VESSEL FOR DISEASE MODELING AND NEUROPSYCHIATRIC DRUG SCREENING Preclinical and Translational Research in Pain Management NCATS COLUMBIA UNIVERSITY HEALTH SCIENCES LEONG, KAM W NEW YORK, NY 2018
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

The clinical utility of opioids for pain treatment is limited by its risk for developing opioid usage disorders (OUD). These untoward effects impose a severe burden on society and present difficult therapeutic challenges for clinicians. We propose to extend our cerebral organoid MPS to facilitate the investigation of neuronal response to opioids and identify cellular and molecular signatures in patients vulnerable to OUD. We have assembled a team with complementary expertise in clinical characterization of OUD, cerebral organoid MPS modeling, single cell RNA-seq technology, and functional characterization of neurons in a mesolimbic reward system to test the hypothesis that midbrain MPS is a clinically relevant pre-clinical model for study of opioid usage disorder.
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.
1UG3TR003149-01
hiPSC-based DRG Tissue Mimics on Multi-well Microelectrode Arrays as a Tissue Chip Model of Acute and Chronic Nociception 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 UNIVERSITY OF TEXAS DALLAS BLACK, BRYAN JAMES Dallas, TX 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:

Researchers will develop an innovative three-dimensional (3D) model of acute and chronic nociception using human induced pluripotent stem cell (hiPSC) sensory neurons and satellite glial cell surrogates. They will develop a tissue chip for modeling acute and chronic nociception based on 3D hiPSC-based dorsal root ganglion tissue mimics and a high-content, moderate-throughput microelectrode array. Researchers will demonstrate stable spontaneous and noxious stimulus-evoked behavior in response to thermal, chemical, and electrical stimulation challenges. They aim to demonstrate sensitivity to translational control via ligand receptor interactions between neuronal and non-neuronal cell types. They also will demonstrate the quantitative efficiency and preclinical efficacy of our system by detecting known ligand-based modulators of translational control and voltage-gated ion channel antagonists in a sensitized model of chronic nociception. Researchers will leverage the high-throughput nature of our tissue chip model to screen Food and Drug Administration–approved bioactive compounds.
3U24TR001597-04S1
TIN Supplement Clinical Research in Pain Management Pain Management Effectiveness Research Network (ERN) NCATS University of Utah Dean, Jonathan Michael Salt Lake City, UT 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.