Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
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.
1R43TR004743-01
The Pain in a Dish Assay (PIDA): A High Throughput System Featuring Human Stem Cell-Derived Nociceptors and Dorsal Horn Neurons to Test Compounds for Analgesic Activity Cross-Cutting Research Small Business Programs NCATS VALA SCIENCES, INC. MCDONOUGH, PATRICK M San Diego, CA 2023
NOFO Title: HEAL INITIATIVE: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-23-006
Summary:

This project will develop PIDA, which will allow researchers to measure the activity of pain-sensitive human neurons in response to pain stimuli and potential pain treatments. The tool will use automated digital microscopes in the absence or presence of a potential pain medication. Since this tool contains human neurons, it may be more effective at predicting the efficacy of potential pain drugs in human patients than the animal models that are currently used.
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
3UG3TR003149-02S1
Supplement to 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 Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NCATS UNIVERSITY OF TEXAS DALLAS BLACK, BRYAN JAMES Dallas, TX 2020
NOFO Title: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008
Summary:

This study aims to determine whether a subset of understudied genes that are expressed in human and mouse dorsal root ganglia (DRG) tissues (critical for relaying the sensation of pain from the body to the central nervous system), are also expressed in human induced pluripotent stem cell DRG mimetics. The study will also determine if these genes are involved in neuronal excitability changes under inflammatory conditions and compare these responses to those of primary DRG neurons. Third and finally, the study will optimize genetic depletion of target genes enabling future fundamental and preclinical research studies.
1UG3TR003081-01
Multi-organ human-on-a-chip system to address overdose and acute and chronic efficacy and off-target toxicity 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 CENTRAL FLORIDA HICKMAN, JAMES J (contact); SHULER, MICHAEL L Orlando, FL 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 build overdose models for fentanyl, methadone, codeine, and morphine in a multi-organ system and evaluate the acute and repeat dose, or chronic effects, of overdose treatments as well as off-target toxicity. Researchers developed a system using human cells in a pumpless multi-organ platform that allows continuous recirculation of a blood surrogate for up to 28 days. They will develop two overdose models for male and female phenotypes based on pre-B?tzinger Complex neurons and will integrate functional immune components that enable organ-specific or systemic monocyte actuation. Models for cardiomyopathy and infection will be utilized. Researchers will establish a pharmacokinetic/pharmacodynamic model of overdose and treatment to enable prediction for a range of variables. We will use a serum-free medium with microelectrode arrays and cantilever systems integrated on chip that allow noninvasive electronic and mechanical readouts of organ function.