Funded Projects

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Project #	Project Title	Research Focus Area	Research Program	Administering IC Sort descending	Institution(s)	Investigator(s)	Location(s)	Year Awarded
3U24TR001597-04S1 Show Summary	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 Show Summary	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 Show Summary	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.
1UG3TR003148-01 Show Summary	Multi-organ-on-chip device for modeling opioid reinforcement and withdrawal, and the negative affective component of pain: a therapeutic screening tool.	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 CALIFORNIA LOS ANGELES	MAIDMENT, NIGEL T (contact); ASHAMMAKHI, NUREDDIN ; SEIDLITS, STEPHANIE KRISTIN; SVENDSEN, CLIVE NIELS	Los Angeles, CA	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 multi-organ, microphysiological systems (MPSs) based on human induced pluripotent stem cell-derived midbrain-fated dopamine (DA)/gamma-aminobutyric acid neurons on a three-dimensional platform that incorporates microglia, blood–brain barrier (BBB), and liver metabolism. RNA sequencing and metabolomics analyses will complement the primary DA release measure to identify novel mechanisms contributing to chronic opioid-induced plasticity in DA responsiveness. The chronic pain-relevant aspect of the model will be realized by examination of aversive kappa-mediated opioid effects on DA transmission in addition to commonly abused mu opioid receptor agonists, and by incorporation of inflammatory-mediating microglia. Incorporation of BBB and liver metabolism modules into the microphysiologic system platform will permit screening of drugs. Throughput will be increased by integration of online sensors for online detection of DA and other analytes. Researchers will use a curated set of 100 chemical genomics probes.
1UG3TR003090-01 Show Summary	Joint Pain on a Chip: Mechanistic Analysis, Therapeutic Targets, and an Empirical Strategy for Personalized Pain Management	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 PITTSBURGH AT PITTSBURGH	GOLD, MICHAEL S (contact); LIN, HANG	Pittsburgh, PA	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: The research team developed an in vitro multi-component joint on a chip (microJoint), in which engineered osteochondral complexes, synovium, and adipose tissues were integrated. This study will introduce sensory innervation into the microJoint and a neuron-containing microfluidic ally will be developed to innervate the microJoint. The osteoarthritis (OA) model will be created in the Neu-microJoint system. The research team will assess activation and/or sensitization of nociceptive afferents with electrophysiology, as well as neurite outgrowth. They will mechanically insult the Neu-microJoint and assess the emergence of “pain” in response to prolonged mechanical stress. Researchers will assess the impact of drugs used clinically for management of OA on OA models and will then use “omic” approaches to identify new biomarkers and therapeutic targets. Researchers will assess the impact of opioids—which they hypothesize will increase the rate of joint degeneration and potentiate the release of pain-producing mediators—on neural activity in the presence and absence of joint injury, as well as the integrity of all joint elements.