A5080942774- Pain Mechanisms and Treatments
- Hereditary Neurological Disorders
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Nerve injury and regeneration
- Botulinum Toxin and Related Neurological Disorders
- Cancer Treatment and Pharmacology
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Peripheral Neuropathies and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Exercise and Physiological Responses
- CAR-T cell therapy research
- Spine and Intervertebral Disc Pathology
- Neurobiology and Insect Physiology Research
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Blood Coagulation and Thrombosis Mechanisms
- Genetic Neurodegenerative Diseases
- Long-Term Effects of COVID-19
- Anatomy and Medical Technology
- Pain Management and Placebo Effect
- Dermatology and Skin Diseases
- Neuroscience and Neural Engineering
The University of Texas at Dallas
2018-2025
Washington University in St. Louis
2025
University of Dallas
2024
Qiagen (Switzerland)
2024
Johns Hopkins University
2024
Sensory neurons in the dorsal root ganglion (DRG) and trigeminal (TG) are specialized to detect transduce diverse environmental stimuli central nervous system. Single-cell RNA sequencing has provided insights into diversity of sensory ganglia cell types rodents, nonhuman primates, humans, but it remains difficult compare across studies species. We thus constructed harmonized atlases DRG TG that describe facilitate comparison 18 neuronal 11 non-neuronal six species 31 datasets. then performed...
Abstract Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus–detecting sensory neurons, called nociceptors. A key feature of this following priming, stimuli do not normally cause hyperalgesia now readily provoke state. We hypothesized hyperalgesic occurs because reorganization translation mRNA To test hypothesis, we paclitaxel treatment as the stimulus and translating ribosome affinity purification measure persistent changes Na v 1.8+...
Abstract Cell states are influenced by the regulation of gene expression orchestrated transcription factors capable binding to accessible DNA regions. To uncover if sex differences exist in chromatin accessibility human dorsal root ganglion (hDRG), where nociceptive neurons innervating body found, we performed bulk and spatial assays for transposase-accessible technology followed sequencing (ATAC-seq) from organ donors without a history chronic pain. Using ATAC-seq, detected abundant hDRG....
Abstract Peripheral sensory neurons in the dorsal root ganglion (DRG) and trigeminal (TG) are specialized to detect transduce diverse environmental stimuli including touch, temperature, pain central nervous system. Recent advances single-cell RNA-sequencing (scRNA-seq) have provided new insights into diversity of ganglia cell types rodents, non-human primates, humans, but it remains difficult compare transcriptomically defined across studies species. Here, we built cross-species harmonized...
Neuroimmune interactions are essential for the development of neuropathic pain, yet contributions distinct immune cell populations have not been fully unraveled. Here, we demonstrate critical role B cells in promoting mechanical hypersensitivity (allodynia) after peripheral nerve injury male and female mice. Depletion with a single injection anti-CD20 monoclonal antibody at time prevented allodynia. cell–deficient (muMT) mice were similarly spared from Nerve was associated increased...
Chronic pain patients suffer from pain-related cognitive deficits, even when taking commonly prescribed analgesics. These deficits are likely related to maladaptive plasticity in the frontal cortex. We sought model mice with neuropathic examine morphological mPFC and assess effects of several therapeutics. used an attentional set-shifting task spared nerve injury (SNI) who received either a single intrathecal injection analgesic dose clonidine, 7 d 100 mg/kg gabapentin, or 200 metformin....
Chemotherapy-induced peripheral neuropathy (CIPN) is a primary dose-limiting side effect caused by antineoplastic agents, such as paclitaxel. A symptom of this pain. Currently, there are no effective treatments for CIPN, which can lead to long-term morbidity in cancer patients and survivors. Neuro-immune interactions occur CIPN pain have been implicated both the development progression resolution CIPN. We investigated potential role inducible co-stimulatory molecule (ICOS) pain-like...
Abstract Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain patients suffering from this largely untreated disease. While many intracellular signalling mechanisms have been examined preclinical models that drive spontaneous activity, none tested directly on spontaneously active human nociceptors. Using cultured DRG recovered during thoracic vertebrectomy surgeries, we showed inhibition mitogen-activated protein kinase interacting (MNK) with...
Abstract Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain preclinical models and patients suffering from this largely untreated disease. While many intracellular signaling mechanisms have been examined that drive spontaneous (SA), none these tested directly on spontaneously active human nociceptors. Using cultured DRG recovered during thoracic vertebrectomy surgeries, we show inhibition mitogen activated protein kinase interacting (MNK) with...
Plasticity of dorsal root ganglion (DRG) nociceptors in the peripheral nervous system requires new protein synthesis. This plasticity is believed to be responsible for physiological changes seen DRG animal models chronic pain. Experiments human (hDRG) neurons also support this hypothesis, but a direct observation nascent synthesis response pain promoting substance, like interleukin-6 (IL-6), has not been measured these neurons. To fill gap knowledge, we used acutely prepared explants from...
Despite the prevalence of chronic pain, approval novel, non-opioid therapeutics has been slow. A major translational challenge in analgesic development is difference gene expression and functional properties between human rodent dorsal root ganglia (DRG) sensory neurons. Extensive work rodents suggests that sensitization nociceptors DRG essential for pathogenesis persistence pain; however, direct evidence demonstrating similar physiological humans limited. Here, we examine whether pain...
RNA sequencing studies on human dorsal root ganglion (hDRG) from patients suffering neuropathic pain show upregulation of OSM, linking this IL-6 family cytokine to disorders. In mice, however, OSM signaling causes itch behaviors through a direct effect its cognate receptor expressed uniquely by pruriceptive sensory neurons. We hypothesized that an expansion in function OSM-OSM (OSMR) disorders humans could be explained species differences expression and signaling. Our situ hybridization...
Abstract Phosphorylation of hundreds protein extracellular domains is mediated by two kinase families, yet the significance these kinases underexplored. Here, we find that presynaptic release tyrosine directed-ectokinase, Vertebrate Lonesome Kinase (VLK/Pkdcc), necessary and sufficient for direct interaction between EphB2 GluN1 at synapses, phosphorylation ectodomain EphB2, injury-induced pain. Pkdcc an essential gene in nervous system, VLK found synaptic vesicles, released from neurons a...
Abstract Splicing is a posttranscriptional RNA processing mechanism that enhances genomic complexity by creating multiple isoforms from the same gene. We aimed to characterize expressed in human peripheral nervous system, with goal of resource identify novel functionally relevant genes associated somatosensation and nociception. used long-read sequencing document isoform expression dorsal root ganglia 3 organ donors validated silico confirming short-read independent donors. Nineteen thousand...
Purpose Describe the human nervous tissue removal, preservation, storage, and transportation procedures during procurement from organ donors. Responsibility The Human Tissue Procurement Processing core at University of Texas Dallas is responsible for maintaining this protocol, ensuring it updated controlled, that users receive proper training prior to its implementation. Definitions Abbreviations aCSF = artificial cerebral spinal fluid BD Brain Dead COD Cause Death CTOD Called Time DCD...
Protease-activated receptor 2 (PAR2) has long been implicated in inflammatory and visceral pain, but the cellular basis of PAR2-evoked pain not delineated. Although attributed to sensory neuron expression, RNA-sequencing experiments show ambiguous F2rl1 mRNA detection. Moreover, many pharmacological tools for PAR2 are nonspecific, acting also on Mas-related GPCR family (Mrg) that highly enriched neurons. We sought clarify pain. developed a PAR2–conditional knockout mouse specifically deleted...
Cognitive deficits in schizophrenia are linked to dysfunctions of the dorsolateral prefrontal cortex (DLPFC), including alterations parvalbumin (PV)-expressing interneurons (PVIs). Redox dysregulation and oxidative stress may represent convergence points pathology schizophrenia, causing dysfunction GABAergic loss PV. Here, we show that mitochondrial matrix protein cyclophilin D (CypD), a critical initiator permeability transition pore (mPTP) modulator intracellular redox state, is altered...
Abstract Gene expression is influenced by chromatin architecture via controlled access of regulatory factors to DNA. To better understand gene regulation in the human dorsal root ganglion (hDRG) we used bulk and spatial transposase-accessible technology followed sequencing (ATAC-seq). Using ATAC-seq, detected that females diverse differentially accessible regions (DARs) mapped X chromosome males autosomal genes. EGR1/3 SP1/4 transcription factor binding motifs were abundant within DARs...
Abstract CRISPR-Cas9 editing is now the leading method for genome and being advanced treatment of human disease. CRIPSR could have many applications neurological diseases, including pain but traditional viral vector delivery approaches neurotoxicity limiting their use. Overcoming these issues open door treatments diseases like intractable where dorsal root ganglia (DRG) would be desired target. To this end, we describe a simple viral-vector-independent transfection primary DRG (hDRG) neurons...