Human Nociceptor and Spinal Cord Molecular Signature Center

人类伤害感受器和脊髓分子特征中心

基本信息

批准号：
10770232
负责人：
Michele Curatolo
金额：
$ 7.78万
依托单位：
UNIVERSITY OF TEXAS DALLAS
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-19 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10770232
关键词：
Adult Afferent Neurons Animal Model Animals Architecture Biological Assay Brain Cancer Center Cell Nucleus Cells Chest Chronic disabling pain Chronic low back pain Chronic neck pain Collaborations Communication Complex Data Disease Ensure Foundations Generations Genome Genomics Goals Human Immunohistochemistry Individual Information Resources Longevity Low Back Pain Maps Methods Microfluidics Modeling Molecular Molecular Analysis Molecular Profiling Mus Nature Nerve Neurons Nociception Nociceptors Operative Surgical Procedures Organ Donor Pain Pain management Pathway interactions Patients Peripheral Peripheral Nerves Pharmacology Physiological Population Heterogeneity Posterior Horn Cells Price Process Productivity Protocols documentation Publications Publishing Quality Control RNA Research Personnel Research Project Grants Resolution Resources Sampling Sex Differences Signal Transduction Spinal Spinal Cord Spinal Ganglia Split-Pool Ligation Transcriptome sequencing Synapses Techniques Technology Therapeutic Tissue Procurements Tissues Translations Universities Vertebral column Washington Work cell type chronic pain chronic painful condition conflict resolution connectome data resource dorsal horn empowerment human tissue insight molecular phenotype nonhuman primate pain patient pain perception painful neuropathy ribosome profiling sex success tissue processing transcriptome transcriptome sequencing transcriptomics

项目摘要

Our collaborative groups, led by Drs. Price at UT Dallas (UTD), Dougherty at MD Anderson Cancer Center (MDACC) and Curatolo at University of Washington (UW), have been on the forefront of using human dorsal root ganglion (DRG) and other tissues to understand mechanisms that cause chronic pain in patients. Our work is on the leading edge of transcriptomic studies that have revealed unique features of the human DRG at the single neuron level. The goal of this project is to create the scientific foundation that will empower pain researchers around the world to approach the problem of treating pain in a new way, deeply rooted in a fundamental understanding of the first neurons and first synapses in the pain pathway. Our Center will focus on two prioritized aims. The first is identifying molecular phenotypes, using single cell and spatial transcriptomic technologies, of human sensory neurons from the DRG in organ donor recovered tissues and in patients suffering from chronic pain who are having surgeries where DRGs or peripheral nerves are removed. We will use this information to understand how nociceptors are activated in chronic pain disorders, with a focus on neuropathic pain, chronic neck pain and low back pain. These chronic pain disorders are the most disabling and the latter two are poorly modeled in animals. The second is to use spinal cord recovered from organ donors for single cell and spatial profiling with the goal of understanding the connectome of the human pain pathway at the first synapse. We will provide an integrated view of how nociceptors likely communicate with spinal cord neurons with the goal of understanding the pharmacology of projection neurons that send nociceptive signals to the brain to create pain perception. Our established collaboration and demonstrated track record of productivity ensures the success of this complex project. We envision creating actionable knowledge and data resources that can transform our understanding of human pain conditions leading to the generation of the treatments pain patients need.

我们的合作小组，由博士领导。 UT 达拉斯 (UTD) 的价格，MD 安德森癌症中心的多尔蒂 (MDACC) 和华盛顿大学 (UW) 的 Curatolo 一直处于使用人类背部的最前沿根神经节 (DRG) 和其他组织，以了解导致患者慢性疼痛的机制。我们的工作处于转录组学研究的前沿，这些研究揭示了人类 DRG 的独特特征单神经元水平。该项目的目标是建立增强疼痛的科学基础世界各地的研究人员正在以一种根深蒂固的新方式来解决治疗疼痛的问题对疼痛通路中第一个神经元和第一个突触的基本了解。我们中心将重点关注两个优先目标。第一个是使用单细胞和空间转录组学来识别分子表型技术，来自器官捐献者恢复的组织和患有疾病的患者的 DRG 的人类感觉神经元因慢性疼痛而接受背根神经节或周围神经切除手术的患者。我们将使用这个了解慢性疼痛疾病中伤害感受器如何被激活的信息，重点是神经性疼痛疼痛、慢性颈部疼痛和腰痛。这些慢性疼痛疾病是最严重的，后者是最严重的其中两个在动物身上的建模很差劲。第二种是利用从器官捐献者身上回收的脊髓进行单细胞和空间分析，目的是首先了解人类疼痛通路的连接组突触。我们将提供关于伤害感受器如何与脊髓神经元沟通的综合视图目的是了解向大脑发送伤害性信号的投射神经元的药理学创造疼痛感知。我们建立的合作关系和出色的生产力记录确保这个复杂项目的成功。我们设想创建可操作的知识和数据资源改变我们对人类疼痛状况的理解，从而产生治疗疼痛患者的方法需要。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

NaV1.7 mRNA and protein expression in putative projection neurons of the human spinal dorsal horn.

NaV1.7 mRNA 和蛋白质在人脊髓背角的假定投射神经元中的表达。

DOI：
10.1101/2023.02.04.527110
发表时间：
2023
期刊：
bioRxiv : the preprint server for biology
影响因子：
0
作者：
Shiers,Stephanie;Funk,Geoffrey;Cervantes,Anna;Horton,Peter;Dussor,Gregory;Hennen,Stephanie;Price,TheodoreJ
通讯作者：
Price,TheodoreJ

Neuroimmune Mechanisms Underlying Post-acute Sequelae of SARS-CoV-2 (PASC) Pain, Predictions from a Ligand-Receptor Interactome.

DOI：
10.1007/s11926-023-01107-8
发表时间：
2023-09
期刊：
Current rheumatology reports
影响因子：
5
作者：
Lesnak JB;Mazhar K;Price TJ
通讯作者：
Price TJ

Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons.

DOI：
10.1038/s41598-023-31603-x
发表时间：
2023-03-22
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
Shen, Breanna Q. Q.;Sankaranarayanan, Ishwarya;Price, Theodore J.;Tavares-Ferreira, Diana
通讯作者：
Tavares-Ferreira, Diana