Administrative Supplement to existing K08 award - K08DK120934-01-04 Van Batavia J - Role of CRH-neurons BN/Uncovering Heterogeneity of BN

现有 K08 奖项的行政补充 - K08DK120934-01-04 Van Batavia J - CRH 神经元 BN 的作用/揭示 BN 的异质性

• 批准号: 10629808
• 负责人: Jason Philip Van Batavia
• 金额: $ 9.6万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10629808
• 关键词: Administrative Supplement; Adult; Advisory Committees; Affect; Award; Basic Science; Bioinformatics; Biological Process; Bladder; Bladder Control; Brain; Brain Stem; Cell Nucleus; Child; Childhood; Chronic; Clinical; Clinical Sciences; Corticotropin-Releasing Hormone; Disease; Ensure; Environment; Fiber; Foundations; Future; Genomics; Goals; Grant; Heterogeneity; International; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Long-Term Effects; Mentors; Mus; Nerve; Neurons; Neurosciences; Patients; Pattern; Pediatric Hospitals; Pennsylvania; Philadelphia; Photometry; Pontine structure; Population Control; Prevalence; Research; Research Training; Resources; Role; School-Age Population; Scientist; Surgeon; Techniques; Therapeutic; Time; Training; Translating; Universities; Urination; Urine; Urologist; Urology; Vocational Guidance; Volition; career development; experience; lower urinary tract symptoms; mid-career faculty; mind control; mouse model; new therapeutic target; novel; prevent; single-cell RNA sequencing

PROJECT SUMMARY/ABSTRACT The candidate for this K08 Mentored Clinical Scientist Research Career Development Award aims to become an expert and leader in the field of neuro-urology, specifically on furthering our understanding of the brain-bladder control of volitional voiding. Lower urinary tract symptoms (LUTS) and disorders of voiding are among the most common reasons for referral to the urologist and affect ~20% of school-aged children and >40% of adults over 40 years old. Despite this prevalence, the specific neuronal populations that control voiding remain largely unknown which limits therapeutic options. Recent advances in neuroscience, genomics and bioinformatics will now allow study of specific neuronal subpopulations and characterization of the cellular heterogeneity inherent to all brain and brainstem nuclei. The proposed research in this grant will be performed in primary mentor Dr. Steven Zderic’s laboratory using mice. Aim 1 will determine the effects of long-term activation of one specific neuronal subpopulation in the pontine micturition center (i.e., Barrington’s nucleus, BN) on voiding function. These specific neurons express corticotropin-releasing hormone (CRH) and these neurons in preliminary studies were shown to inhibit voiding, thus activation of these neurons is expected to cause infrequent voiding and lead to bladder wall remodeling from chronic holding of urine. Aim 2 will identify the time and temporal pattern of firing of these CRH-expressing BN neurons in relation to volitional voiding using fiber photometry in freely moving mice. Aim 3 will utilize single cell RNA-sequencing techniques to identify and characterize the neuronal subpopulations that reside in and around BN. The first two aims will help define the role of BN CRH-neurons and potentially create a novel murine model of bladder wall remodeling, while aim 3 will lead to the identification of novel neuronal subpopulations for future study which could potentially lead to new therapeutic targets for LUTS and voiding disorders. The candidate brings to this proposal his experience studying voiding disorders both from a clinical and basic science standpoint. This career development proposal aims to provide the candidate with required additional training that leverages the resource-rich environment of the Children’s Hospital of Philadelphia and University of Pennsylvania. The candidate will be guided by an experienced mentoring team at CHOP [Dr. Zderic – Direct of Pediatric Urology Research; Dr. Seema Bhatnager – Associate Professor, neuroscientist; and Dr. Deanne Taylor – Director of Bioinformatics]. An Advisory Committee of internationally recognized leaders will provide content expertise and career counseling to ensure the candidate has a successful transition to independence as a surgeon-scientist. All together this research and training plan will provide the candidate with a foundation in advanced neuroscience, genomic, and bioinformatics necessary for achieving his long-term goals of understanding how specific brain and brainstem neuronal populations control voiding and finding ways to translate this knowledge into clinical improvement for patients with LUTS and voiding disorders.

项目总结/摘要 K 08指导临床科学家研究职业发展奖的候选人旨在成为 神经泌尿学领域的专家和领导者，特别是在促进我们对脑膀胱的理解方面 控制意志排泄。下尿路症状（LUTS）和排尿障碍是最常见的 转诊至泌尿科医生的常见原因，影响约20%的学龄儿童和>40%的成年人 40岁尽管如此，控制排尿的特定神经元群体在很大程度上仍然存在 这限制了治疗选择。神经科学、基因组学和生物信息学的最新进展将 现在允许研究特定的神经元亚群和表征固有的细胞异质性 所有的脑和脑干细胞核。在这项补助金的拟议研究将在主要导师博士进行。 史蒂文·兹德里克的实验室用老鼠做实验。目的1将确定长期激活一种特定的 脑桥排尿中心的神经元亚群（即，Barrington's nucleus，BN）对排尿功能的影响。 这些特定的神经元表达促肾上腺皮质激素释放激素（CRH），这些神经元在初步研究中 显示抑制排尿，因此这些神经元的激活预计会导致排尿不频繁， 长期憋尿导致的膀胱壁重塑目标2将确定 在自由运动中，使用纤维光度法，这些表达CRH的BN神经元的放电与自愿排尿有关。 小鼠目的3将利用单细胞RNA测序技术来鉴定和表征神经元 居住在BN及其周围的亚群。前两个目标将有助于确定BN CRH神经元的作用 并有可能建立一种新的膀胱壁重塑的小鼠模型，而aim 3将导致识别 新的神经元亚群的未来研究，这可能会导致新的治疗靶点， LUTS和排尿障碍。候选人将他研究排尿障碍的经验带到这个提案中 从临床和基础科学的角度来看。本职业发展建议旨在提供 候选人需要额外的培训，利用儿童医院资源丰富的环境 费城和宾夕法尼亚大学。候选人将由一个经验丰富的辅导团队指导 在CHOP [Zderic博士-儿科泌尿学研究指导; Seema Bhatnager博士-副教授， 神经科学家;和Deanne Taylor博士-生物信息学主任]。国际咨询委员会 公认的领导者将提供内容专业知识和职业咨询，以确保候选人有一个成功的 作为一名外科医生兼科学家的独立性。所有这些研究和培训计划将提供 候选人在先进的神经科学，基因组学和生物信息学的基础上实现他的目标所必需的 长期目标是了解特定的大脑和脑干神经元群体如何控制排尿， 寻找将这些知识转化为临床改善的方法，以改善下尿路症状和排尿障碍患者的情况。

项目成果

Single institution experience with telemedicine for pediatric urology outpatient visits: Adapting to COVID-19 restrictions, patient satisfaction, and future utilization.

• DOI: 10.1016/j.jpurol.2021.05.012
• 发表时间: 2021-08
• 期刊: Journal of pediatric urology
• 影响因子: 2
• 作者: Gan Z;Lee SY;Weiss DA;Van Batavia J;Siu S;Frazier J;Zderic SA;Shukla AR;Srinivasan AK;Kolon TF;Zaontz MR;Canning DA;Long CJ
• 通讯作者: Long CJ

Potential benefits of functional magnetic resonance urography (fMRU) over MAG3 renal scan in children with obstructive uropathy.

• DOI: 10.1016/j.jpurol.2021.07.005
• 发表时间: 2021-10
• 期刊: Journal of pediatric urology
• 影响因子: 2
• 作者: Viteri B;Calle-Toro JS;Ballester L;Darge K;Furth S;Khrichenko D;Van Batavia J;Otero H
• 通讯作者: Otero H