RR&D Senior Research Career Scientist Award Application

RR

• 批准号: 10531877
• 负责人: Richard L. Lieber
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-11-01 至 2026-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10531877
• 关键词: Address; Affect; Anatomy; Animal Model; Architecture; Articular Range of Motion; Atrophic; Award; Basic Science; Biological; Biological Models; Biomechanics; Cells; Cerebral Palsy; Chronic; Clinic; Clinical; Clinical Medicine; Clinical Trials; Contracture; Craniocerebral Trauma; Creativeness; Data; Defect; Development; Devices; Diagnosis; FDA approved; Fiber; Fibrosis; Functional disorder; Funding; Future; Grant; Growth; Hand; Human; Injury; Investments; Label; Laboratories; Lasers; Light; Malnutrition; Mammals; Measurement; Measures; Medical; Methodology; Methods; Microscopic; Molecular; Muscle; Muscle Fibers; Muscle function; Muscle satellite cell; Muscular Dystrophies; New Drug Approvals; Operating Rooms; Operative Surgical Procedures; Optics; Orthopedics; Outcome; Pain; Patients; Peripheral Nerves; Pharmaceutical Preparations; Physicians; Physiological; Positioning Attribute; Property; Proteins; Radial; Rana; Research; Research Personnel; Research Support; Science; Scientist; Secondary to; Series; Skeletal Muscle; Skin; Spinal cord injury; Stroke; Surgeon; Surgical Models; Tendon Transfer; Therapeutic Intervention; Time; Tissues; Translations; United States Department of Veterans Affairs; Upper Extremity; Work; base; biomechanical model; cancer cachexia; career; clinical translation; computerized; drug repurposing; frequency comb; functional restoration; grasp; improved; indexing; insight; muscle physiology; next generation; non-invasive system; nonhuman primate; novel; novel strategies; patient population; photonics; post stroke; prototype; rehabilitation research; skeletal muscle plasticity; stem cell population; stem cells; theories; tool; tool development

This Senior Research Career Scientist application is submitted to support the research of Dr. Richard L. Lieber. Previous research, performed under VA support, has elucidated the anatomical and biomechanical properties of human skeletal muscles that are used in tendon transfer surgery. This surgery is used for patients with spinal cord injury and strokes to restore function that has been lost after the injury. A functioning muscle is surgically moved to a new position where function was lost. Biomechanical modeling is also used to develop quantitative indices that allow surgeons to choose the remaining functioning muscle that is closest in physiological properties to the one that has been lost. The result is improved patient function after surgery and objective criteria for choice of surgical approach. Lieber’s group has also developed a novel, intraoperative laser diffraction device that can measure the detailed, microscopic properties of human muscles during surgery. This device works based on the interference between laser light and the anisotropic protein bands within the muscle fibers themselves. Since the spacing of these bands is related to muscle force, optical diffraction from muscle fibers provides insights into muscle function in a way that does not damage the fibers. These studies have not only revealed the normal operating range of many human muscles but they have been used to discover previously unknown muscle properties that occur after contracture. Muscle contractures, that may occur after stroke, head injury, spinal cord injury or muscular dystrophy, can be painful, limit range of motion and are difficult and expensive to treat. The muscle structural changes measured by Lieber and colleagues indicate that “contractured muscle” is limited in its ability to grow both in the longitudinal direction (limiting range of motion) and in the radial direction (limiting strength). Insights into the biological basis for this growth limitation was recently revealed when these investigators demonstrated that the muscle resident stem cell population was dramatically reduced in contractures and that the remaining stem cells did not develop normally but remained in an immature, hyperproliferative state. These observations have opened the way to a new line of research using various FDA-approved drugs that affect stem cells and can be applied to novel patient populations. In this way, rapid translation from laboratory to clinic can be made by avoiding the many regulatory hurdles associated with new drug approval. Taken together, the combination of anatomical, biomechanical and biological studies of human muscles has benefitted our VA patients both in terms of surgical and medical treatment and now in terms of making diagnoses and tracking therapeutic interventions. Future support is expected to continue this trajectory as the VA investment in human research yields actionable outcomes for clinicians treating these patients.

这高级研究职业科学家申请提交支持博士的研究。 Richard L.利伯在VA支持下进行的先前研究已经阐明了 用于肌腱的人体骨骼肌的解剖学和生物力学特性 转移手术该手术用于脊髓损伤和中风患者的恢复 受伤后失去的功能。一个功能正常的肌肉被手术转移到一个新的 失去功能的位置。生物力学建模也用于开发定量的 这些指数允许外科医生选择最接近的剩余功能肌肉， 生理特性与已经失去的特性的对比。结果是改善了患者的功能 术后并发症及手术入路选择的客观标准。Lieber的团队还 开发了一种新型的术中激光衍射装置， 在手术过程中人体肌肉的微观特性。该设备的工作原理是 激光与肌纤维内各向异性蛋白质条带之间的干涉 自己由于这些谱带的间距与肌肉力量有关， 从肌肉纤维提供了一种方式，不损害肌肉功能的见解。 纤维这些研究不仅揭示了许多人的正常操作范围， 肌肉，但他们已被用来发现以前未知的肌肉特性， 痉挛后。肌肉挛缩，可能发生在中风、头部损伤、脊髓损伤后 损伤或肌肉萎缩症可能是痛苦、限制运动范围的， Lieber及其同事测量的肌肉结构变化 这表明“收缩的肌肉”在其沿纵向和纵向生长的能力方面是有限的 方向（限制运动范围）和径向（限制强度）。洞察 这种生长限制的生物学基础最近被揭示出来， 研究表明，肌肉驻留干细胞数量在2008年显著减少， 痉挛，剩余的干细胞没有正常发育，而是保持在收缩状态 不成熟过度增殖状态这些观察结果开辟了一条新的路线， 研究使用各种FDA批准的药物，影响干细胞，并可应用于新的 患者人群。通过这种方式，可以通过以下方式实现从实验室到临床的快速转化： 避免了与新药批准相关的许多监管障碍。综合起来， 结合人体肌肉的解剖学、生物力学和生物学研究， 无论是在手术和医疗方面，还是现在在 进行诊断和跟踪治疗干预。预计未来的支持将 随着退伍军人事务部对人类研究的投资产生可操作的成果，继续这一轨迹 对于治疗这些患者的临床医生来说。