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.

提交此高级研究职业科学家申请是为了支持博士的研究。 理查德·利伯 (Richard L. Lieber) 之前在 VA 的支持下进行的研究已经阐明了这一点 用于肌腱的人体骨骼肌的解剖学和生物力学特性 转移手术用于脊髓损伤和中风患者的恢复。 受伤后丧失的功能通过手术转移到新的肌肉。 生物力学模型也用于开发定量。 允许外科医生选择最接近的剩余功能肌肉的指数 其结果是改善了患者的功能。 Lieber 团队还制定了手术后的客观标准。 开发了一种新颖的术中激光衍射装置，可以测量详细的、 该设备的工作原理是在手术过程中观察人体肌肉的微观特性。 激光与肌纤维内各向异性蛋白带之间的干扰 由于这些带的间距与肌肉力量、光学衍射有关。 从肌肉纤维中获取的信息可以以不损害肌肉的方式深入了解肌肉功能 这些研究不仅揭示了许多人类的正常工作范围。 肌肉，但它们已被用来发现以前未知的肌肉特性 中风、头部损伤、脊髓后可能发生的肌肉收缩。 受伤或肌肉萎缩症，可能会很痛苦，限制运动范围，而且很困难 利伯和同事测量的肌肉结构变化治疗费用昂贵。 表明“收缩的肌肉”在纵向生长的能力受到限制 方向（限制运动范围）和径向（限制强度）。 当这些研究人员最近揭示了这种生长限制的生物学基础 肌肉常驻干细胞数量急剧减少 挛缩，剩余的干细胞没有正常发育，而是保留在 这些观察结果为一条新的路线开辟了道路。 使用 FDA 批准的各种影响干细胞的药物进行研究，并可应用于新型药物 通过这种方式，可以实现从实验室到临床的快速转化。 综上所述，避免了与新药审批相关的许多监管障碍。 人体肌肉的解剖学、生物力学和生物学研究相结合 使我们的 VA 患者在手术和药物治疗方面受益，现在在 预计未来的支持将进行诊断和跟踪治疗干预。 随着退伍军人事务部对人类研究的投资产生可行的成果，继续保持这一轨迹 来治疗这些患者。