RR&D Senior Research Career Scientist Award Application

这份高级研究职业科学家申请书的提交是为了支持博士的研究。 理查德·L·利伯。之前在退伍军人事务部的支持下进行的研究已经阐明了 肌腱用人体骨骼肌的解剖学和生物力学特性 转院手术。这种手术是用于脊髓损伤和中风患者的恢复 受伤后丧失的功能。一块功能正常的肌肉通过手术转移到新的 失去功能的位置。生物力学建模也被用来开发定量 允许外科医生选择最接近的剩余功能肌肉的指数 已经丢失的那个人的生理特性。其结果是改善了患者的功能 术后选择手术入路的客观标准。利伯的团队也已经 开发了一种新型的术中激光衍射仪，它可以测量细节， 手术过程中人体肌肉的微观特性。该设备基于 激光与肌纤维内各向异性蛋白质带的干涉 他们自己。由于这些带的间距与肌力有关，所以光学衍射 从肌肉纤维提供对肌肉功能的洞察，而不会损害 纤维。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 在痉挛之后。肌肉痉挛，可能发生在中风、头部损伤、脊髓 损伤或肌营养不良，可能会疼痛，限制活动范围，并难以 治疗费用昂贵。利伯和他的同事测量的肌肉结构变化 表明“肌肉收缩”在纵向和纵向生长的能力有限。 方向(限制运动范围)和径向(限制强度)。洞察 这种生长受限的生物学基础最近被揭示出来，当时这些研究人员 证明了肌肉干细胞的数量在 痉挛，剩余的干细胞没有正常发育，而是保持在 不成熟，过度增殖的状态。这些观察结果开辟了一条新的道路 使用FDA批准的各种影响干细胞的药物进行的研究，可以应用于新的 患者群体。这样，从实验室到临床的快速转换可以通过以下方式实现 避免了与新药审批相关的许多监管障碍。总而言之， 人体肌肉的解剖学、生物力学和生物学研究相结合 使我们的退伍军人管理局患者在手术和医疗方面受益，现在在 进行诊断和跟踪治疗干预。未来的支持预计将 随着退伍军人管理局对人类研究的投资产生可操作的结果，继续这一轨迹 给治疗这些病人的临床医生。

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.