Biomolecular and Cellular Mechanisms of Diabetic Skeletal Fragility

项目摘要/摘要 该提案包括一项补充研究计划，以便顺利完成PI的原始 5年期K01项目。该专业人士现为香港中文大学生物工程系助理教授。 马萨诸塞大学达特茅斯分校高级研究中心正式研究合作者 贝丝以色列女执事医疗中心的矫形外科研究(CAOS)。她得到了她的大力支持 机构，并将75%的精力投入到这个项目中。PI有导师和合作者，他们拥有广泛的 帮助她开展工作并在这个项目期间提供职业指导的专业知识。她的导师和 合作者在生物力学、糖尿病临床问题、细胞和组织培养方法、高 分辨率成像和分子生物学技术。这个项目的重点是骨骼脆性的原因 2型糖尿病，这在很大程度上是未知的。晚期糖基化积累导致的骨基质缺陷 最终产品和/或微体系结构被认为是潜在的机制。的总目标是 该项目旨在确定糖尿病骨骼脆性的潜在生物分子和细胞机制。 在这6个月的补充期间，特别关注成功完成她最初的两个目标。这些 两个目标是：a)确定晚期糖基化终末产物、微损伤和皮质 孔隙度对糖尿病骨骼脆性的影响，以及B)以确定高血糖和非酶糖基化的影响 对骨细胞活性的影响。应聘者已经接受了几项全新技能的培训，包括测量 基因表达、细胞和组织培养方法以及其他与分子生物学相关的技术 她最初获得的K01项目。这项K01补充建议将为她提供额外的时间和 成功实现这些目标所需的资源(由于新冠肺炎大流行相关研究障碍而需要) 目标。

Project Summary/Abstract This proposal includes a supplementary research plan that allows for successful completion of the PI’s original 5-year K01 project. The PI is currently an Assistant Professor in the Department of Bioengineering at the University of Massachusetts Dartmouth and a formal Research Collaborator at the Center for Advanced Orthopaedic Studies (CAOS) at Beth Israel Deaconess Medical Center (BIDMC). She is well supported by her institution and devotes 75% effort to this project. The PI has mentors and collaborators with a wide array of expertise to help her conduct her work and offer career guidance during this project. Her mentors and collaborators have expertise in biomechanics, clinical issues in diabetes, cell and tissue culture methods, high- resolution imaging, and molecular biology techniques. This project focuses on the causes of skeletal fragility in type 2 diabetes, which are largely unknown. Deficits in bone matrix via the accumulation of advanced glycation end-products and/or microarchitecture have been suggested to be potential mechanisms. The overall goal of this project is to determine the underlying biomolecular and cellular mechanisms of diabetic skeletal fragility with a specific focus during this supplemental 6-month period to successfully complete two of her original aims. These two aims are: A) to determine the contribution of advanced glycation end-products, microdamage, and cortical porosity to diabetic skeletal fragility, and B) to determine the effect of hyperglycemia and non-enzymatic glycation on osteocyte activity. The candidate has already trained in several brand-new skills including measurement of gene expression, cell and tissue culture methods, and other molecular biology related technologies as part of her originally awarded K01 project. This K01 supplemental proposal will provide her with additional time and resources (needed due to COVID-19 pandemic-related research hindrances) to successfully achieve these goals.