BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 10115993
• 负责人: SUBBURAMAN MOHAN
• 金额: --
• 依托单位: VA LOMA LINDA HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2027-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10115993
• 关键词: Adult; Adverse effects; Affect; Age; Aging; Area; Ascorbic Acid; Ascorbic Acid Deficiency; Award; Bone Diseases; Bone Marrow; Book Chapters; Cartilage; Clinical; Collaborations; Complement Factor H; Degenerative polyarthritis; Development; Diagnosis; Drug Targeting; Elderly; Elements; Epigenetic Process; Event; Family; Financial Hardship; Fracture; Functional disorder; Funding; Future; General Population; Generations; Genes; Genetic Transcription; Goals; Health; Healthcare; Heterotopic Ossification; Hydroxylation; Hypoxia; Impairment; Injury; International; Knock-out; Laboratories; Lead; Life; Life Style; Mediating; Medical; Mentors; Metabolic Bone Diseases; Metabolism; Minerals; Mission; Molecular; Musculoskeletal; Musculoskeletal Diseases; Non-Insulin-Dependent Diabetes Mellitus; Nuclear; Obesity; Osteoclasts; Osteogenesis; Osteoporosis; Oxygen; Pathogenesis; Pathway interactions; Patients; Personal Satisfaction; Phosphotransferases; Population; Prevention strategy; Process; Procollagen-Proline Dioxygenase; Productivity; Promoter Regions; Proteins; Public Health; Publications; Publishing; Quality of life; Regulation; Research; Research Peer Review; Research Personnel; Research Priority; Role; Scientist; Seminal; Signal Pathway; Signal Transduction; Signaling Molecule; Skeletal system; Survivors; TBI Patients; TNFSF11 gene; Tertiary Protein Structure; Therapeutic; Thyroid Hormone Receptor Beta; Tight Junctions; Time; Tissues; Translational Research; Trauma; Traumatic Brain Injury; United States National Institutes of Health; Veterans; Wasting Syndrome; Woman; Work; age related; aged; base; bone; bone cell; bone loss; bone mass; bone metabolism; career; chronic pain; combat injury; combat zone; comorbidity; design; diabetic patient; effective therapy; functional status; health care delivery; high risk; hospitalization rates; improved; indexing; insight; meetings; member; men; mild traumatic brain injury; military service; military veteran; mortality; neurotransmission; new therapeutic target; notch protein; novel; novel therapeutic intervention; patient population; physically handicapped; prevent; programs; rehabilitation strategy; repaired; response; sensor; service member; skeletal abnormality; soft tissue; treatment strategy

SUMMARY This competitive renewal application of my SRCS program is focused on three major health problems in the VA patient population, TBI, osteoporosis and osteoarthritis. One of our major areas of focus is on the long- term negative impact of traumatic brain injury (TBI) on bone. TBI, a signature injury of combat operations, results in a myriad of clinical complications that have devastating effects on our battlefield warriors and represents one of CRADO’s five cross-cutting clinical priorities. In our studies, we have established that repetitive mild TBI exerts a significant negative impact on the skeletal system over the long term by influencing peak bone mass and by promoting ectopic bone formation in soft tissues after injury. Our current studies are focused on elucidating the key cellular elements and the relevant systemic and local signaling pathways that impact the development of ectopic bone in response to TBI and local trauma with a goal of developing novel therapeutic strategies for prevention and treatment of heterotopic ossification in TBI patients. The population of elderly veterans continues to increase, and, therefore, issues affecting the aged have become a VA research priority. Osteoporosis and osteoarthritis (OA) are significant age-related public health problems in the Veterans as well as in the general U.S. population and pose a substantial financial burden. It is estimated that approximately one in two women and one in four men age 50 and older will break a bone due to osteoporosis. OA is known to affect over 30 million adults in the U.S. The pathogenesis of osteoporosis and OA are known to involve increased destruction of bone and cartilage, not compensated by parallel increases in the synthesis of new tissue. Therefore, the long-term goals of my VA- and NIH-sponsored research is focused on identifying the defective signaling pathways that contribute to bone and cartilage loss in the elderly, and to develop novel anabolic strategies for treatment of these debilitating bone diseases. Our laboratory has been very productive over the years with 370 peer review research articles, 30 review articles and 28 book chapters. Our publications have received more than 45,000 citations with an H-factor of 89 and an i-10-index of 839. Our research has led to several important discoveries in the areas of bone and mineral metabolism and has received continuous funding from federal agencies (VA, NIH, DOD) over a span of 30 years. I was the recipient of the 2017 ASBMR Louis Avioli Founder’s award given in recognition of life-long contributions in translational research related to bone and mineral metabolism. Besides establishing strong active collaborations both locally and nationally, our program continues to successfully mentor a new generation of researchers and contributes to VA research administration at both a local and national level. Our ongoing studies are designed to not only provide mechanistic insights into the role of the key signaling pathways in the pathophysiology of the various bone-wasting diseases but also to identify novel and rational drug targets for the development of novel effective therapies to treat metabolic bone diseases that impact the health of veterans.

概括 我的SRCS计划的这种竞争性更新应用集中在三个主要健康问题上 VA患者人群，TBI，骨质疏松和骨关节炎。我们的主要关注领域之一是长期 创伤性脑损伤（TBI）对骨骼的负面影响。 TBI是战斗行动的签名伤害，结果 在无数的临床并发症中，对我们的战场勇士产生毁灭性影响，并代表一个 克拉多（Crado）的五个横切临床重点。在我们的研究中，我们确定了重复的轻度TBI 长期影响峰骨质量，长期对骨骼系统产生重大负面影响 并通过促进受伤后软时机中的生态骨形成。我们目前的研究集中于 阐明关键的细胞元素以及影响影响的系统和局部信号通路 响应TBI和局部创伤的生态骨骼的发展，目的是开发新的疗法 TBI患者预防和治疗异位骨化的策略。 老退伍军人的人口继续增加，因此，影响老年人的问题 成为VA研究的重点。骨质疏松症和骨关节炎（OA）是与年龄相关的重要公共卫生 退伍军人以及美国普通人口的问题，并构成了大量金融伯恩。这是 据估计，由于 骨质疏松症。已知OA在美国影响超过3000万成年人的骨质疏松和OA的发病机理 已知涉及增加骨骼和软骨的破坏，而不是通过平行增加而完成 新组织的合成。因此，我的VA和NIH赞助研究的长期目标集中在 确定有助于造成骨骼和软骨损失的有缺陷的信号通路，并 制定新的合成代谢策略来治疗这些使人衰弱的骨骼疾病。 多年来，我们的实验室非常有生产力，有370个同行评审研究文章，30条评论 文章和28章章节。我们的出版物收到了45,000多次引用，H因子为89 以及839的I-10索引。我们的研究导致了骨和小领域的一些重要发现 代谢，并在30年的时间内获得了联邦机构（VA，NIH，DOD）的持续资金。 我是获得终身捐款的2017年ASBMR Louis Avioli创始人奖的获得者 在与骨骼和矿物质代谢有关的翻译研究中。除了建立强大的活跃 在本地和全国范围内，我们的计划继续成功地为新一代而成为新一代的合作 研究人员并为当地和国家一级的VA研究管理局做出了贡献。我们正在进行的 研究旨在不仅为关键信号通路在 各种浪费骨疾病的病理生理学 开发新的有效疗法来治疗影响退伍军人健康的代谢骨疾病。