BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 10594023
• 负责人: Veronica Galvan
• 金额: --
• 依托单位: OKLAHOMA CITY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594023
• 关键词: Age; Aging; Agreement; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease model; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer' s disease therapy; American; Amyloid beta-Protein; Area; Astrocytes; Automobile Driving; Award; Biochemical; Biology of Aging; Blood Vessels; Blood flow; Brain; Cause of Death; Cell Aging; Cells; Cerebrovascular Disorders; Cities; Clinic; Clinical Trials; Collaborations; Communication; Communities; Dementia; Disease; Disease Progression; Elderly; Endothelial Cells; Epidemiologic Factors; Etiology; Excision; FDA approved; FRAP1 gene; Faculty; Foundations; Functional disorder; Funding; Geroscience; Goals; Grant; Health; Health Sciences; Healthcare Systems; Heart; Holly; Immunotherapy; Impaired cognition; Incidence; Institution; Interneurons; Intervention; Knowledge; Laboratories; Leadership; Life; Link; Medical Students; Mentors; Microvascular Dysfunction; Modeling; Molecular; Molecular Abnormality; Mus; National Institute of Neurological Disorders and Stroke; Nature; Neurons; Neurosciences; Nitric Oxide Synthase; NuRD complex; Oklahoma; Paper; Pathogenicity; Pathology; Pharmaceutical Preparations; Phase II Clinical Trials; Postdoctoral Fellow; Process; Public Health; Research; Research Personnel; Role; Safety; Science; Scientist; Seminal; Services; Shock; Sirolimus; South Texas; Students; Study Section; Tauopathies; Testing; Texas; Time; Toxic effect; Training Programs; Translating; United States Department of Veterans Affairs; United States National Institutes of Health; Universities; Veterans; Woman; Work; aging brain; attenuation; brain endothelial cell; career; cerebral microvasculature; dementia risk; design; doctoral student; drug testing; effective intervention; efficacy testing; high risk; human model; indexing; insight; interest; member; minority trainee; mouse model; novel; phase I trial; prevent; prion-like; programs; proteostasis; restoration; senescence; tau Proteins; tau aggregation; tau mutation; transmission process; undergraduate student; vascular cognitive impairment and dementia

Alzheimer's disease (AD) is a major public health concern. Veterans are at a higher risk for dementia late in life due to in-service exposures and epidemiological factors. The goal of Dr. Galvan’s research is to understand the molecular and biochemical alterations that cause AD, with a focus on those that link aging to AD and potentially other dementias, and to identify interventions to prevent or treat AD. Advanced age is, by far, the greatest risk factor for AD. A VA Merit-funded project (1I01 BX002211-01A2) in Dr. Galvan’s lab focused on the use of rapamycin, the first drug that was experimentally proven to slow aging in mice, to treat and/or block progression of AD. Dr. Galvan’s Merit-funded work led to the first clinical trial of rapamycin in Alzheimer’s disease and established a novel area of research in the vascular etiology of AD by revealing novel mechanisms of vascular contributions to cognitive impairment and dementia (VCID), an area of high relevance to Veterans’ health and of specific interest for NIA and NINDS. Pathogenic tau protein is causally implicated in AD. Based on evidence for pathogenic tau accumulation in vasculature of AD brain provided for the first time by Dr. Galvan’s team, a second VA Merit-funded project in Dr. Galvan’s lab (5 I01 BX002211-06) will define mechanisms of pathogenic tau-induced brain vascular dysfunction. Dr. Galvan’s studies are important for Veterans’ health because they will test immunotherapy targeting pathogenic tau, that can be combined with immunotherapy targeting amyloid-beta, recently approved by the FDA, to efficaciously treat AD. Molecular damage during aging leads to cellular senescence. Senescent astrocytes accumulate in aging and are markedly increased in AD. Dr. Galvan’s laboratory showed, for the first time, that pathogenic tau enters astrocytes, where it potently induces cellular senescence. Collaborative studies (1RF1AG068283-01) of Dr. Galvan and Dr. Holly Van Remmen (OKC VA Health Care System, VAHCS) will define mechanisms of pathogenic tau-induced astrocyte senescence, understand its contribution to AD etiology, and test drugs that kill senescent cells and immunotherapy targeting pathogenic tau to treat AD. With her recent move to OKC VAHSC and affiliated institution University of Oklahoma Health Sciences Center (OUHSC), Dr. Galvan expanded her established collaboration with Dr. Van Remmen and with Dr. Arlan Richardson (OKC VAHSC) on the role of necroptosis in the activation of cellular senescence in brain in aging and AD. Dr. Galvan’s move to OKC VAHCS promoted her established collaboration with Dr. Zoltan Ungvari (OUHSC) on brain microvascular mechanisms of AD. Funded collaborative work of Dr. Galvan with Dr. Ungvari and with external investigators Dr. Viviana Perez (OSU, now NIA) (1RF1AG057964) and Dr. Rakez Kayed (UTMB) provided first evidence for pathogenic tau transmission to brain vascular endothelial cells, accumulation of pathogenic tau in endothelial cells and endothelial cell dysfunction and senescence in AD. These studies, currently in 2nd round of review in Nature Communications, showed that tau immunotherapy may be used to treat vascular tauopathy in AD. Dr. Galvan is co-Investigator in 2 additional NIH grants, an Alzheimer’s Association/Gates Foundation grant and a Michael J. Fox Foundation grant. She serves as co-Director of the Center for Geroscience and Healthy Brain Aging at OUHSC, and is involved in leadership of the NIH/NIA P30 Oklahoma Nathan Shock Center of Excellence in the Biology of Aging (NSC) at OUHSC and OMRF. She served as Core Co-Leader in the NSC and as Associate Director of the NIA T32 Training Program in the Biology of Aging at her prior affiliated institution, UT Health San Antonio, and in the GRECC at her prior station, South Texas VAHCS. Dr. Galvan has received eight awards, is President of the American Aging Association, and serves as Co Editor-in-Chief of Geroscience. Her work has been cited over 6,400 times with h-index=45. She served in VA BLRD NURD and NURC review panels and is a standing member in the NIH/CSR CMAD Study Section. Dr. Galvan mentors or mentored a CDA-2 trainee, 4 junior faculty and clinician/scientists, 4 graduate or MD/PhD students, 2 MD student fellows, and 4 postdoctoral fellows among other trainees, most of which have gone on to successful careers in science and science-related professions.

阿尔茨海默病(AD)是一个主要的公共卫生问题。退伍军人晚年患痴呆症的风险更高 由于在职接触和流行病学因素。加尔文博士的研究目标是了解 引起阿尔茨海默病的分子和生化变化，重点是那些将衰老与阿尔茨海默病联系起来的变化，并可能 其他痴呆症，并确定预防或治疗阿尔茨海默病的干预措施。到目前为止，高龄是最大的风险 AD的因素。退伍军人管理局功勋资助的项目(1I01 BX002211-01A2)在Galvan博士的实验室中专注于使用 雷帕霉素是第一种被实验证明可以延缓小鼠衰老的药物，用于治疗和/或阻止糖尿病的进展 广告。Galvan博士的功绩资助的工作导致了雷帕霉素在阿尔茨海默病中的第一次临床试验，并建立了 揭示血管参与阿尔茨海默病的新机制是AD血管病因学研究的新领域 认知障碍和痴呆症(VCID)，一个与退伍军人健康高度相关和特别感兴趣的领域 用于NIA和NINDS。致病tau蛋白与阿尔茨海默病密切相关。基于致病牛磺酸的证据 Galvan博士的团队首次提供了AD大脑血管系统的积聚，这是由VA Merit资助的第二个 Galvan博士实验室的项目(5 I01 BX002211-06)将定义tau诱发脑血管的致病机制 功能障碍。加尔文博士的研究对退伍军人的健康很重要，因为他们将测试免疫治疗的靶向性 致病性tau，可以与最近FDA批准的针对淀粉样β蛋白的免疫疗法相结合， 有效治疗阿尔茨海默病。衰老过程中的分子损伤会导致细胞衰老。衰老的星形胶质细胞 随着年龄的增长而积累，并在AD时显著增加。加尔文博士的实验室第一次表明， 致病tau进入星形胶质细胞，在那里它有效地诱导细胞衰老。合作研究 (1RF1AG068283-01)Galvan博士和Holly Van Remman博士(OKC VA Health Care System，VAHCS)将 明确病理性tau诱导星形胶质细胞衰老的机制，了解其在AD病因中的作用， 并测试杀死衰老细胞的药物和针对致病tau的免疫疗法来治疗AD。随着她最近的 搬到俄克拉何马大学VAHSC及其附属机构俄克拉荷马大学健康科学中心(OUHSC)，Dr。 Galvan扩大了她与Van Remman博士和Arlan Richardson博士(OKC)的合作 VAHSC)关于坏死下垂在衰老和AD中激活脑细胞衰老中的作用。加尔文医生的 转到OKC VAHCS促进了她与Zoltan Ungvari博士(OUHSC)在大脑方面的既定合作 阿尔茨海默病的微血管机制。资助Galvan博士与Ungvari博士和外部机构的协作工作 研究人员Viviana Perez博士(俄亥俄州立大学，现为NIA)(1RF1AG057964)和Rakez Kayed博士(UTMB)首先提供 致病tau向脑血管内皮细胞传播的证据，致病tau在脑血管内皮细胞中的积累 阿尔茨海默病中内皮细胞和内皮细胞功能障碍及衰老。这些研究目前处于第二轮 发表在《自然通讯》杂志上的综述显示，tau免疫疗法可用于治疗血管紧张性疾病。 广告。加尔文博士是NIH另外两笔赠款的联合研究员，这两笔赠款是阿尔茨海默氏症协会/盖茨基金会的赠款 以及迈克尔·J·福克斯基金会的拨款。她是老年科学和健康大脑中心的联席主任 在OUHSC老化，并参与领导NIH/NIA P30俄克拉荷马州内森休克卓越中心 在OUHSC和OMRF的衰老生物学(NSC)。她曾担任国家安全委员会的核心联合领导人和助理 NIA T32衰老生物学培训项目主任，在她之前的附属机构UT Health San 安东尼奥，并在她的前一站，南得克萨斯州VAHCS的GRECC。加尔文博士已经获得了八个奖项， 美国老龄化协会主席，并担任Geroscience的联合主编。她的工作一直是 被引用6400多次，h-index=45。她曾在退伍军人事务部、BLRD、NuRD和NURC审查小组任职，是一名常设 NIH/CSR CMAD研究组成员。加尔文博士指导或指导了一名CDA-2学员，4名初级教员 和临床医生/科学家，4名研究生或医学博士研究生，2名医学博士研究生，4名博士后研究员 其他受训人员，其中大多数人在科学和与科学相关的职业中取得了成功。