BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 10487703
• 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/10487703
• 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; Foxes; Functional disorder; Funding; Geroscience; Goals; Grant; Health; Health Sciences; Healthcare Systems; Heart; Holly; Immunotherapy; Impaired cognition; Incidence; Institution; Interneurons; Intervention; Knowledge; Laboratories; Lead; Leadership; Life; Link; Mentors; Microvascular Dysfunction; Modeling; Molecular; Molecular Abnormality; Mus; National Institute of Neurological Disorders and Stroke; Nature; Neurons; Neurosciences; Nitric Oxide Synthase; 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; base; 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; ranpirnase; 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 由于工作中暴露和流行病学因素。 Galvan 博士的研究目标是了解 导致 AD 的分子和生化变化，重点关注那些将衰老与 AD 联系起来的变化以及潜在的变化 其他痴呆症，并确定预防或治疗 AD 的干预措施。迄今为止，高龄是最大的风险 AD 因素。 Galvan 博士实验室的 VA Merit 资助项目 (1I01 BX002211-01A2) 重点关注使用 雷帕霉素是第一种经实验证明可以延缓小鼠衰老、治疗和/或阻止其进展的药物 广告。 Galvan 博士的优异资助工作促成了雷帕霉素治疗阿尔茨海默病的首次临床试验，并建立了 通过揭示血管对 AD 的影响的新机制，AD 血管病因学的一个新研究领域 认知障碍和痴呆（VCID），一个与退伍军人健康高度相关且特别令人感兴趣的领域 对于 NIA 和 NINDS。致病性 tau 蛋白与 AD 存在因果关系。基于致病性 tau 蛋白的证据 Galvan 博士的团队首次提供了 AD 大脑脉管系统中的积累，这是第二个 VA 优异资助的团队 Galvan 博士实验室的项目 (5 I01 BX002211-06) 将定义致病性 tau 诱导脑血管的机制 功能障碍。加尔万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疗法的靶向性 致病性 tau 蛋白，可以与最近获得 FDA 批准的针对淀粉样蛋白 - β 的免疫疗法相结合， 从而有效治疗AD。衰老过程中的分子损伤导致细胞衰老。衰老的星形胶质细胞 随衰老而积累，并在 AD 中显着增加。加尔文博士的实验室首次表明， 致病性 tau 蛋白进入星形胶质细胞，有效诱导细胞衰老。合作研究 Galvan 博士和 Holly Van Remmen 博士（OKC VA 医疗保健系统，VAHCS）的 (1RF1AG068283-01) 将 定义致病性 tau 诱导星形胶质细胞衰老的机制，了解其对 AD 病因学的贡献， 并测试杀死衰老细胞的药物和针对致病性 tau 蛋白的免疫疗法来治疗 AD。与她最近 搬到 OKC VAHSC 和附属机构俄克拉荷马大学健康科学中心 (OUHSC)，Dr. Galvan 扩大了与 Van Remmen 博士和 Arlan Richardson 博士（OKC VAHSC）研究了坏死性凋亡在衰老和 AD 中大脑细胞衰老激活中的作用。加尔文博士的 搬到 OKC VAHCS 促进了她与 Zoltan Ungvari 博士 (OUHSC) 在大脑方面的合作 AD 的微血管机制。资助 Galvan 博士与 Ungvari 博士以及外部人员的合作工作 研究人员 Viviana Perez 博士（俄勒冈州立大学，现在的 NIA）（1RF1AG057964）和 Rakez Kayed 博士（UTMB）首先提供了 致病性 tau 蛋白传递至脑血管内皮细胞、致病性 tau 蛋白在脑血管内积聚的证据 AD 中的内皮细胞和内皮细胞功能障碍和衰老。这些研究目前处于第二轮 Nature Communications 的评论表明，tau 免疫疗法可用于治疗血管性 tau 病 广告。 Galvan 博士是另外 2 项 NIH 资助项目（阿尔茨海默病协会/盖茨基金会资助项目）的联合研究员 以及迈克尔·J·福克斯基金会的资助。她担任老年科学和健康大脑中心的联合主任 OUHSC 的老龄化工作，并参与 NIH/NIA P30 俄克拉荷马州内森休克卓越中心的领导 OUHSC 和 OMRF 的衰老生物学 (NSC) 博士。她曾担任国家安全委员会的核心联合领导人和助理 她之前的附属机构 UT Health San 担任 NIA T32 衰老生物学培训项目主任 Antonio，以及她之前所在的南德克萨斯州 VAHCS 的 GRECC。 Galvan 博士荣获八项奖项， 美国老龄化协会主席，并担任《Geroscience》联合主编。她的工作已经 被引用超过 6,400 次，h-index=45。她曾在 VA BLRD NURD 和 NURC 审查小组中任职，并且是常务委员 NIH/CSR CMAD 研究部门成员。 Galvan 博士指导或指导了一名 CDA-2 实习生、4 名初级教师 和临床医生/科学家、4 名研究生或医学博士/博士生、2 名医学博士生研究员和 4 名博士后研究员 其他学员，其中大多数已经在科学和科学相关职业中取得了成功的职业生涯。