BLRD Research Career Scientist Award Application

阿尔茨海默病（AD）是一个主要的公共卫生问题。退伍军人在晚年患痴呆症的风险更高 由于在职暴露和流行病学因素。加尔文博士研究的目的是了解 导致AD的分子和生物化学改变，重点是那些将衰老与AD联系起来的改变， 其他痴呆症，并确定干预措施，以预防或治疗AD。到目前为止，高龄是最大的风险， AD的因素。Galvan博士实验室的VA Merit资助项目（1 I 01 BX 002211 - 01 A2）重点关注使用 雷帕霉素是第一种被实验证明可以延缓小鼠衰老的药物， AD. Galvan博士的Merit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 一个新的研究领域，在血管病因学的AD，揭示了新的机制，血管的贡献， 认知障碍和痴呆症（VCID），这是一个与退伍军人健康高度相关的领域， 对于NIA和NINDS。致病性tau蛋白与AD有因果关系。基于致病性tau蛋白的证据 Galvan博士的团队首次提供了AD脑血管系统中的累积，这是第二个VA Merit资助的研究。 Galvan博士实验室的一个项目（5 I 01 BX 002211 -06）将定义致病性tau诱导的脑血管疾病的机制。 功能障碍Galvan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作用。 致病性tau，可以与靶向淀粉样蛋白β的免疫疗法联合使用，最近获得FDA批准， 有效治疗AD。衰老过程中的分子损伤导致细胞衰老。衰老星形胶质细胞 在衰老中积累，在AD中显著增加。加尔文博士的实验室首次表明， 致病性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 Galvan博士和冬青博士货车Remmen（OKC VA医疗保健系统，VAHCS）的（1 RF 1AG 068283 -01）将 定义致病性tau诱导的星形胶质细胞衰老的机制，了解其对AD病因的贡献， 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。随着她最近 搬到俄克拉荷马大学VAHSC和附属机构俄克拉荷马州健康科学中心（OUHSC），博士。 Gal货车扩大了她与货车Remmen博士和Arlan Richardson博士（OKC）的合作 VAHSC）对衰老和AD中坏死性凋亡在脑细胞衰老激活中的作用的研究。加尔文医生 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博士和外部 研究人员Viviana Perez博士（俄勒冈州立大学，现为NIA）（1 RF 1AG 057964）和Rakez Kayed博士（UTMB）首先提供了 致病性tau蛋白传递到脑血管内皮细胞的证据， 内皮细胞和内皮细胞功能障碍和衰老。这些研究，目前在第二轮 发表在《自然通讯》杂志上的一篇综述显示，tau免疫疗法可用于治疗血管性tau蛋白病， AD. Galvan博士是另外两项NIH赠款的共同研究者，这两项资助是阿尔茨海默氏症协会/盖茨基金会的资助。 以及迈克尔·J·福克斯基金会的资助她是老年科学和健康大脑中心的联合主任。 OUHSC的老龄化，并参与领导NIH/NIA P30俄克拉荷马州内森休克卓越中心 在老化生物学（NSC）在OUHSC和OMRF。她曾担任国家安全委员会的核心联合领导人， NIA T32老化生物学培训计划主任，她以前的附属机构，UT Health San 安东尼奥，并在GRECC在她的前站，南得克萨斯州VAHCS。Galvan博士获得了八个奖项， 美国老龄化协会主席，并担任Geroscience的联合主编。她的作品曾 被引用超过6,400次，h指数=45。她曾在VA BLRD和CADC审查小组任职，是一名常设 NIH/CSR CMAD研究组成员。Galvan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/博士生，2名医学博士研究生和4名博士后研究员，其中 其他受训人员，其中大多数已在科学和与科学有关的职业中取得成功。

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.