NIMHD Adjunct Investigator Program

NIMHD 兼职研究员计划

• 批准号: 10706232
• 负责人: Anna Maria Napoles
• 金额: $ 44.52万
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706232
• 关键词: Address; Admixture; Adult; Affect; African; African American; African American population; African ancestry; Aging; Air Pollution; Amphotericin B; Appointment; Area; Biological; Black Populations; Blood Pressure; Body mass index; Breast Cancer Cell; Cancer Biology; Carbon Black; Cardiovascular Diseases; Cardiovascular system; Categories; Cell Proliferation; Clinic; Clinical Investigator; Clinical Research; Cohort Studies; Collaborations; Communities; County; Cross-Sectional Studies; DNA Damage; DNA Methylation; DNA Repair; DNA Repair Disorder; Data; Detection; Development; Diabetes Mellitus; Diabetes prevention; Discrimination; Economic Factors; Enrollment; Environment; Environmental Risk Factor; Ethnic Origin; Fetal Growth; Food; Funding; Genes; Genetic; Genetic Transcription; Genotype; Glycosylated hemoglobin A; Goals; Health; Health Disparities Research; Heart Diseases; High Prevalence; High Risk Woman; Hispanic Populations; Home; Hyperglycemia; Hypertension; Immigrant; Individual; Intervention; Knowledge; Laboratories; Life Cycle Stages; Link; Longevity; Malignant Neoplasms; Mammary Neoplasms; Maternal Age; Mentors; Mesenchymal Stem Cells; Methylation; Modeling; Molecular Profiling; Monitor; Morbidity - disease rate; Mutation; National Heart, Lung, and Blood Institute; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; National Institute of Child Health and Human Development; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Environmental Health Sciences; National Institute on Minority Health and Health Disparities; Neighborhoods; Neoplasm Metastasis; Nitrogen Dioxide; Obstructive Sleep Apnea; Paper; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phenotype; Physical environment; Physicians; Play; Pollution; Population; Postdoctoral Fellow; Predisposition; Prevention; Psychosocial Factor; Publishing; Race; Research; Research Personnel; Resolution; Risk; Risk Factors; Role; San Francisco; Scleroderma; Seasons; Severities; Sleep; Social Environment; South African; Strategic Planning; Stress; Systemic Scleroderma; Therapeutic; Time; Toxicology; Training; Tumor Biology; Underrepresented Minority; United States National Institutes of Health; Variant; Washington; Work; ambient air pollution; base; cardiometabolism; cardiovascular disorder risk; cardiovascular risk factor; career; cognitive performance; cohort; disparity reduction; diversity and inclusion; epigenome; ethnic diversity; exome sequencing; experience; fetal; frailty; gene environment interaction; genome wide association study; gestational weight gain; glycosylated serum albumin; health disparity; healthy aging; heart function; improved; inhibitor; insight; interest; malignant breast neoplasm; maternal depression; metabolome; microbiome; middle age; minority health disparity; mortality; nocturnal Hypoxemia; novel; parity; pollutant; prenatal; prevent; programs; racial and ethnic; racial and ethnic disparities; racial disparity; response; screening; sex; sleep health; sleep quality; social determinants; social factors; social health determinants; socioeconomic disparity; spatiotemporal; stem-like cell; supportive environment; tenure track; therapeutic target; transcriptome; tumor; ultrafine particle

In FY22, we continued to fund 8 Adjunct Investigators to conduct health disparities research and mentor racially-ethnically diverse trainees in their labs. Three investigators are Senior Investigators who have been champions in diversity and inclusion. Of the other 5, one is an Assistant Clinical Investigator, and the others are Tenure-Track Investigators (TTIs). This strategy of funding seasoned health disparities investigators and early career investigators has been exceptionally helpful in creating opportunities and supportive environments for trainees. Stefan Ambs, NCI In FY22, Dr. Ambs and his trainee completed a study of the influence of diabetes on breast cancer biology that aimed to identify shared phenotypes and molecular signatures by investigating the metabolome, transcriptome, and tumor mutational burden. Diabetes did not enhance cell proliferation but induced mesenchymal and stem cell-like phenotypes linked to increased mobility and odds of metastasis. It also promoted oxyradical formation and both transcriptome and mutational signatures of DNA repair deficiency. Moreover, food- and microbiome-derived metabolites tended to accumulate in breast tumors in presence of diabetes, potentially affecting tumor biology. Breast cancer cells cultured under hyperglycemia acquired increased DNA damage and sensitivity to DNA repair inhibitors. Diabetes-associated breast tumors may show an increased drug response to DNA damage repair inhibitors that are cancer therapeutics and could help reduce racial disparities in breast cancer mortality. Fasil Tekola-Ayele, NICHD Dr. Tekola-Ayeles research focuses on two themes at the maternal-placental-fetal interface genetics of fetal growth and placental epigenome/transcriptome. His study revealed that gene-environment interactions account for the majority of variation in placental DNA methylation. Methylation at 70% of variable methylated regions (VMRs), which are regions in the epigenome with high inter-individual methylation variability, was best explained by Gene Environment, followed by genotype only (17.7%), and Gene + Environment (12.3%). Prenatal environment alone best explained only 0.03% of VMRs. They observed that 95.4% of G E models and 93.9% of G + E models included maternal age, parity, delivery mode, maternal depression or gestational weight gain. Michele Evans, NIA Using the Healthy Aging in Neighborhoods of Diversity across the Life Span Study (HANDLS-PI Dr. Evans) she published three papers with her post-doctoral fellow related to biologic pathways underlying frailty development in middle-aged adults, the roles of race and social determinants of health in and an accelerated aging phenotypte, and the relationship of APOE gene region methylation with cognitive performance. Her work has found novel and significant sex-specific transcriptional changes that occur in middle-aged frailty, enhancing knowledge on frailty progression and potential therapeutic targets to prevent frailty and reduce disparities. Pravitt Gourh, NIAMS Dr. Gourh has the largest cohort (n=1300) of African American scleroderma patients. The goal is to study scleroderma (systemic sclerosis, SSc) in the African American (AA) population, (i) to identify genes that increase SSc susceptibility, and (ii) to understand the basic mechanisms by which these genes cause SSc. Genome wide association study and exome sequencing have led to identification of HLA and non-HLA genes increasing SSc susceptibility in the AA population. He is expanding his work in this area to include social determinants of health (SDoH) because their interactions with genetic factors, including genetic admixture, could help explain the higher prevalence and severity of scleroderma in African American patients. Chandra Jackson, NIEHS Dr. Jacksons research group is investigating how physical and social environments impact racial-ethnic and socioeconomic disparities in cardiometabolic health, with a particular interest in the influence of sleep health. She published work that indicates that among African American adults, there is a longitudinal association between increasing (vs. stable) discrimination and decreased sleep quality. In cross-sectional analyses, higher discrimination was associated with shorter sleep duration, independent of stress. In a study of obstructive sleep apnea (OSA) and nighttime blood pressure among African Americans, she found that OSA and nocturnal hypoxemia were associated with high nighttime blood pressure, which could help explain racial disparities in hypertension. With her post-doctoral fellow (funded by NIMHD DIR), she published an article addressing subclinical racial-ethnic disparities in sleep-related cardiac function that expands scientific approaches by including modifiable physical and social environments over the life-course to identify points of intervention for primordial prevention. Tiffany Powell Wiley, NHLBI The Powell-Wiley laboratory has continued to explore racial-ethnic disparities in cardiovascular risk factors and health among African American women at high risk. She is leading a collaborative effort to establish a community-based cardiovascular screening clinic in a primarily African American neighborhood in Washington, D.C. to enroll more African Americans in clinical research to address disparities. She published an extremely useful framework demonstrating the links (mechanisms) between social determinants of health (SDoH), which encompass the economic, social, environmental, and psychosocial factors that influence health, and the significant role they play in the development of cardiovascular disease (CVD) risk factors as well as CVD morbidity and mortality. Anne E. Sumner, MD, NIDDK Dr. Sumners work has focused on (a) improving the detection and prevention of diabetes and its complications in people of African descent; (b) identifying the social determinants of diabetes and heart disease and (c) training African physicians as well as under-represented minorities to be clinical investigators. Dr. Sumner and her trainees have been working to analyze data from Dr. Sumners Diabetes and Heart Disease in Blacks observational cohort study. As of August 2022, she had enrolled 934 Blacks in the cohort, specifically 229 African American and 605 African immigrant adults. In addition, she published a recent study that assessed 1,274 South Africans living in Cape Town to examine it combining HbA1c with glycated albumin (GA) could improve detection of dysglycaemia. They demonstrated for the first time in an African population the existence of both the positive correlation between body mass index (BMI) and HbA1c and the negative correlation between BMI and GA. Hence, combining these two non-fasting markers of glycemia improves detection of dysglycaemia across BMI categories. Kyle Messier, NIEHS Dr. Kyle Messiers lab has two overarching themes: (1) geospatial exposure, disparity, and risk mapping; and (2) Spatiotemporal mapping connections to toxicology. He published an analysis that systematically compared urban variation at several scales, from hyperlocal (<100 m) to regional (>10 km), and assessed consequences for outdoor air pollution experienced by residents of different races and ethnicities, by creating a set of uniquely extensive and high-resolution observations of spatially variable pollutants: NO, NO2, black carbon (BC), and ultrafine particles (UFP). Through full coverage monitoring in four San Francisco Bay Area counties, they found that median concentrations of UFP, NO, and NO2 are, for Hispanic and Black populations, 8 to 30% higher than the population average. Their results illustrate how detailed and extensive fine-scale pollution observations can add new insights about disparities in air pollution exposures at the population scale.

在22财年，我们继续为8名兼职研究人员提供资金，以在实验室中进行健康差异研究和导师的种族多样化的学员。三名调查人员是曾担任多样性和包容性冠军的高级调查员。在其他5个中，一个是助理临床研究者，而另一位是终身轨调查人员（TTIS）。这项资助经验丰富的健康差异调查人员和早期职业调查人员的策略非常有助于为受训者创造机会和支持环境。 Stefan Ambs，NCI 在22财年，AMBS和他的实习生完成了一项研究糖尿病对乳腺癌生物学的影响的研究，旨在通过研究代谢组，转录组和肿瘤突变负担来鉴定共享的表型和分子特征。糖尿病不会增强细胞增殖，而是诱导的间充质和类似干细胞的表型，与转移的迁移率和赔率增加有关。它还促进了DNA修复缺乏的转录组和突变特征。此外，食物组和微生物组衍生的代谢产物倾向于在存在糖尿病的情况下积聚在乳腺肿瘤中，可能会影响肿瘤生物学。在高血糖中培养的乳腺癌细胞获得了DNA损伤和对DNA修复抑制剂的敏感性。糖尿病相关的乳腺肿瘤可能显示出对DNA损伤修复抑制剂的药物反应增加，这些抑制剂是癌症治疗剂，可以帮助降低乳腺癌死亡率的种族差异。 Fasil Tekola-Ayele，Nichd Tekola-Ayeles博士的研究重点是胎儿生长和胎盘表观基因组/转录组的母体植物界界面遗传学的两个主题。他的研究表明，基因环境相互作用占胎盘DNA甲基化的大部分变化。在70％的可变甲基化区域（VMR）的甲基化是具有高个体间甲基化变异性的表观基因组中的区域，最好用基因环境来解释，其次是基因型（17.7％）和基因 +环境（12.3％）。仅凭产前环境最好仅解释了0.03％的VMR。他们观察到95.4％的G E模型和93.9％的G + E模型包括孕妇年龄，平等，输送模式，母体抑郁或妊娠体重增加。 米歇尔·埃文斯（Nia） 在整个生命跨度研究（Handls-Pi Evans博士）中，她在多样性的社区中使用健康的衰老，她发表了三篇论文，并在中年成年人的生物学途径上与生物学途径有关，在中年成年人的生物学途径相关，种族和社会决定性差的角色和健康的社会决定因素以及加速的衰老现场的加速型脂肪级别与磷酸基因级的关系。 她的工作发现了中年脆弱的新颖且重要的性别特异性转录变化，增强了人们对脆弱进展的知识和潜在的治疗靶标知识，以防止脆弱并降低差异。 Pravitt Gourh，Niams Gourh博士是非裔美国人硬皮病患者的最大队列（n = 1300）。 目的是研究非裔美国人（AA）人群中的硬皮病（系统性硬化症，SSC），（i）鉴定增加SSC易感性的基因，以及（ii）了解这些基因引起SSC的基本机制。基因组广泛的关联研究和外显子组测序已导致鉴定HLA和非HLA基因，从而提高了AA种群的SSC易感性。他正在扩大该领域的工作，以包括健康的社会决定因素（SDOH），因为它们与遗传因素（包括遗传混合物）的相互作用可能有助于解释非裔美国人患者的硬皮病患病率和严重程度。 钱德拉·杰克逊（Chandra Jackson） 杰克逊研究小组（Jacksons Research Group）正在调查身体和社会环境如何影响心脏代谢健康中的种族和社会经济差异，对睡眠健康的影响特别感兴趣。她发表了表明，在非洲裔美国成年人中，增加（稳定）歧视（稳定）和睡眠质量下降之间存在纵向关联。在横截面分析中，较高的歧视与睡眠持续时间较短，与压力无关。在一项针对非洲裔美国人的阻塞性睡眠呼吸暂停（OSA）和夜间血压的研究中，她发现OSA和夜间低氧血症与高夜间血压有关，这可以帮助解释高血压的种族差异。她的博士后研究员（由NIMHD DIR资助）发表了一篇文章，讲述了与睡眠相关的心脏功能中亚临床种族 - 种族差异有关，该文章通过在生命过程中包括可修改的身体和社会环境来扩展科学方法，以确定针对原始预防的干预点。 蒂芙尼·鲍威尔·威利（Tiffany Powell Wiley），NHLBI 鲍威尔·威利（Powell-Wiley）实验室继续探索高风险高风险的非裔美国妇女中心血管危险因素和健康状况的种族差异。 她正在领导合作的努力，以在华盛顿特区的主要非裔美国人社区建立基于社区的心血管筛查诊所，以招募更多的非洲裔美国人参与临床研究以解决差异。 她出版了一个非常有用的框架，展示了健康的社会决定因素（SDOH）之间的联系（机制），该框架涵盖了影响健康的经济，社会，环境和社会心理因素，以及它们在心血管疾病（CVD）的发展中所起的重要作用，以及CVD的疾病率和死亡率和死亡率。 Anne E. Sumner，医学博士，NIDDK Sumners博士的工作重点是（a）改善糖尿病的检测和预防及其在非洲血统中的并发症； （b）确定糖尿病和心脏病的社会决定因素，以及（c）培训非洲医生以及代表性不足的少数群体成为临床研究者。萨姆纳（Sumner）博士和她的学员一直在努力分析黑人观察队列研究中萨姆斯糖尿病博士和心脏病的数据。截至2022年8月，她在该队列中招募了934名黑人，特别是229名非裔美国人和605名非洲移民成年人。此外，她发表了一项最近的研究，该研究评估了居住在开普敦的1,274名南非人，以检查将HBA1C与糖化白蛋白（GA）相结合的，可以改善患血糖症的检测。 他们在非洲人群中首次证明了体重指数（BMI）和HBA1C之间的正相关以及BMI和GA之间的负相关性。因此，结合这两个非散发标志的血糖标记可改善BMI类别中血糖症的检测。 凯尔·梅西尔（Kyle Messier），尼斯 Kyle Messiers博士实验室有两个总体主题：（1）地理空间暴露，差异和风险映射； （2）与毒理学的时空映射连接。 他发表了一项分析，该分析是系统地比较了多个尺度的城市变化，从超地（<100 m）到区域（> 10 km），并评估了不同种族和种族的居民所经历的室外空气污染的后果，通过创建一组独特的广泛且高分辨率的污染物（no no carbor）（ull carbor）（ullt and notable and notical and carthe and nike and carly，no and carbor and notecy and carthe and of。 通过在旧金山湾区四个县的全面覆盖范围监控，他们发现，对于西班牙裔和黑人人口，UFP，NO和NO2的中位数浓度比人口平均水平高出8至30％。 他们的结果说明了如何在人口规模上详细且广泛的细节污染观测来增加有关空气污染危险差异的新见解。