BLR&D Research Career Development Transition Award Application

BLR

• 批准号: 10012726
• 负责人: Aliza Pham Wingo
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 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 2025-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10012726
• 关键词: Address; Affect; Alzheimer' s Disease; Anxiety; Area; Autopsy; Award; Awareness; Behavioral; Biological Models; Biological Psychiatry; Blood; Brain; Caring; Chromosome 1; Cognitive; Communication; Complex; DICER1 gene; Data; Data Set; Dementia; Development; Doctor of Medicine; Elderly; Etiology; Event; Female; Formulation; Funding; Future; Genes; Genetic; Genetic study; Genomic medicine; Genotype; Goals; Health; Healthcare; Human; Impaired cognition; Individual; Intervention; Journals; K-Series Research Career Programs; Life; Life Experience; Mass Spectrum Analysis; Medical center; Mental Depression; Messenger RNA; Meta-Analysis; MicroRNAs; Molecular; Multiomic Data; National Institute of Mental Health; Nature; Neurobiology; Outcome; Paper; Participant; Pathway interactions; Patient Care; Post-Traumatic Stress Disorders; Prefrontal Cortex; Pregnant Women; Principal Investigator; Proteins; Proteome; Proteomics; Psyche structure; Psychiatrist; Psychiatry; Publications; Publishing; Regulation; Research; Research Personnel; Research Priority; Role; Seminal; Shapes; Stress; Symptoms; Systems Biology; Transition Career Development Award (K22); Translating; Trauma; United States National Institutes of Health; Veterans; Weight; Woman; Work; base; brain tissue; career; comorbid depression; coping; dementia risk; effective intervention; epidemiology study; experience; genetic variant; genome wide association study; geriatric depression; high risk; innovation; intergenerational; mRNA Expression; multiple omics; novel; novel therapeutics; offspring; positive emotional state; programs; protective effect; protein expression; psychologic; resilience; statistics; transcriptome; transcriptomics

The applicant, Aliza Wingo, M.D., M.Sc., is a board-certified psychiatrist and principal investigator at the Atlanta VA Medical Center. The first focus of Dr. Wingo’s research is to identify the genetic and molecular contributors to psychological resilience, PTSD, and depression, respectively. She is keenly aware of the complex relationships among these three facets of mental condition and also works to identify common and distinct mechanisms among them. The second focus of Dr. Wingo’s work is to identify how resilience, PTSD, and depression share common genetic and molecular basis with Alzheimer’s disease dementia. Through studying psychological constructs, she aims to identify novel pathways for enhancing resilience, treating PTSD/depression, and identifying novel causes of Alzheimer’s dementia that could be leveraged for new therapies. This work is currently supported by a Merit Review award from the VA, an R01 from the NIA/NIH, and a U01 from the NIMH/NIH. With regard to resilience, Dr. Wingo has shown that a genetic variant on chromosome 1 (rs322931) and brain expression level of miR-181 contribute to resilience (Wingo et al, Molecular Psychiatry, 2016). Resilience here is conceptualized as having high levels of positive emotions and/or sense of life purpose and meaning after adverse or traumatic life experiences. In her current funded Merit Review, Dr. Wingo examines brain microRNA profile to identify a microRNA signature of resilience. Next, she will use systems biology approach to identify brain transcriptomic drivers of resilience using brain transcriptome. Finally, she will examine the mRNAs and proteins that are downstream targets of the resilience-associated microRNAs with the overall goal of identifying novel genes regulating resilience. Regarding PTSD and depression, Dr. Wingo has shown that DICER1 and microRNA regulation pathway contributes to PTSD and depression (Wingo et al, Nature Communications, 2016). In this CDTA, Dr. Wingo proposes to harness deep human brain proteomes quantified by mass spectrometry from post-mortem brain tissues as a reference to impute brain protein expression level in Veterans who have genotyping. The imputed protein expression profile is then used for a proteome-wide association study of PTSD and depression, respectively, to identify proteins in the brain that predispose to PTSD or depression. In addition, epidemiological studies have observed that offspring of pregnant women suffering from PTSD or depression have higher risk for developing psychological or behavioral issues later in life. To investigate the mechanisms behind this intergenerational association, Dr. Wingo has been funded by a U01 to examine offspring’s blood- based transcriptome and global microRNA profile. These findings are highly relevant to female Veterans who suffer higher risk for PTSD and depression. Regarding dementia, Dr. Wingo has shown that hundreds of proteins in human brain are altered with cognitive decline in advanced age (Wingo et al, Nature Communications, 2019). Since large epidemiological studies have observed that depression, especially late-life depression, increases the risk for dementia, Dr. Wingo is funded by an R01 to elucidate molecular mechanisms underlying detrimental effects of depression and protective effects of life purpose on Alzheimer’s dementia risk using multi-omics data from post-mortem brain tissues. Through studying the genetic and molecular mechanisms underlying the conditions that disproportionally affect our Veterans – PTSD, depression, and Alzheimer’s dementia, Dr. Wingo hopes to contribute to advancing our understanding of their etiologies to develop novel and effective interventions. As a long-term goal, Dr. Wingo aspires to carry out novel and innovative research questions to make transformative impact on the health and resilience of our Veterans.

申请人Aliza Wingo，医学博士，理学硕士，是一名委员会认证的精神病学家，也是美国国立卫生研究院的首席研究员