Early Warning Systems for Childhood and Adult Disorders

儿童和成人疾病早期预警系统

基本信息

批准号：
10624212
负责人：
Manish Arora
金额：
$ 95.68万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2028-03-31
项目状态：
未结题

项目摘要

Project Summary According to the developmental origins of health and disease hypothesis, many disorders originate via environmental exposures in fetal and early postnatal life. Such early life environmental exposures can alter the developmental trajectory by disrupting the homeostasis of one or more systems, and in doing so produce identifiable biochemical signatures characteristic of the disease process or outcome. However, the lack of a conceptual framework as well as technological barriers have hampered research in this area; consequently, many disorders are not detected until overt clinical signs appear in adulthood, at which point it is no longer possible to meaningfully alter the course of development or disease. We are proposing a new paradigm that will overcome these barriers to detect disease years before current clinical and biochemical tests. By doing so we will be able to predict, and even prevent and treat diseases decades before any clinical signs. Central to our proposal is an underappreciated characteristic of many human physiologic processes—they commonly exhibit highly temporally resolved biochemical rhythms (or cycles) when at homeostasis. The idea of biochemical rhythms in itself is not revolutionary; sleep cycles, body temperature, cortisol rhythms, and menstrual cycles are all examples of the rhythmic nature of human physiology operating at various intervals. Medical testing, however, seldom considers rhythmicity. We propose to develop not just a novel technology that analyzes dynamic rhythmicity of key biochemical pathways during fetal development and childhood to accurately detect marked and sustained deviations from homeostasis that would be prognostic of later-life disease onset, but also a new framework for understanding development not solely as a linear trajectory but as interconnected rhythmic processes embedded within the growth trajectory.

项目概要根据健康和疾病的发育起源假说，许多疾病起源于胎儿和出生后早期的环境暴露可能会改变生命早期的环境暴露。通过破坏一个或多个系统的稳态来改变发育轨迹，并在此过程中产生然而，缺乏疾病过程或结果特征的可识别生化特征。因此，概念框架和技术障碍阻碍了这一领域的研究；许多疾病直到成年后出现明显的临床症状才被发现，此时就不再需要注意了。有可能有意义地改变发育或疾病的过程。通过这样做，将克服这些障碍，在当前的临床和生化测试之前数年发现疾病。我们将能够在出现任何临床症状之前几十年预测、甚至预防和治疗疾病。我们的建议是许多人类生理过程的一个未被充分认识的特征——它们通常处于稳态时表现出高度时间分辨率的生化节律（或周期）。生化节律本身并不是革命性的；睡眠周期、体温、皮质醇节律和月经周期都是人类生理机能在不同时间间隔运行的节律性质的例子。然而，医学测试很少考虑节律性，我们建议开发的不仅仅是一种新技术。胎儿发育和儿童时期关键生化途径的动态节律性准确地检测体内平衡的显着和持续的偏差，这将是晚年生活的预后疾病的发作，也是一个新的框架，用于理解发展不仅是线性轨迹，而且是嵌入生长轨迹中的相互关联的节奏过程。