Mechanisms underlying the multifaceted basis of craniofacial dysmorphogenesis

颅面畸形发生的多方面基础机制

基本信息

批准号：
10645146
负责人：
JOHANN K EBERHART
金额：
$ 98.06万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2027-06-30
项目状态：
未结题

项目摘要

Craniofacial dysmorphologies are some of the most common human birth defects and can be extremely variable in their severity and extent. Understanding, diagnosing and treating these dysmorphologies requires a detailed understanding of the normal genetic hierarchies, cell signaling and cellular interactions that drive the morphogenesis and integration of the multiple cell types within the craniofacial complex. Genetic and/or environmental perturbations that disrupt these normal processes can cause craniofacial dysmorphologies. Given that human craniofacial birth defects tend to be sporadic and non-syndromic, it is most likely that multifactorial perturbations are the most common cause of these defects. However, there are major gaps in our understanding of the normal processes in craniofacial development. Furthermore, we have very little understanding of how multifactorial interactions disrupt normal development. This R35 proposal will support the unique research program of Dr. Johann Eberhart’s lab. The signaling interactions mediating craniofacial morphogenesis are examined in the first program. The second program examines how craniofacial tissues integrate seamlessly with one another. The third program examines the environmental and gene-environment interactions that can disrupt craniofacial development. Dr. Eberhart is an extremely well trained and productive developmental biologist. He has been supported through various NIH-based mechanisms ever since he was an undergraduate student. He has authored 40 total publications, 28 since establishing his independent lab at UT Austin. He has established himself as a leader in the field of craniofacial development and has pioneering publications on muscle-tendon attachments, zebrafish palatal development and gene-environment interactions. Dr. Eberhart is routinely invited to present the work from his lab at national and international meetings. He is also regularly asked to provide scientific service, such as grant reviews and organizing/participating in scientific workshops. Dr. Eberhart is a tireless mentor. He not only ensures that his trainees research is top notch, but is also deeply engaged with their scientific careers. To date, every one of Dr. Eberhart’s trainees that have been eligible for fellowships have received at least one. Dr. Eberhart is also committed to increasing diversity in STEM fields and actively recruits promising young scientists from diverse backgrounds into the field.

颅面畸形是一些最常见的人类出生缺陷，并且可能极其严重理解、诊断和治疗这些畸形的严重程度和程度各不相同。详细了解驱动细胞生长的正常遗传层次、细胞信号传导和细胞相互作用颅面复合体中多种细胞类型的形态发生和整合。破坏这些正常过程的环境扰动可能会导致颅面畸形。鉴于人类颅面出生缺陷往往是散发性和非综合征性的，最有可能的是多因素扰动是这些缺陷的最常见原因，但是，我们的研究还存在重大差距。此外，我们对颅面发育的正常过程了解甚少。了解多因素相互作用如何扰乱正常发育。该 R35 提案将支持 Johann Eberhart 博士实验室的独特研究项目“信号传导”。在第一个程序中检查了介导颅面形态发生的相互作用。第三个程序检查颅面组织如何彼此无缝整合。环境和基因-环境相互作用可能会破坏颅面发育。艾伯哈特博士是一位训练有素且富有成效的发育生物学家，他得到了支持。自本科生起，他就通过各种基于 NIH 的机制，撰写了 40 篇论文。自从在 UT Austin 建立独立实验室以来，他已发表论文总数 28 篇。颅面发育领域的领导者，并发表了有关肌肉肌腱附件的开创性出版物， Eberhart 博士经常受邀发表演讲。他还经常被要求在国家和国际会议上提供他实验室的工作成果。埃伯哈特博士孜孜不倦地提供服务，例如资助审查和组织/参加科学研讨会。他不仅确保学员的研究是一流的，而且还深入参与他们的工作。迄今为止，艾伯哈特博士的每一位有资格获得奖学金的学员都已经取得了科学生涯。 Eberhart 博士还致力于增加 STEM 领域的多样性并积极招募人员。来自不同背景的有前途的年轻科学家进入该领域。