Mechanisms underlying the multifaceted basis of craniofacial dysmorphogenesis

颅面畸形是人类最常见的先天缺陷之一， 其严重程度和程度各不相同。了解、诊断和治疗这些畸形需要 详细了解正常的遗传层次结构、细胞信号和细胞相互作用 颅面复合体内多种细胞类型的形态发生和整合。遗传和/或 破坏这些正常过程的环境扰动会导致颅面畸形。 鉴于人类头面部出生缺陷往往是零星的和非综合征的，很可能是 多因素扰动是这些缺陷的最常见原因。然而，我们在这方面有很大的差距 了解颅面发育的正常过程。此外，我们几乎没有 理解多因素相互作用如何扰乱正常发育。 这项R35提案将支持约翰·埃伯哈特博士实验室的独特研究计划。信令 在第一个程序中，研究了调节头面部形态发生的相互作用。第二个方案 研究头面部组织是如何彼此无缝结合的。第三个程序检查 环境和基因-环境的相互作用可能会扰乱颅面发育。 埃伯哈特博士是一位训练有素、多产的发育生物学家。他得到了支持 从他还是一名本科生时起，他就通过各种基于NIH的机制。他已经写了40本书 自他在德克萨斯大学奥斯汀分校建立独立实验室以来，共发表了28篇论文。他已经确立了自己的地位。 在颅面发育领域处于领先地位，并在肌肉-肌腱连接方面发表了开创性的出版物， 斑马鱼的腭部发育和基因-环境交互作用。埃伯哈特博士通常会被邀请出席 他的实验室在国内和国际会议上的工作。他还经常被要求提供科学的 服务，如赠款审查和组织/参加科学研讨会。埃伯哈特博士是一个不知疲倦的 门托。他不仅确保他的实习生的研究是一流的，而且还深入参与了他们的 科学事业。到目前为止，埃伯哈特博士的每一位有资格获得奖学金的实习生都 至少收到了一封。埃伯哈特博士还致力于增加STEM领域的多样性，并积极招募 来自不同背景的有前途的年轻科学家进入该领域。

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.