Brad A. Amendt


Research in the Amendt laboratory focuses on three major areas, 1) studying the expression and regulation of genes and co-factors involved in mammalian development 2) the molecular basis of selected human genetic disorders and 3) the role of stem cells and microRNAs (miRs) in regulating craniofacial development and regenerative medicine. The overall goal of the laboratory is to elucidate the combinatorial code of transcription factors and mechanisms required for normal development of craniofacial structures and teeth. These data can then be used to understand the molecular control of these developmental processes. 
Our research has expanded to include Homeobox and T-Box factors, Fox, Irx1, HMG and Sox genes. We are exploring the role these factors play in regulating gene expression networks required for morphogenesis. 
Our research has identified HMGN2 as a master regulator of embryonic gene expression. HMGN2 is associated with euchromatin and recruits transcription factors to active chromatin. We have shown that HMGN2 forms a transcriptionally inactive complex with multiple transcription factors that become activated through Wnt/β-catenin signaling. 
Sox2, Irx1, Pitx2, Tbx1 and FoxO6 all regulate craniofacial/tooth stem cell proliferation and differentiation to control face morphology. These factors work in concert to fine tune gene expression networks (GRNs) required for normal craniofacial development including palatogenesis. We are using our knowledge of their molecular function to stimulate tissue regeneration in cleft palate and craniosynostosis. Organ cultures combined with mouse models for these defects reveal specific methodologies for treatments of these genetic defects.
We are currently using miRs to control stem cell development and to regenerate tissues. miRs control stemness properties of craniofacial tissue progenitor cells and we have identified several novel miR transcription factor targets. These targets also function in many other developmental processes. We are using miRs to program embryonic stem cells and reprogrammed dental/craniofacial progenitor cells. The function and interaction of miR with transcription factors plays a major role in the timing and development of teeth and craniofacial tissues. 
We have developed the Plasmid-Based microRNA Inhibitor System (PMIS) to determine the roles of miRs during craniofacial development. The PMIS effectively knocks down the activity of miR clusters to allow for the analyses of multiple miRs on separate chromosomes. This is the first demonstration of an in vitro system to knock down miR clusters and we will make mice expressing miR inhibitors. These mice will be provided to researchers as a new tool to study miR function.
Human genetic defects provide a wealth of knowledge to our understanding of gene function and in reciprocation understanding gene function allows us to better understand genetic defects. The laboratory strives to provide the basic framework for the development of technologies towards treating human genetic defects. Preparing and training graduate students for a career in research is an extremely important aspect of my career and required to advance knowledge.
The Amendt Laboratory is supported by grants from the NIH/NIDCR.

Brad A. Amendt
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1 - 675 B BSB