Research in the Amendt laboratory focuses on three major areas, 1) studying the expression and regulation of transcription factor genes and signaling processes involved in craniofacial/tooth development 2) the molecular basis of selected human genetic disorders and 3) the role of stem cells and microRNAs in regulating craniofacial and regenerative medicine. My laboratory is dedicated to understanding the role of transcription factors and signaling pathways in tooth and craniofacial development. The overall goal of the laboratory is to elucidate the combinatorial code of factors and mechanisms required for normal development of teeth and craniofacial structures. These data can then be used to understand the molecular control of these developmental processes.

The planar cell polarity effector gene, Fuz, and FoxJ1 transcription factor coordinate cell polarity, ciliogenesis, Hedgehog (Hh) and Wnt signaling and gene expression during dental and craniofacial development. Fuz signaling mechanisms are both cilia dependent and cilia independent and both mechanisms regulate different signaling pathways. The Fuz null mice have massive craniofacial defects including cleft palate and tooth agenesis. FoxJ1 null mice have late stage tooth developmental anomalies affecting enamel formation. Our studies have uncovered a link between these two factors regulating both cilia and craniofacial/tooth development. We are working to understand the role of Fuz and FoxJ1 in human birth defects. Our newly identified human FUZ mutations are critical to understanding the molecular basis of FUZ in developmental anomalies.

We are currently using microRNAs (miRs) to control stem cell development and to regenerate tissues. We have begun to demonstrate a hierarchy of dental epithelial expressed transcription factors in regulating gene expression networks required for tooth morphogenesis. Dental miRs control stemness properties of the dental progenitors 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 progenitor cells.

We work on the hierarchical interactions of homeodomain, T-box, forkhead domain and Lim domain transcription factors in craniofacial/tooth development. These transcription factors interact separately or in concert together or with other factors to regulate gene expression in a temporal and spatial mechanism. The function and interaction of these factors plays a major role in the timing and development of teeth and craniofacial tissues.

I am committed and dedicated to training the next generation of scientists through mentoring both graduate students and post-doctoral fellows. My students are competitive and recruited for outstanding post-doctoral positions and post-docs have been successful in obtaining research positions. The T90 support mechanism is critical for the training of qualified students and post-docs.

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.

Research in the Amendt laboratory is funded by grants from the NIH.