Dr. Jia L. Song
University of Delaware
Department of Biological Sciences
Wolf Hall

Research Interests

The potential for forming a new organism begins at fertilization, when the sperm meets the egg. Across species from the worm to the human, development of the newly fertilized egg to a juvenile or an adult requires the careful regulation of cell growth, differentiation, and morphogenesis. Different Dr. Jia Songcell types make different sets of proteins, even when their genomes are identical. What makes each cell type unique is a direct result of differential gene expressions mediated by transcription factors and signaling molecules in response to chemicals and proteins in the cell and the environment. Dysregulation of important genes involved in developmental decisions can lead to human diseases. Our research addresses one of the key questions in developmental biology: How are genes regulated during early development?

In 2006, Dr. Andrew Fire and Craig Mello were awarded the Nobel Prize in Physiology or Medicine for their work which discovered double stranded RNAs that trigger the suppression of gene activity. Their discovery revealed a novel mechanism of gene regulation mediated by microRNAs (miRNAs), which are small RNA molecules of 22 bases long that are expressed by all animals and plants. miRNAs are critical for all aspects of life, including the development of an organism and the physiological functions of cells and tissues. Because miRNAs are involved in regulating so many biological processes, their malfunction leads to many diseases such as cancer. With the increasing application of miRNAs in the treatment and diagnosis of various diseases, miRNAs have become an important tool in biological and medical research. With thousands of miRNAs identified, a pressing challenge is now to understand their specific biological functions by identifying their gene targets.
Our laboratory focuses on understanding the regulatory role of miRNAs in early development. We use the invertebrate sea urchin as a model organism. Since sea urchins belong to a sister group to chordates that includes us humans, their developmental processes have much in common with vertebrates. The sea urchin animal model has had a long history of contributing to our knowledge in the field of developmental biology, including fertilization and early developmental events. An important advantage of using the sea urchin to examine the regulatory role of miRNAs is that unlike vertebrates that have hundreds of miRNAs that have multiple members within a miRNA family with redundant functions, majority of the sea urchin miRNAs lack multiple members within a family, making it an attractive model to examine the function of individual miRNAs. The sea urchin model is also amenable to high-throughput, systematic analysis; therefore, we can rapidly assess the biological functions of specific miRNAs.

Current Projects:
• miRNA-124 is the most abundant miRNA in the adult brain of mice and is found in mature neurons in humans. The function of miR-124 appears to be the repression of non-neuronal transcripts Sea urchin miR-124 has the exact same sequence as the human miR-124. We hypothesize that miR-124 is essential for the development of the neural development and patterning. We will analyze the loss-of-function and gain-of-function phenotypes of miR-124 by identifying cell fate and pattern changes with cell type specific molecular markers. Bioinformatic analysis of candidate genes also will be used to identify genes potentially regulated by miR-124. This aim will identify the specific cell types and genes that are regulated by miR-124.

• Another highly conserved miRNA that we focus on is miR-31 that has been examined mostly in the context of human cancer and more recently in bone formation. We use shotgun proteomics approach in identifying novel miR-31 functions as well as in discovering the regulatory mechanism of miR-31. Our results indicate that miR-31 regulates key transcription factors in the skeletogenesis gene regulatory network in the sea urchin and vertebrates.

• Highly conserved Wnt signaling pathways are critical for proper development. We hypothesize that the components of the Wnt signaling pathways are regulated by miRNAs. Using luciferase constructs and site-directed mutagenesis, we identified miRNA regulation on Disheveled and β-catenin, which encode key proteins central to Wnt signaling activation.   Since miRNAs and components of the Wnt signaling pathways are known to be dysregulated in human diseases, results from our study may aid in therapeutics development resulting from aberrant miRNAs and Wnt signaling pathways.


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