Chung-Jung Li, MSc, PhD

Early Career: My early career contributions were focused on Duxbl Expression and Influences in Myoblast Differentiation. Duxbl, whose homeodomain exhibits the highest identity (67 %) to human DUX4, a candidate gene of facioscapulohumeral muscular dystrophy (FSHD). Our team aimed to decipher the roles of Duxbl in myogenesis and postnatal regeneration, I mainly focused on the temporal expression of Duxbl and myogenic regulatory factors (MRFs). I further tried to dissect the underlying mechanism on ectopic expression of Duxbl during muscle differentiation. In the end, we found that overexpression of Duxbl accelerate myoblast proliferation but inhibit muscle differentiation via mediating MyoD downstream genes expression.

Master Career: My master research was to identify miRNA candidates required for regulating motor neuron subtypes. I took advantage of using embryonic stem cell (ESCs) differentiation approach, together with knockout mouse analyses to prove miRNA is important to regulate motor neuron subtype diversification. I further worked together with people in JAC Laboratory to analyze our microarray/RNA seq raw data and identified several miRNAs might participate in the regulation for motor neuron subtype diversification. I later performed luciferase assay to prove the direct interaction between miRNA and its targets.

Graduate Career: I continued my master project and tried finished it. With the collaboration with Prof. Qing Nie from the Mathematics Department of UC Irvine, we finally uncovered a novel microRNA (miRNA)/Hox gene expression network that contributes to the dynamic control of Hox gene expression and proper motor neuron(MN) subtype identities during development. This model was established with in silico mathematical simulations and further examined by embryonic stem cell differentiation systems and mouse and chicken embryos. Finally, we published “MicroRNA Filters Hox Temporal Transcription Noise to Confer Boundary Formation in the Spinal Cord” in Nature Communications. In the second parts of my graduate career, my research contribution is focused on how the differentiated cell decide their cell fate at the boundary during motor neuron development. With the collaboration with Prof. Tian Hong from National Institute from Department of Biochemistry and Cellular and Molecular Biology of UT Knoxville and Prof. Edwina McGlinn from Australian Regenerative Medicine Institute of Monash University, we revealed a previously underappreciated feedback mechanism that may have widespread functions in cell fate decisions and tissue patterning. I used the developing spinal cord as a paradigm and show that canonical, transcription-driven feedback cannot explain robust lineage segregation of motor neuron subtypes marked by two cardinal factors, Hoxa5 and Hoxc8. We propose a feedback mechanism involving elementary microRNA-mRNA reaction circuits that differ from known feedback loop-like structures. I mainly focus on the temporal expression of Hoxa5 and Hoxc8 along RC axis of spinal cord during development.Through mathematical analysis, we explain intuitively the hidden source of this feedback. I further used embryonic stem cell differentiation and mouse genetics to corroborate that microRNA–mRNA circuits govern tissue boundaries and hysteresis upon motor neuron differentiation with respect to transient morphogen signals.