Interdisciplinary Training

Zizhen Yao

“Molecular mechanisms for inactivation of MyoD-mediated muscle differentiation in rhabdomyosarcomas.”

Our major objective of this study is to apply computational analysis of high throughput microarray, mass spectrometry, and next generation sequencing (NGS) of transcription factor binding sites, as well as protein structure modeling techniques to study the molecular defects in the differentiation program of rhabdomycosarcomas (RMS). MyoD is a master transcription factor that serves as nodal points in the muscle differentiation process. In this study, we will test the following hypotheses on the cause of impaired MyoD-mediated differentiation program in RMS:  1. RMS lacks a MyoD cofactor necessary for differentiation; 2. deficiency of E-protein, a MyoD dimerization partner, prevents MyoD binding and/or activation; and 3. Msc, a known repressor of muscle differentiation, interferes with normal MyoD functioning. The significance of this project is twofold. From biological perspective, RMS serves as a nice model to study the molecular regulation of the transition from a growth phase to a differentiation phase in normal development and cancer, so identification of the molecular steps in this transition will provide new strategies for developing cancer therapeutics based on cell differentiation. From computational perspective, based on the experience we gather from this project, we can optimize our analytical strategies, generalize the computational pipeline to make it easily applicable to similar problems, and develop tools that will be available to public via BioConductor.