Welcome to the Rual Lab!
The research interests of the Rual lab lie in the field of cancer systems biology and the use of proteomic approaches to study cellular networks. We focus on the systematic analysis of protein interactions in biological systems and their relationship to human disease, with particular interest in the Notch pathway and the MLL/HOXA9 axis.
CHARACTERIZATION OF THE NOTCH MOLECULAR NETWORK IN GLIOBLASTOMA AND MEDULLOBLASTOMA.
How does the ensemble of Notch-related interactions govern biological processes in the cell and how can disruptions of these interactions lead to pathophysiological events such as the ones observed in brain tumors? Notch defines a fundamental cell signaling mechanism controlling metazoan development and it has emerged recently as an important contributor to glioblastoma and medulloblastoma, ones of the most common and aggressive forms of brain tumors. Given the extraordinary complexity and context-dependence of Notch signal modulation, a systematic characterization of Notch-related proteins and associated protein-protein interactions in brain cells as well as the integration of all the functional relationships between these proteins into a comprehensive framework should shed light on the complex molecular mechanisms that govern this pathway and provide insights into the circuitry that is relevant to Notch-related pathologies. We propose to generate a comprehensive map of the Notch molecular network by taking advantage of a unique protein-protein interaction mapping platform that combines the use of two complementary technologies for high-throughput protein interaction mapping, i.e., the yeast two-hybrid system (Y2H) and co-affinity purification coupled to mass spectrometry analysis (coAP-MS). This “interactome” approach will define novel proteins and protein-protein interactions involved in modulating the activity of Notch signal in brain cells and, upon biological validation of these candidates in cell-based and in vivo models of brain tumors, should offer the means to manipulating the Notch molecular network for therapeutic benefit.
CHARACTERIZATION OF THE MLL AND HOXA9-REGULATED ENHANCEOSOME MOLECULAR NETWORKS IN ACUTE LEUKEMIA
In collaboration with the Hess Lab and other UMMS Labs, the Rual Lab is using a similar "interactome" approach to define the molecular networks in which MLL/HOXA9 axis related proteins are involved in the context of hematopoiesis and leukemia. Our research on the MLL/HOXA9 axis is sponsored by the WES Foundation (http://www.wheneveryonesurvives.org/wesearch2012.html).