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Jean-Francois Rual

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Primary Appointment: Pathology Department
Primary PIBS Dept.: Molecular and Cellular Pathology
PubMed Name: Rual J
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 DESCRIPTION OF RESEARCH
  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 MLL/HOXA9 axis and the Notch pathway.


CHARACTERIZATION OF THE MLL AND HOXA9-REGULATED ENHANCEOSOME MOLECULAR NETWORKS IN ACUTE LEUKEMIA
As part of a complex ensemble of hematopoietic regulators, MLL and HOXA9 help maintain the balance between hematopoietic stem/progenitor cell (HSPC) self-renewal and myeloid/lymphoid cell differentiation in the bone marrow. Several genetic mutations observed in acute myeloid leukemia (AML) patients, e.g., MLL rearrangements, are associated with aberrant upregulation of HOXA9, thus disrupting the hematopoietic balance towards leukemogenesis. Systematic characterization of the molecular interactions in which HOXA9 and MLL/HOXA9-axis proteins are involved should shed light on the mechanisms that govern these proteins during both normal hematopoiesis and leukemogenesis. In collaboration with the Hess Lab, we are generating a comprehensive map of the MLL/HOXA9 molecular networks by taking advantage of a protein-protein interaction mapping platform combining the use of two complementary, high-throughput technologies, i.e., affinity purification coupled to mass spectrometry analysis (AP-MS) and the yeast two-hybrid system (Y2H). Our project on the MLL/HOXA9 axis is sponsored by the WES Foundation and the American Society of Hematology.



CHARACTERIZATION OF THE NOTCH MOLECULAR NETWORK IN BRAIN TUMORS
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 glioblastoma? Notch defines a fundamental cell signaling mechanism controlling metazoan development. It has emerged as a contributing factor in glioblastoma and medulloblastoma, ones of the most common and aggressive forms of brain tumors. Given the complexity and context-dependence of Notch signal modulation, a systematic molecular characterization of Notch-related proteins in brain cells should shed light on the complex molecular mechanisms that govern this pathway during brain tumorigenesis. The Rual lab is generating a comprehensive map of the Notch molecular network in brain cells. This “interactome” approach has defined novel candidate proteins and protein-protein interactions involved in modulating the activity of Notch signals. Upon biological validation of these candidates in cell-based and in vivo models of brain tumorigenesis, our project should offer the means to manipulating the Notch molecular network for therapeutic benefit.