Assistant Professor - Research
PhD: Louisiana State University, 2010
Phone: (225) 578‐8632
Lab Phone: (225) 578-7392
Every living cell has the major activity of coordinating cell growth with the cell cycle. Protein synthesis, an integral part of this process is intimately dependent on ribosomes and their biogenesis. In fact ~80% of the cells energy expenditure is related to ribosome biogenesis. I am interested in the process by which the cell senses the production of ribosomes, and understanding the cues that elicit stress responses upon stalled or aberrant biogenesis. Dysregulation or mutations in genes required for ribosome biogenesis can lead to several diseases collectively referred to as ribosomopathies. These conditions include, but are not limited to Treacher-Collins Syndrome, Diamond-Blackfan Anemia (DBA) and Shwachman-Diamond syndrome. Understanding the signaling pathways involved in the progression of these conditions may yield new drug targets that will help alleviate the associated symptoms. Hence, the major question my research is designed to answer is, “When ribosome biogenesis is perturbed, what does the cell sense that leads to cessation of the cell cycle and subsequent apoptosis?”
I use the budding yeast S. cerevisiae as a model system, and like depletion of ribosomal proteins in metazoans, in the budding yeast S. cerevisiae, depletion of ribosomal proteins often leads to a cell cycle arrest. In both yeast and mammalian models, cell cycle defects associated with aberrant biogenesis often precede bulk protein synthesis defects indicating a voluntary stress response as opposed to inability to translate new proteins. However, unlike metazoans where this stress response appears to be governed by p53-MDM2 interactions, yeast does not have a characterized p53 or MDM2. This observation can be interpreted in a couple of ways. First, nucleolar stress responses in yeast could be a mediated through unique pathway that is not conserved in metazoans or secondly, the yeast might have a conserved ancestral pathway that has been further enhanced in metazoans to address their complex cellular and organismal needs and that this enhanced pathway has become epistatic to the common ancestral pathway.
The overall goal of my research is to understand the complex mechanism for nucleolar stress responses.