Academic Background
Jennifer Benanti received her B.S. from the University of California, San Diego in 1996, and her Ph.D. from the University of Washington and the Fred Hutchinson Cancer Research Center in 2003. She did her postdoctoral work at the University of California, San Francisco from 2004-2010, where she was supported by a Damon Runyon Cancer Research Foundation Fellowship and a Pathway to Independence Award from the NIH. Dr. Benanti joined the Program in Gene Function and Expression at the University of Massachusetts Medical School in spring 2010. She is a recipeint of the 2011 Smith Family Award for Excellence in Biomedical Research.
Regulation of Cell Growth and Division
The Benanti laboratory is interested in the molecular mechanisms that control cell growth and proliferation, and in understanding how these mechanisms are disrupted in cancer cells. The lab is studying how transcription, phosphorylation and protein degradation contribute to the regulatory network that controls the cell cycle. To do this, they use genetics, biochemistry, and cell biology, in both yeast and human cells, with the goal of understanding properties of cell cycle control networks that are conserved in diverse systems.
Transcriptional control of the cell cycle
Cell proliferation is controlled by a tightly-regulated transcriptional program, which ensures that cells only proceed through the cell division cycle when they receive the appropriate signals. This program is established by a network of conserved transcription factors, many of which are mutated or misregulated in cancer cells. The Benanti lab uses yeast as a model system to study the connections between cell cycle-regulatory transcription factors, and to determine how phosphorylation and ubiquitination coordinate their activities. These studies are complemented by work in human cells aimed at understanding the regulation of oncogenic transcription factors that are core components of the cell-cycle network.
Figure 1. The cell cycle-regulatory transcription factor network in yeast.
Cell cycle-regulation of chromosome strucure
Chromosome conformation is cell cycle-regulated so that chromosomes are tightly compacted during mitosis to facilitate their segregation, and decondensed during interphase to facilitate DNA-dependent processes such as replication and transcription. Understanding how chromosomes transition between these different states is important in order to understand how cells maintain a stable genome. The Benanti lab is investigating how cell cycle-regulation of chromatin proteins functions to coordinate chromosome strucutre with the cell cycle, and aims to understand the consequences of disrupting this regulation.
Figure 2. Interphase and mitotic chromosome strucutre.
Control of the cell cycle by the ubiquitin-proteasome system
Protein degradation via the ubiquitin-proteasome system is essential for cells to grow and divide. Consistent with this role, numerous ubiquitin ligases (E3s) that promote protein degradation, as well as deubiquitinating enzymes (DUBs) that antagonize E3 function, are mutated in cancer cells. However, the targets of most of these enzymes remain unknown. The Benanti Lab is using yeast as a model system to determine how conserved E3s and DUBs recognize and select their substrates, and to develop proteome-wide approaches to identify targets of these critical enzymes.