Andrew Koff: Overview
In the past, this labs study of G1 cyclins and the Kip family of cdk inhibitors contributed greatly to our understanding of the consequences, both cellular and organismal, of dysregulating the decision of mammalian cells to enter and exit the cell cycle during development and during the formation and progression of cancer cells. Thus, it is well positioned to now turn its attention to understanding how quiescent non-cycling cells maintain themselves in a state in which it might be years before they re-enter the mitotic cell cycle.
Work in our group over the last four years studying the effect of CDK4/6 inhibition in cancer cells has uncovered a new relationship between quiescence and senescence, a more permanent form of cell cycle exit from which cells cannot re-enter the cell cycle irreversible. We suspect that similar to the molecular machine that governs the decision to enter/exit the cell cycle, a small set of genetic elements conspire to control the reversible/irreversible decision operating to control the progression of quiescent cells into senescence, a transition that we call senescence after growth arrest or SAGA.