What is the Cell Cycle?

In order for a living organism to grow their individual cells must increase in size, make exact replicas of all their genetic material, and then go through a process of division. This results in two daughter cells each with one complete copy of the genome.  Thus, in eukaryotic cells the mitotic cell cycle is characterized by four distinct phases.

Multicellular organisms, such as humans, contain a vast number of cells of many different types and functions. Some of these cells, e.g. blood producing cells from the bone marrow, are continuously produced by a population of continuously proliferating cells.  In contrast, neurosensory cells, such as the auditory sensory epithelium in the cochlea, go through a proliferative phase during development but then irreversibly exit the cell cycle and undergo dramatic morpholical changes. This means that these cells do not regenerate, even in the case of tissue injury.

Our laboratory seeks to better understand how cell cycle control molecules, the cyclins and their CDK partners, are differentially regulated to meet the specialized growth requirements of primary mammalian cells.  For example, we would like to know whether the redundancy of cell cycle control molecules in vertebrates has facilitated specialization of cellular growth control.  In addition, we seek to determine whether cell cycle gene activation in one cell type regulates the growth of others through a intracellular signals.  By understanding the pathways of multicellular growth control we hope to better understand how the process go awry in cancer cells and how we might be able harness the activity of cell cycle control molecules to induce regrowth in of post-mitotic tissues. 

Dysregulation of cell cycle control mechanisms is a universal characterstic of cancer cells, but may occur by multiple mechanisms. Additionally cancer involves changes which are synergistic with cell cycle gene mutations.  Our lab has shown that overexpression of the miR-106a~363^Xpcl1 miRNA cluster is causes lymphoma, and that this is synergized by concurrent loss of the p27^Kip1 Cdk inhibitor protein. Likewise Kip1 and Xpcl1 control the growth and differentiation of normal T-lymphocytes through a combination of cell autonomous and non-autonomous mechanisms.