Size Control of the Nucleus and other Organelles

 

    The nucleus is the compartment within each cell that contains the genetic information directing how the cell grows and behaves. Large cells generally have large nuclei, while smaller cells have smaller nuclei. Little is known about how cells regulate their nuclear size. This is an important question because nuclei in cancer cells are usually inappropriately enlarged, a change that pathologists use to diagnose and stage disease. We presently know very little about what causes large nuclear size or what the consequences are for the cancer patient.

To understand the importance of nuclear size changes in cancer, we first must understand how nuclear size is controlled. Factors were identified that determine nuclear size in two different size frog species. Similar systems regulate cell growth in humans and frogs, and frog research has informed a variety of human diseases, including cancer. Discoveries about nuclear size control in frogs will thus also hold true in humans, producing useful and important information for the cancer community.

Part of the work in the Levy lab is focused on translating our findings about nuclear size control in frogs to humans. Specifically, we want to determine how nuclear size affects cancer cell growth by directly altering nuclear size in human cells grown in a dish. We will test if causing nuclei to become bigger confers cancerous growth on those cells, and conversely, if shrinking cancer cell nuclei reduces severity of the disease by slowing cell growth and metastatic potential.

Another focus of our lab is to analyze early frog development when fertilized frog eggs undergo developmental cell divisions that result in reduced cell and nuclear size. We will determine what factors regulate these changes in nuclear size and how altering nuclear size in frog embryos affects their development. In many ways the uncontrolled growth of cancer is similar to the growth of developing embryos. In fact, cancer may arise from reactivation of embryonic growth programs in otherwise normal cells. Understanding nuclear size regulation in embryos will therefore inform cancer.

The overall goal of this research is to elucidate how nuclear size is regulated during embryogenesis as well as the function of proper nuclear size control in cell growth and development. This new information will help us to understand how nuclear size becomes deregulated, contributing to cancer formation and progression. Understanding the molecules and mechanisms that regulate nuclear size in cancer cells will offer novel approaches to cancer diagnosis and treatment that target nuclear size, as well as identify new cancer susceptibility factors associated with altered nuclear size that could aid in prevention. The proposed basic biomedical research on nuclear size regulation will provide the foundation for cancer diagnosis, treatment, and prevention.