About the Investigator:

Prof. Avram Hershko, along with his colleagues, Profs. Aaron Ciechanover (also an ICRF Research Professorship grantee) and Irwin Rose, were awarded the Nobel Prize in Chemistry in 2004 for their earlier work discovering how the chemical, ubiquitin, works to control protein degradation as part of the process of mitosis (cell division). This work, in turn, was the basis for the development of a drug, Velcade®, the first effective therapy for multiple myeloma, a cancer of the blood.

About the Research:

Mitosis is the normal process that occurs when cells replicate themselves. This process separates chromosomes between the daughter cells and enables organs to grow when appropriate. During mitosis in normal cells, pairs of identical chromosomes, which are packets of genes, duplicate, and one set moves to each side of the cell before a new cell membrane is formed and one cell splits to become two.

Mitosis involves several phases which are regulated by proteins that ensure the process moves from phase to phase in a normal, precisely-orchestrated pattern. Cancer can result when this process does not proceed in the normal pattern. A complete understanding of this complex process and the numerous biochemical changes that regulate it is critical to understanding cancer, which always starts as abnormal cell division.

One of the abnormalities that can occur in mitosis is aneuploidy – when identical sets of chromosomes have not migrated into each of the daughter cells. This results in daughter cells with unequal numbers of chromosomes. Following a faulty division, some cells have too many chromosomes, while their partner now has too few. This inequality is key for the development of tumors: too many growth-stimulating genes in a cell can lead to uncontrolled growth, and too few inhibitors of growth in a cell can also lead to uncontrolled growth. Aneuploid cells are present in 70% of solid tumors, and play a key role in the development of cancer. The movement of the duplicated chromosomes into each daughter cell is called chromosome segregation and is a key aspect of mitosis. The Hershko lab is studying the roles of the proteins that control chromosome segregation, with the goal of identifying how we might therapeutically inhibit the development of aneuploid cells.