Dr. Bargonetti's research focuses on the relationship between the hormone estrogen and a genetic pathway that is supposed to get rid of cells that are growing out of control.

Dr. Bargonetti received her B.A. from the State University of New York College at Purchase and her M.S. and Ph.D. from New York University. After a postdoctoral fellowship at Columbia University, she joined the faculty at Hunter College. She is the recipient of numerous awards, including a Breast Cancer Research Foundation Award.

Dr. Bargonetti studies p53, one of the most-highly studied genes in cancer research. First described in 1979, p53 is often described as the “guardian of the genome” because it sits in the center of a wide network of cellular processes to deal with DNA damage, and seems to tip the balance between repairing that damage and killing the cell. On the pro-repair side, p53 activates DNA repair proteins and halts the cell from its replicate-and-divide cycle until that it receives a signal that repair has been successful. However, if the damage proves to be too extensive, p53 will instead signal the cell to undergo apoptosis (a tightly-regulated death).

In almost all cases, tumor cells have lost functional p53 due to a mutation — otherwise, p53 would sense that something was wrong and get rid of those cells before they had a chance to grow uncontrollably. Thus, one aspect of Dr. Bargonetti’s research is to try to find drugs that can substitute in for p53: if p53 is gone but all of its targets (DNA repair proteins, etc.) still work normally, then a drug that goes around p53 directly to the target genes and activates them would be effective in killing those tumor cells.

Dr. Bargonetti also studies a second protein called MDM2. Healthy cells are constantly making p53 so that if there’s a problem, there’s a bunch already lying around to fix things. So, to keep p53 at constant levels, MDM2 is constantly tagging p53 to be degraded. These two proteins are kept in balance, so that p53 is being broken down and made at the same rate, keeping levels pretty constant. When there’s a problem, MDM2 gets blocked, allowing p53 to build up and do its job.

Dr. Bargonetti has found a connection between p53/MDM2 and estrogen in breast cancer — breast cancers that rely on estrogen for survival tend to have too much MDM2, while breast cancers that don’t rely on estrogen tend to have mutations in p53. She believes that further studying this pattern will help more clearly separate out different subtypes of breast cancer, for more targeted treatment.