Student's contribution to cancer research opening up new area for exploration
ARCS scholar Katy Van Hook, a PhD Candidate in the Charles Lopez Lab, likes to characterize cancer as a battle of "good versus evil."
"For me, that's what it really boils down to," said Katy, a student in the Cell & Developmental Biology graduate program, "with good tumor suppressors trying to keep cells in line and bad oncogene genes trying to break the rules and cause uncontrolled cell division."
Research in the Lopez lab focuses on a gene called p53, and how it functions to protect the cell. Known as a "tumor suppressor" gene, p53 plays a critical role in cellular stress response and is responsible for proteins that can either repair damaged cells, or cause damaged cells to die. Defects in the p53 pathway can lead to tumor formation, as well as resistance to therapy, which impacts the body's struggle to stave off cancer.
Katy's study is centered on the molecular mechanisms that promote p53-mediated tumor suppression. Specifically, she is focused on ASPP2—a p53-binding protein that promotes a type of protective cellular process known as apoptosis.
"Previous work by Dr. Lopez showed that ASPP2 is a tumor suppressor that promotes damage-induced apoptosis," said Katy. "It plays a critical role in maintaining the health of the body by eliminating old cells, unhealthy cells, and severely damaged cells, but spares the tissue and thus the organism."
The mechanisms of how ASPP2 protects cells from becoming cancerous, however, remain far from clear. Katy's job is to investigate its function and determine if it might be relevant in human cancer.
During her research, Katy made the important discovery of a novel ASPP2 isoform (deltaN-ASPP2), which is structurally very similar to ASPP2 but truncated and thus smaller. Despite their structural similarity, ASPP2 and deltaN-ASPP2 appear to have opposite functions, with ASPP2 promoting the elimination of "bad" cells and deltaN-ASPP2 promoting their survival.
Importantly, Katy found that this isoform is overexpressed in breast tumors—suggesting that it may be an oncogene that plays a central role in promoting breast cancer as well as poor therapy response.
"This has been a technically very challenging project," said Charles Lopez, MD, PhD, Associate Professor, Department of Medicine. "However, Katy's perseverance and tenacity has resulted in her generating some provocative findings—and I am pleased to see her hard work begin to open up completely new areas for exploration in this field."
Katy recently presented her findings at the 2011 American Association of Cancer Research annual meeting, and is in the process of writing her work up for publication.
After receiving her degree this summer, Katy will search for a post-doctoral position that allows her to expand her understanding of cancer development, progression, and treatment while allowing her the opportunity to mentor and teach younger scientists.
Pictured above: Katy Van Hook and Charles Lopez, MD, PhD