The Keystone Program in Epigenetics and Progenitor Cells

The Potential

“This program has the strong potential to be a ‘Top 5’ national program due to the importance of the topic and the strong foundation of these areas at Fox Chase and in Philadelphia.” – Keystone Programs External Review Panel

Current Projects

The Keystone Program in Epigenetics and Progenitor Cells was established in 2008. Since then, the program has created and funded five pilot research projects and hired a full-time post-doctoral researcher for each project. Importantly, the program has recruited two new junior faculty researchers, Drs. Andy Andrews and Zeng-jie Yang, who are poised to become leaders in the fields of epigenetics and stem cell biology, respectively. The program is organizing an international symposium on Cancer Epigenetics and Progenitor Cells to take place in the spring of 2012.

Progress in the fight against cancer depends on collaboration between disciplines. Laboratory scientists need the experience of clinicians who treat patients with cancer and clinicians need the insight of basic scientists who are working on the fundamental causes of cancer. To bring disciplines together and develop new collaborations, Keystone Program researchers meet every week to present progress reports and discuss new ideas.

The researchers form interdisciplinary teams and work together to find answers to fundamental scientific questions. Based on early research results, Keystone Program leaders will select the most promising pilot studies for additional funding.

Current questions being explored include:

1. What happens when we turn off epigenetic tags on DNA in cancer cells?
• Using a chemical inhibitor, Keystone scientists removed epigenetic tags on DNA in cultures of metastatic melanoma cells. Once the epigenetic tags were removed, normal cell differentiation genes were expressed and the cells began dividing normally.


2. How is the Notch signaling pathway involved?
• Abnormal expression of genes in the Notch pathway plays a role in the development of cancer. Keystone scientists found that turning off expression of a tumor suppressor gene in mouse neural stem cells increased Notch gene activity.


3. How do cells restore epigenetic marks after they divide?
• Before a cell divides in a process called mitosis, its DNA must be tightened and condensed. Epigenetic tags are erased during this process. After the cell divides, each cell re-sets its original epigenetic tags, but scientists have no idea how this happens. To find out, Keystone scientists are identifying genes that are expressed in cancer cells during cell differentiation. The goal is to identify and create a database of epigenetic marker genes and learn how they work together to regulate development of cancer cells.


4. Which genes control intestinal stem cell proliferation?
• Keystone scientists are studying a tumor suppressor gene called p16 that regulates the division of intestinal stem cells in mammals. Silencing p16 leads to colon cancer. The scientists have created a new type of transgenic mouse to study how activating p16 affects intestinal stem cells and the development of colitis and colon cancer.


5. How is DNA repair related to epigenetic changes?
• Cancer cells often have defects in DNA repair genes. Keystone scientists developed a strain of mice with inactive DNA repair genes and discovered that the same genes are active during embryonic development in mice. Learning how these genes work during early development could help scientists learn how to repair damaged genes.