fluorescently stained skin cancer sample

Tumor Initiation and Maintenance Program

Something goes wrong in a cell, sending it spinning out of control.


Our scientists study the types of cells that give rise to cancer and the molecular mechanisms they use to escape the normal cell cycle, including death. Their findings point the way to developing drugs that prohibit and inhibit tumor cell growth.


Singh DR, Pasquale EB, Hristova K
Biochim Biophys Acta 2016 Sep;1860(9):1922-8
Pasquale EB
J Cell Biol 2016 Jul 4;214(1):5-7
Claps G, Cheli Y, Zhang T, Scortegagna M, Lau E, Kim H, Qi J, Li JL, James B, Dzung A, Levesque MP, Dummer R, Hayward NK, Bosenberg M, Brown KM, Ronai ZA
Cell Rep 2016 May 31;15(9):1884-92
Mulvihill EE, Varin EM, Gladanac B, Campbell JE, Ussher JR, Baggio LL, Yusta B, Ayala J, Burmeister MA, Matthews D, Bang KW, Ayala JE, Drucker DJ
Cell Metab 2016 Nov 4;
Smith KR, Hussain T, Karimian Azari E, Steiner JL, Ayala JE, Pratley RE, Kyriazis GA
Am J Physiol Endocrinol Metab 2016 Feb 16;:ajpendo.00484.2015
Kim GH, Szabo A, King EM, Ayala J, Ayala JE, Altarejos JY
Mol Metab 2014 Dec 19;4(3):227-36

What is the focus of our program—What questions are we asking?

The TIM Program seeks to identify the cells that give rise to tumors and the signals that allow these cells to expand uncontrollably. Several members of the program focus on Stem Cells and Development, studying the stem cells that generate the brain, the mammary glands, the muscles and the skin, and how mutations transform these cells into cancer cells. Another major theme is Cell Growth Signaling, which includes investigation of the growth factors that cause cells to proliferate, and the proteins within cells that allow them to respond to these factors. Finally, several researchers in the program study RNA Biology, analyzing the ribonucleic acid (RNA) molecules that play key roles in regulating cell division, differentiation and survival.

How will our research help patients?

Members of the TIM program are elucidating the origins and molecular mechanisms of diseases, such as breast cancer, skin cancer and brain tumors. Their research not only deepens our understanding of these diseases, but also points the way toward novel approaches to therapy. Recent investigations in the program have: 

• Identified drugs that induce breast cancer cells to differentiate into normal cells.
• Discovered compounds that can divert signals in melanoma cells so they undergo cell death.
• Identified cell surface molecules that inhibit growth of glioblastoma.
• Shown new ways to target “cancer stem cells,” key cells within a tumor that are responsible for its long-term growth and malignancy.

In the long run these discoveries promise to improve outcomes for patients with these devastating diseases.