Cellular and Signaling Network Cross-Talk in Ovarian Cancer
Ovarian cancer has a mortality rate of greater than 50%, primarily due to the late stage at which it is diagnosed. This late diagnosis complicates treatment – patients accumulate different mutations in their tumors and tumor cells receive a variety of stimuli from other cell types during disease progression, making it impossible to define a blanket treatment for everyone. We are working to address this complex scenario through several complementary approaches. First, we are characterizing a panel of ovarian cancer cell lines to capture this diversity and determine how cells respond to current drugs. By delineating molecular signatures that correspond to drug sensitivities we hope to better match patients to drugs and improve prognosis. Secondly, we are examining cross-talk between signaling pathways in the tumor cell to determine signals that are responsible for controlling proliferation, providing new drug targets for ovarian cancer. Finally, we are developing in vitroculture systems to study interactions between ovarian cancer tumor cells and other cells in the tumor microenvironment in order to identify new approaches to control tumor growth.
Cellular Decision-Making Processes in Wound Healing and Angiogenesis
Tissue engineers are working to develop methods to restore or improve tissue function, largely through a process of trial and error. In contrast, we are working to determine design principles to inform the creation of tissue engineering scaffolds. In collaboration with Prof. Kristyn Masters, we are characterizing how keratinocytes and endothelial cells interpret, integrate, and respond to simple and complex combinations of microenvironmental cues. In particular, we are examining the link between environmental cues, the downstream signaling events that result, and cellular responses. By identifying this relationship, we will be able to identify combinations of stimuli that promote desirable behaviors such as increased migration for wound healing or increased tubule formation for angiogenesis.
Honors & Awards
- 2014 NIH New Innovator
- 2014 Cellular and Molecular Bioengineering Young Innovator
- 2014 Chemical Communications Emerging Investigator
- 2013 James G. Woodburne Award for Excellence in Teaching
- 2013 American Cancer Society Research Scholar
- 2010 NSF CAREER Award
- 2008 American Cancer Society Postdoctoral Fellowship
- Technician – Anthony Desotell
- Post-doc – Lisa Wickert
- Grad students – Anthony Berger, Danielle Bourgeois, Molly Carroll, Andy Fleszar, Chloe Kim, Harris Krause
Selected Publications (Find recent publications on PubMed)
- D Tian, P Rajbhandari, K Bjorkland, NM Solodin, ET Alarid, PK Kreeger. A kinetic model identifies phosphorylated estrogen receptor-α (ERα) as a critical regulator of ERα dynamics in breast cancer. FASEBJ. 29: 5, p. 2022-2031, 2015.
- D Tian, PK Kreeger. “Analysis of the quantitative balance between insulin-like growth factor (IGF)-1 ligand, receptor, and binding protein levels to predict cell sensitivity and therapeutic efficacy.” BMC Systems Biology. 8: 98, 2014.
- MJ Carroll, LE Stopfer, PK Kreeger. “A simplified culture system to examine soluble factor interactions between mammalian cells.”Chemical Communications. 50, p. 5279-5281, 2014.
- PK Kreeger. “Using partial least squares regression to analyze cellular response data.” Science Signaling. 6, p. tr7, 2013.
- RD Prasasya, KZ Vang, PK Kreeger. “A multivariate model of ErbB network composition predicts ovarian cancer cell response to canertinib.” Biotechnology and Bioengineering. 109, p. 213-224, 2012.