Cancer Cell Biology and Metabolism
Zachary T. Schafer
Coleman Assistant Professor of Cancer Biology
B.S., University of Notre Dame
Ph.D., Duke University
Postdoctoral fellow, Harvard Medical School
Office: 222 Galvin Life Science Center
Lab: 225 & 226 Galvin Life Science Center
Office Phone: (574) 631-0875
Lab Phone: (574) 631-3228
The current approaches for the treatment and prevention of cancer are often inadequate due to their inability to selectively kill tumor cells without affecting non-cancerous cells. In order to obtain the necessary specificity in chemotherapeutic approaches, it is critical to understand the basic biological processes governing normal and tumor cell survival; an area of research where much remains to be discovered.
My laboratory studies how cancer cells can survive outside their natural niches and how changes in cellular metabolism can promote survival or induce cell death. Our previous research has uncovered evidence that oxidative stress can be tumor suppressive by killing cells that are not in their natural environment (i.e. in the luminal space of a mammary acinus, see Figure 1 below). In addition, we have found that oncogenes promote anchorage independent survival of tumor cells by altering their metabolism in a manner that reduces oxidative stress. These data identify the extracellular matrix (ECM) as a critical regulator of cell metabolism and raise the possibility that antioxidants may have pro-tumorigenic properties in addition to their well described anti-tumorigenic effects.
My laboratory is currently focusing on 3 primary questions related to these findings:
1. What are the metabolic changes induced by epithelial cell detachment from the extracellular matrix that affect cell survival?
These studies include both targeted approaches and more global approaches to better understand detachment-induced changes in metabolism and aim to elucidate the molecular mechanisms governing these alterations.
2. How do detachment-induced metabolic changes affect tumorigenesis?
These studies focus specifically on understanding how detachment-induced metabolic changes (i.e. ATP deficiency) affect the transformation of epithelial cells. We use a combination of approaches including standard cell culture, 3D cell culture, soft agar assays, and xenograft models to examine metabolic alterations in a variety of cell types and contexts.
3. How does antioxidant treatment or activity affect tumorigenesis?
Our research has revealed that antioxidants may promote the survival of tumor cells in certain contexts and potentially enhance tumor formation. We are currently using both 2D and 3D cell culture models to expand upon our previous antioxidant studies with the goal of better understanding the relationship between oxidative stress and the survival of tumor cells outside their natural niche.
Zachary T. Schafer, Alexandra R. Grassian, Loling Song, Zhenyang Jiang, Zachary Gerhart-Hines, Hanna Y. Irie, Sizhen Gao, Pere Puigserver, and Joan S. Brugge. Antioxidant and Oncogene Rescue of Metabolic Defects Caused by Loss of Matrix Attachment. Nature. 2009 Sep 3;461(7260):109-13.
Zachary T. Schafer and Joan S. Brugge. IL-6 Involvment in Epithelial Cancers. J. Clin. Invest. 2007; 117: 3660-3663.
Zachary T. Schafer and Sally Kornbluth. The Apoptosome: Phyiological, Developmental, and Pathological Modes of Regulation. Dev Cell. 2006 May; 10(5): 549-561.
Zachary T. Schafer, Amanda B. Parrish, Kevin M. Wright, Seth S. Margolis, Jeffrey R. Marks, Mohanish Deshmukh, and Sally Kornbluth. Enhanced Sensitivity to Cytochrome c-Induced Apoptosis Mediated by PHAPI in Breast Cancer Cells. Cancer Res. 2006 Feb 15; 66(4): 2210-2218.
Paula B. Deming,* Zachary T. Schafer,* Jessica S. Tashker, Malia B. Potts, Mohanish Deshmukh, and Sally Kornbluth. Bcr-Abl-Mediated Protection from Apoptosis Downstream of Mitochondrial Cytochrome c Release. Mol Cell Biol. 2004 Dec; 24(23):10289-10299.
*Co-equal first authors.