Zachary Schafer Coleman Foundation Associate Professor of Cancer Biology
Metastasis, the spread of cancer from the site of the primary tumor to distant locations in the body, is responsible for 90% of cancer deaths, yet the molecular mechanisms governing this extraordinarily complicated process remain poorly understood. It has become clear that an important barrier to metastasis is the induction of anoikis, a cell death process that is induced when epithelial cells lose attachment to the extracellular matrix (ECM). During the course of tumor progression, cancer cells will typically acquire resistance to anoikis which can facilitate the spread of these cells to distant sites. In addition to the induction of the anoikis program, we have discovered that ECM-detached cells are metabolically compromised in a fashion that prohibits their survival. Thus, ECM-detached cancer cells need to inhibit anoikis and rectify their metabolic deficiencies in order to survive. Despite its importance, there is a striking lack of information on how cancer cells successfully evade the induction of anoikis and overcome metabolic deficiencies. The overarching goal of my laboratory is to examine and characterize the biological mechanisms that permit cancer cell survival in the absence of ECM attachment. It is our hope that a better understanding of these mechanisms at the molecular level will reveal novel chemotherapeutic targets or approaches that may serve to compromise the survival of ECM-detached cancer cells and thus prevent tumors from successfully metastasizing.
We have 4 distinct, major research projects in the lab that are all aimed at achieving the aforementioned overarching goal:
- The role of ROS in the survival of ECM-detached breast cancer cells
- CAF-mediated inhibition of anoikis in breast cancer cells
- Tumor cell survival in inflammatory breast cancer
- Oncogenic signaling involved in anoikis regulation
- Coleman Assistant Professor of Cancer Biology, University of Notre Dame
- Postdoctoral Fellow, Department of Cell Biology, Harvard Medical School
- Ph.D., Molecular Cancer Biology, Duke University
- B.S., Biological Sciences, University of Notre Dame
- Joshua A. Mason and Zachary T. Schafer. SGK-1 and PHLPP1: Ras-mediated effectors during ECM-detachment. Cell Cycle. 2016 In press.
- Joshua A. Mason, Calli A. Davison-Versagli, Amy K. Leliaert, Daniel J. Pape, Chelsea McCallister, Junjun Zuo, Sienna M. Durbin, Cassandra L. Buchheit, Siyuan Zhang, and Zachary T. Schafer. Oncogenic Ras differentially regulates metabolism and anoikis in extracellular matrix-detached cells. Cell Death Differ. 2016 Feb 26.
- Raju R. Rayavarapu, Brendan Heiden, Nicholas Pagani, Sydney Shuff, Siyuan Zhang, and Zachary T. Schafer. The Role of Multicellular Aggregation in the Survival of ErbB2-Positive Breast Cancer Cells during Extracellular Matrix-Detachment. J Biol Chem. 2015 Apr 3;290(14):8722-33. Featured as Cover article: April 3, 2015 issue.
- Kelsey J. Weigel, Luqun Shen, Clayton L. Thomas, Daniel Alber, Lauren Drapalik, Zachary T. Schafer, Shaun W. Lee. Design and evaluation of a peptide-based immunotoxin for breast cancer therapeutics. FEBS Open Bio. 2015 Mar 14;5:202-8
- Cassandra L. Buchheit and Zachary T. Schafer. Bim-EL localization: The key to understanding anoikis resistance in inflammatory breast cancer cells. Mol Cell Oncol. 2015 3:1. e1011474; November 2015.
- Cassandra L. Buchheit, Brittany L. Angarola, Allison Steiner, Kelsey J. Weigel, and Zachary T. Schafer. Anoikis evasion in inflammatory breast cancer cells is mediated by Bim-EL sequestration. Cell Death Differ. 2015 Aug; 22(8): 1275-86. Epub 2014 Dec 19.
- Cassandra L. Buchheit, Kelsey J. Weigel, and Zachary T. Schafer. Cancer Cell Survival During ECM-Detachment: Multiple Barriers to Tumor Progression. Nat Rev Cancer. 2014 Sep;14(9):632-41.
- Kelsey J. Weigel, Ana Jakimenko, Brooke A. Conti, Sarah E. Chapman, William J. Kaliney, W. Matthew Leevy, Matthew M. Champion, and Zachary T. Schafer. CAF-Secreted IGFBPs Regulate Breast Cancer Cell Anoikis. Mol Cancer Res. 2014 Jun; 12(6): 855-66. Featured in Mol Cancer Res. 2014 Jun; 12(6): 813.
- Calli A. Davison, Sienna M. Durbin, Matthew R. Thau, Victoria R. Zellmer, Sarah E. Chapman, Justin Diener, Connor Wathen, W. Matthew Leevy, and Zachary T. Schafer. Antioxidant Enzymes Mediate Survival of Breast Cancer Cells Deprived of Extracellular Matrix. Cancer Res. 2013 Jun 15; 73(12): 3704-15. Cited in Faculty of 1000
- Calli A. Davison, Sarah E. Chapman, Todd A. Sasser, Connor Wathen, Justin Diener, Zachary T. Schafer, and W. Matthew Leevy. Multimodal Optical, X-ray CT, and SPECT Imaging of a Mouse Model of Breast Cancer Lung Metastasis. Curr Mol Med. 2013 Mar 1; 13(3): 368-76.
- Keisuke Ito, Arkaitz Carracedo, Dror Weiss, Fumio Arai, Ugo Ala, David E. Avigan, Zachary T. Schafer, Ronald M. Evans, Toshio Suda, Chih-Hao Lee, and Pier Paolo Pandolfi. A PML-PPARδ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance. Nat Med. 2012 Sep; 18 (9):1350–1358. Featured in Nat Med. 2012 Sep; 18 (9): 1334–1336.
- Arkaitz Carracedo, Dror Weiss, Amy K. Leliaert, Manoj Bhasin, Vincent C. J. deBoer, Gaelle Laurent, Andrew Adams, Maria Sundvall, Su Jung Song, Keisuke Ito, Lydia S. Finley, Ainara Egia, Towia Libermann, Zachary Gerhart-Hines, Pere Puigserver, Marcia C. Haigis, Elefteria Maratos-Flier, Andrea L. Richardson, Zachary T. Schafer, and Pier P. Pandolfi. A metabolic prosurvival role for PML in breast cancer. J Clin Invest. 2012 Sep 4;122(9):3088-100.
- Zachary T. Schafer and Leta K. Nutt. Understanding Tumor Cell Metabolism: The Secret to Winning the War (burg) on Cancer? Semin Cell Dev Biol. 2012 Jun;23(4):351.
- Cassandra L. Buchheit, Raju Rayavarapu, and Zachary T. Schafer. The Regulation of Cancer Cell Death and Metabolism by Extracellular Matrix Attachment. Semin Cell Dev Biol. 2012 Jun;23(4):402-11