Zachary Schafer Coleman Foundation Associate Professor of Cancer Biology

Research Interests:

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:

• Mitophagy, oxidative stress, and sensitivity of cancer cells to therapy
• The relationship between the microenvironment and cancer cells
• Understanding links between metabolic reprogramming, cell death pathways, and oncogenic signaling
• Signal transduction involved in anoikis regulation

Biography:

• Assistant Department Chair, Department of Biological Sciences, University of Notre Dame; 2019-present
• Associate Professor of Biological Sciences, University of Notre Dame; 2015 - Present
• Coleman Foundation Collegiate Chair of Cancer Biology, University of Notre Dame; 2009 - Present
• Assistant Professor of Biological Sciences, University of Notre Dame; 2009 - 2015
• Postdoctoral Fellow, Department of Cell Biology, Harvard Medical School; 2006-2009
• Ph.D., Molecular Cancer Biology, Duke University; 2006 
• B.S., Biological Sciences, University of Notre Dame; 2001

Selected Papers:

• Joshua A. Mason, Jordan A. Cockfield, Daniel J. Pape, Hannah Meissner, Michael Sokolowski, Taylor C. White, José C. Valentín López, Juan Liu, Xioajing Liu, Inmaculada Martinez-Reyes, Navdeep S. Chandel, Jason W. Locasale, and Zachary T. Schafer. SGK1 signaling promotes glucose metabolism and survival in extracellular matrix detached cells. 2020. In revision. https://www.biorxiv.org/content/10.1101/2020.03.20.000463v1
• Yanting Luo, Louise Medina Bengtsson, Xuechun Wang, Tianhe Huang, Guoqiang Liu, Sean Murphy, Caiqin Wang, John Koren III, Zachary Schafer, and Xin Lu. UQCRH downregulation promotes Warburg effect in renal carcinoma cells. Sci Rep. 2020 Sep 14;10(1):15021. https://www.nature.com/articles/s41598-020-72107-2
• James H. Schofield and Zachary T. Schafer. Mitochondrial Reactive Oxygen Species and Mitophagy: A Complex and Nuanced Relationship. Antioxid Redox Signal. 2020 Apr 7. doi: 10.1089/ars.2020.8058. Online ahead of print. https://www.liebertpub.com/doi/10.1089/ars.2020.8058
• Mark A. Hawk, Cassandra L. Gorsuch, Patrick Fagan, Chan Lee, Sung Eun Kim, Jens C. Hamann, Joshua A. Mason, Kelsey J. Weigel, Matyas Abel Tsegaye, Luqun Shen, Sydney Shuff, Junjun Zuo, Stephan Hu, Lei Jiang, Sarah Chapman, W. Matthew Leevy, Ralph J. DeBerardinis, Michael Overholtzer, and Zachary T. Schafer. RIPK1-Mediated Induction of Mitophagy Compromises the Viability of Extracellular Matrix-Detached Cells. Nat Cell Biol. 2018 Mar; 20(3):272-284. https://www.nature.com/articles/s41556-018-0034-2,
  • Notre Dame press release
  • Nature Cell Biology Focus on Mitochondrial Form and Function
  • Faculty of 1000        
• Jordan A. Cockfield and Zachary T. Schafer. Antioxidant Defenses: A Context-Specific Vulnerability of Cancer Cells. Cancers. 2019 Aug 20;11(8):1208. https://www.mdpi.com/2072-6694/11/8/1208
• Mark A. Hawk and Zachary T. Schafer. Mechanisms of redox metabolism and cancer cell survival during extracellular matrix detachment. J Biol Chem. 2018 May 18;293(20):7531-7537
  https://www.jbc.org/content/293/20/7531.long
• Joshua A. Mason, Kimberly R. Hagel, Mark A. Hawk, and Zachary T. Schafer. Metabolism during ECM-Detachment: Achilles Heel of Cancer Cells? Trends Cancer. 2017 Jul;3(7):475-481 https://www.cell.com/trends/cancer/fulltext/S2405-8033(17)30086-9
• 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 Aug;23(8):1271-82 https://www.nature.com/articles/cdd201615
  • ​​​​​​​Notre Dame press release
• 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. https://www.nature.com/articles/nrc3789
• 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. https://www.jci.org/articles/view/62129
• 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. https://www.nature.com/articles/nature08268