Zachary Schug, Ph.D.

Zachary Schug, Ph.D.

  • Assistant Professor, Molecular and Cellular Oncogenesis
  • zschug@wistar.org
Summary

Alterations in the acquisition and metabolism of nutrients are now firmly recognized as hallmarks of cancer development. Many, if not all, oncogenes and tumor suppressor genes induce metabolic reprogramming in cancer cells through changes in the regulation of enzymes and transporters. These changes are necessary for cancer cells to meet the combined biomass and energy demands for growth and are only satisfied by increased capture and synthesis of cellular building blocks such as sugars, fats, and proteins. However, cancer cells often invade other tissues where the availability of certain nutrients is drastically different or grow so quickly that the blood supply, and the accessibility to oxygen and other nutrients that comes with it, becomes scarce. During these conditions of nutrient stress, many cancer cells will adapt and use other resources to survive.

In our lab, we are interested in investigating metabolic adaptation in cancer cells through the use of cell biology, biochemistry, and metabolomics. Metabolomics is the use of state-of-the-art analytical biochemistry and mass spectrometry to identify and quantify small molecules (or metabolites) in the body.

We seek to identify metabolic vulnerabilities in cancer that can be therapeutically exploited. We will combine metabolomics, systems biology, and genetics to uncover resistance mechanisms potentially created during metabolic adaptation to primary treatments. This complementary approach will help to identify effective combinatorial therapies during this era of precision medicine. Target validation will feed into an active drug discovery program aimed at inhibiting key metabolic enzymes in order to ultimately achieve a successful strategy for cancer treatment.

After completing his B.S. in Biology from Saint Joseph’s University, Zachary continued his studies in Philadelphia and earned a Ph.D. in Molecular Cell Biology from Thomas Jefferson University. In 2008 he began his post-doctoral studies at the Beatson Institute in Glasgow, United Kingdom and became a Research Assistant Professor during his time there. Zachary joined the Wistar Institute in 2016 as an Assistant Professor. 

Selected Publications

1. Peck B*, Schug ZT*, Zhang Q, Jones DT, Dankworth B, Smethurst E, Spencer-Dene B, Jiang M, Saunders R, Stamp G, Howell M, Alibhai D, Aboagye EO, Critchlow S, Harris AL, Wakelam MJO, Gottlieb E, Schulze A. Inhibition of Fatty Acid Desaturation is detrimental to cancer cell survival in metabolically compromised environments. Cancer Metab. Apr 1;4:6, 2016 *co-first author

2. Schug ZT, Vande Voorde J, Gottlieb E. The Metabolic Fate of Acetate in Cancer. Nat Rev Cancer. 2016. Invited Review.

3. Schug ZT, Peck B, Zhang Q, Jones DT, Grosskurth S,Alam IS, Smethurst E, Mason S, Blyth K, McGarry L, James D, Shanks E, Kalna G, Saunders B, Jiang M, Howell M, Lassailly F, Thin MZ, Spencer-Dene B, Stamp G, Harris AL, Aboagye EO,Critchlow SE, Wakelam MJO, Schulze A, Gottlieb E. Acetyl-coA Synthetase 2 Promotes Acetate Utilization and Maintains Cancer Cell Growth under Metabolic Stress. Cancer Cell. 27:57-71, 2015.

4. Patella F, Schug ZT, Persi E, Neilson LJ, Erami Z, Avanzato D, Maione F, Hernandez-Fernaud JR, Mackay G, L Zheng, Reid S, Frezza C, Giraudo E, Fiorio Pla A, Anderson K, Ruppin E, Gottlieb E, Zanivan S. Proteomics-based Metabolic Modelling Reveals that Fatty Acid Oxidation Controls Endothelial Cell Permeability. Mol Cell Proteomics. 14:621-34, 2015.

5. Witney TH, Pisaneschi F, Alam IS, Trousil S, Kaliszczak M, Twyman F, Brickute D, Nguyen QD, Schug ZT, Gottlieb E, Aboagye EO. Preclinical Evaluation of 3-18F-Fluoro-2,2-Dimethylpropionic Acid as an Imaging Agent for Tumor Detection. J Nucl Med. 55:1506-12, 2014.

6. Schug ZT, Frezza C, Galbraith LC, Gottlieb E. The music of lipids: how lipid composition orchestrates cellular behaviour. Acta Oncol. 51:301-10, 2012.

7. Schug ZT, Gonzalvez F, Houtkooper RH, Vaz FM and Gottlieb E. Bid is cleaved by caspase-8 within a native complex on the mitochondrial membrane. Cell Death Differ. 18:538-48, 2011.

8. Anyatonwu G, Khan MT, Schug ZT, da Fonseca P, Morris EP and Joseph SK. Calcium dependent conformational changes in inositol trisphosphate receptors. J Biol Chem. 285:25085-93, 2010.