Prof. Stanislav Engel Profile

Prof. Stanislav Engel

Associate Professor
PhD 2004

Researcher

Department :	Clinical Biochemistry and Pharmacology
Room :	322 בנין המכון למחקר ישומי במדעי החיים ע"ש דה 39-פיצ'וטו
Phone :	972-74-7728593 972-74-7728594
Email :	engels@bgu.ac.il
Office Hours :

Education

B.Sc. 1993-1997: The Dept. of Life Sciences, Ben-Gurion University, Beer-Sheva, Israel
M.Sc. 1998-2000: The Dept. of Biotechnology Engineering, Ben-Gurion University, Israel
Ph.D. 2000-2004: The Dept. of Biotechnology Engineering, Ben-Gurion University, Israel
Postdoctoral Training. 2004-2009: Molecular pharmacology and Molecular modeling, Drug discovery program. Clinical Endocrinology Branch and Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA

Research Interests

Misfolded SOD1 as a target in Amyotrophic Lateral Sclerosis (ALS) drug discovery.
Structural basis of GPCR signal transduction.
Protein/protein and protein/small-molecule interactions.
Targeting protein/protein interfaces by drugs.
Identification of biologically active compounds using in vitro selection methods.
Computer-aided drug discovery.

Research Projects

Misfolded SOD1 gain-of-function as a target in Amyotrophic Lateral Sclerosis (ALS) drug discovery.
Functional mimetics of the extra- and intracellular domains of G protein coupled receptors (GPCR) as a tool for studying the structural basis of GPCR interaction with molecular targets and drug discovery.
In vitro selection methods to identifying active compounds targeting protein-protein interactions.
Molecular modeling in structure-based drug discovery.

Publications and funding summary / representative publications and grants

1. Bakavayev S, Argueti S, Venkatachalam N, Yehezkel G, Stavsky A, Barak Z, Israelson A, and Engel S. Exposure of b6/b7-Loop in Zn/Cu Superoxide Dismutase (SOD1) Is Coupled to Metal Loss and Is Transiently Reversible During Misfolding. 2020, doi: 10.1021/acschemneuro.0c00524

2. Venkatachalama N, Bakavayev S, Engel D, Barak Z, Engel S. Primate differential redoxome (PDR) – A paradigm for understanding neurodegenerative diseases. Redox Biology. 2020, 36, 101683. doi: 10.1016/j.redox.2020.101683

3. Bakavayev S, Chetrit N, Zvagelsky T, Mansour R, Vyazmensky M, Barak Z, Israelson A, Engel S. Cu/Zn-superoxide dismutase and wild-type like fALS SOD1 mutants produce cytotoxic quantities of H2O2 via cysteine-dependent redox short-circuit. Sci Rep. 2019, 9(1):10826. doi: 10.1038/s41598-019-47326-x.

4. Banerjee V, Oren O, Dagan B, Taube R, Engel S, Papo N. An Engineered Variant of the B1 Domain of Protein G Suppresses the Aggregation and Toxicity of Intra- and Extracellular Abeta-42. ACS Chem Neurosci. 2019, 10(3):1488-1496. doi: 10.1021/acschemneuro.8b00491.

5. Kuttner YY, Engel S. Complementarity of stability patches at the interfaces of protein complexes: Implication for the structural organization of energetic hot spots. Proteins. 2018, 86(2):229-236. doi: 10.1002/prot.25430.

6. Shvil N, Banerjee V, Zoltsman G, Shani T, Kahn J, Abu-Hamad S, Papo N, Engel S, Bernhagen J, Israelson A. MIF inhibits the formation and toxicity of misfolded SOD1 amyloid aggregates: implications for familial ALS. Cell Death Dis. 2018, 9(2):107. doi: 10.1038/s41419-017-0130-4.

7. Banerjee V, Oren O, Ben-Zeev E, Taube R, Engel S, Papo N. A computational combinatorial approach identifies a protein inhibitor of superoxide dismutase 1 misfolding, aggregation, and cytotoxicity. J Biol Chem. 2017, 292(38):15777-15788. doi: 10.1074/jbc.M117.789610.

8. Press O, Zvagelsky T, Vyazmensky M, Kleinau G, Engel S. Construction of Structural Mimetics of the Thyrotropin Receptor Intracellular Domain. Biophys J. 2016, 111(12):2620-2628. doi: 10.1016/j.bpj.2016.11.002.

9. Banerjee V, Shani T, Katzman B, Vyazmensky M, Papo N, Israelson A, Engel S. Superoxide Dismutase 1 (SOD1)-Derived Peptide Inhibits Amyloid Aggregation of Familial Amyotrophic Lateral Sclerosis SOD1 Mutants. ACS Chem Neurosci. 2016, 7(11):1595-1606. doi: 10.1021/acschemneuro.6b00227.

10. Osman R, Mezei M, Engel S. The role of protein "Stability patches" in molecular recognition: A case study of the human growth hormone-receptor complex. J Comput Chem. 2016, 37(10):913-9. doi: 10.1002/jcc.24276.

11. Kuzmina A, Vaknin K, Gdalevsky G, Vyazmensky M, Marks RS, Taube R, Engel S. Functional Mimetics of the HIV-1 CCR5 Co-Receptor Displayed on the Surface of Magnetic Liposomes. PLoS One. 2015;10(12):e0144043. doi: 10.1371/journal.pone.0144043. eCollection 2015.

12. Katzman B, Vyazmensky M, Press O, Volokita M, Engel S. Tethered ribozyme ligation enables detection of molecular proximity in homogeneous solutions. Biotechnol J. 2015, 10(3):379-85. doi: 10.1002/biot.201400551.

13. Kuttner YY, Nagar T, Engel S. Surface dynamics in allosteric regulation of protein-protein interactions: modulation of calmodulin functions by Ca2+. PLoS Comput Biol. 2013, (4):e1003028. doi: 10.1371/journal.pcbi.1003028.

14. Kuttner YY, Engel S. Protein hot spots: the islands of stability. J Mol Biol. 2012, 415(2):419-28. doi: 10.1016/j.jmb.2011.11.009.

15. Engel S, Skoumbourdis AP, Childress J, Neumann S, Deschamps JR, Thomas CJ, Colson AO, Costanzi S, Gershengorn MC. A virtual screen for diverse ligands: discovery of selective G protein-coupled receptor antagonists. J Am Chem Soc. 2008, 130(15):5115-23. doi: 10.1021/ja077620l.

16. Engel S, Gershengorn MC. Thyrotropin-releasing hormone and its receptors--a hypothesis for binding and receptor activation. Pharmacol Ther. 2007, 113(2):410-9. doi: 10.1016/j.pharmthera.2006.09.004.

17. Engel S, Neumann S, Kaur N, Monga V, Jain R, Northup J, Gershengorn MC. Low affinity analogs of thyrotropin-releasing hormone are super-agonists. J Biol Chem. 2006, 281(19):13103-9. doi: 10.1074/jbc.M600440200. Epub 2006 Mar 21. PubMed PMID: 16551618.

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