Alexander V. Statsyuk Assistant Professor

Research Statement

Our research program is aimed at developing chemical tools to understand the ubiquitin system (E1, E2, E3 enzymes, and DUBs) for basic research and therapeutic purposes. Approximately 800 enzymes control the dynamic ubiquitination of ~19,000 protein substrates, and represent a vast and unexplored area of the human druggable genome. In addition to ubiquitin, ~20 other ubiquitin-like proteins exist that have specialized E1, E2, E3 enzymes and isopeptidases. Our research approaches include synthetic organic chemistry, protein chemistry, biochemistry, masspectrometry, and cell biology.

Selected Publications

Kathman, S.G.; Statsyuk, A.V. “Covalent tethering for covalent probe discovery”, MedChemComm, 2016, accepted.

An, H.; Statsyuk, A.V. “Rapid synthesis of electrophilic UBL-AMP probes to trap the reactive intermediates in E1-UBL-AMP ternary complexes”. Chemical Communications, 2016, 52, 2477-2480.

Kathman S.G.; Span I.; Smith A.T.; Xu, Z.Y.*; Zhan J.*; Rosenzweig A.C.; Statsyuk, A.V. “A Small Molecule That Switches a Ubiquitin Ligase From a Processive to a Distributive Enzymatic Mechanism”. J. Am. Chem. Soc. 2015, 137 (39), 12442-12445.

McShan, D.; Kathman S.G.; Lowe, B.; Xu, Z.Y.*; Zhan, J.*; Statsyuk, A.V.; Ogungbe, I.V. “Identification of non-peptidic cysteine reactive fragments as inhibitors of cysteine protease rhodesain”. Bioorg. Med. Chem. Lett. 2015, Oct 15; 25(20), 4509-12. (collaborative paper with Jackson State University).

Krist, D.T.; Statsyuk A.V. “Catalytically Important Residues of E6AP Ubiquitin Ligase Identified Using Acid-Cleavable Photo-cross-linkers”. Biochemistry 2015, 54 (29), 4411-4414.

An, H.; Statsyuk A.V. “An Inhibitor of Protein Ubiquitination and Agressome Formation”. Chemical Science 2015, 6, 5235-5245.

Park, S.; Krist, D.T.; Statsyuk, A.V. “Protein Ubiquitination and Formation of Polyubiquitin Chains without ATP, E1 and E2 Enzymes”. Chemical Science 2015, 6(3), 1770-1779.

Kathman, S.G.; Xu, Z.Y.*; Statsyuk, A.V. “A Fragment-Based Method to Discover Irreversible Covalent Inhibitors of Cysteine Proteases”. J. Med. Chem. 2014, 57 (11), 4969-74. Reviewed favorably by two popular drug discovery blogs: In the Pipeline, and Practical Fragments.

An, H.; Krist, D.T.; Statsyuk A.V. “Crosstalk between Kinases and Nedd4 Family Ubiquitin Ligases”. Mol. Biosyst. 2014, 10 (7), 1643-57. 2014 Emerging Investigators Edition.

An, H.; Statsyuk A.V. “Development of Activity-Based Probes for Ubiquitin and Ubiquitin-Like Protein Signaling Pathways”. J. Am. Chem. Soc. 2013, 135 (45), 16948-16962.

Hong, C.M.*; Statsuk, A.V. "The Development of a One Pot, Regiocontrolled, Three-Component Reaction for the Synthesis of Thieno[2,3-c]pyrroles". Organic & Biomolecular Chemistry 2013, 11(18), 2932-2935.
Note: Last name changed from Statsuk to Statsyuk.

Park, S.; Ntai, I.; Thomas, P.; Konishcheva, E.; Kelleher, N.L.; Statsuk, A.V. “Mechanism-Based Small Molecule Cross-Linkers of HECT E3 Ubiquitin-Ligase Substrate Pairs”. Biochemistry 2012, 51(42), 8327-8329.

Selected Honors/Awards

  • 2012-2013 Northwestern University Searle Teaching Fellow
  • 2012 Pew Scholar in Biomedical Sciences