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Profile: Alexander Statsyuk

Alexander Statsyuk
Alexander V. Statsyuk, Ph.D.
Assistant Professor of Medicinal Chemistry

Health 2
University of Houston College of Pharmacy
4849 Calhoun Road, Room 7037
Houston, TX 77204-5037

Office: 713-743-9616
Fax: 713-743-1884


Ph.D. in Organic Chemistry, University of Chicago, Chicago, Illinois

Diploma in Chemistry, Lomonosov Moscow State University, Moscow, Russia

Research Interests

Chemical Biology of the Ubiquitin System and Autophagy

Our research program is aimed at developing chemical tools to understand the ubiquitin system (E1, E2, E3 enzymes, and DUBs) and autophagy for basic research and therapeutic purposes. The ubiquitin system and autophagy are evolutionarily conserved degradation systems that control protein/organelle function and quality.

To this end, we study the mechanism of ubiquitin and autophagy enzymes, and then develop mechanism-based pharmacological probes to perturb the function of these enzymes. This allows us to uncover novel biological roles of these enzymes, to validate them as drug targets, and to initiate drug-discovery programs. 

Research Support

Active Grants

Title: Autophagy inhibitors to prevent nutrient supply and organelle and proteome quality control in K-Ras and B-Raf driven cancers
Source: William & Ella Owens Medical Research Foundation
Role: Principal Investigator
Dates: 01/01/2017-12/31/2018
Total Costs: $205,000

Title: Pharmacological Inhibitors of Nedd4 Ubiquitin Ligase as Anticancer Therapeutics
Source: NIH (1R01GM115632)
Role: Principal Investigator
Dates: 07/01/15–06/30/20
Total Costs: $1,429,602

Title: Using Chemical Genetics to Discover New Physiological Functions of the Ubiquitin System
Source: The Pew Charitable Trusts Class of 2012 Pew Biomedical Scholars Program
Role: Principal Investigator
Dates: 08/01/12–07/31/17
Total Costs: $240,000

Title: Bypassing the Native Ubiquitination Cascade to Develop Parkin Inhibitors and Activators
Source: The Michael J. Fox Foundation for Parkinson’s Research
Role: Co-PI; Rice (PI)
Dates: 07/01/15–06/30/16
Direct Costs: $100,000

Completed Research Support

Title: Transforming the Future: Targeting the Ubiquitin System to Treat Ewing’s Sarcoma
Source: Robert H. Lurie Comprehensive Cancer Center H Foundation, H Foundation Pilot Project
Role: Principal Investigator
Dates: 05/01/15–05/31/16
Direct Costs: $10,000

Title: Targeting the Ubiquitin System: Nedd4-1 Ubiquitin Ligase as a Promising Drug Target To Treat Ebola Virus Infections, Parkinson’s Disease, and IGF-1 Receptor Driven Human Cancers
Source: Chemistry of Life Processes Institute at Northwestern University, Cornew Innovation Award
Role: Principal Investigator
Dates: 12/01/14–11/30/15
Direct Costs: $50,000

Title: Targeting Nedd4-1 Ubiquitin Ligase to Treat Ewing Sarcoma
Source: American Cancer Society Institutional Research Grant
Role: Statsyuk (Project PI); Platanias (IRG PI)
Dates: 01/01/15–12/31/15
Direct Costs: $30,000

Title: High-Throughput screening of Nedd4-1 inhibitors using the novel probe: Ub-Flu
Source: Searle Funds at The Chicago Community Trust | Chicago Biomedical Consortium
Role: Principal Investigator
Dates: 07/01/15–06/30/16
Direct Costs: $20,000

Lab Members

Postdoctoral fellows

Sandipan Roy Chowdhury
B.S., Presidency College, University of Calcutta, 2007
M.S., Indian Institute of Technology (IIT), Kharagpur, 2009
Ph.D., Arizona State University, 2016

Steven Kennedy
B.S., University of Tulsa, 2008
Ph.D. University of Tulsa, 2013
Postdoctoral Fellow, Structural Genomics Consortium, 2013-2016

Graduate Students

Patrick Chuong
B.S., UCSD, 2015

Pharmacy Students

Ngan Nguyen
Pharm.D., University of Houston College of Pharmacy, Class of 2021

Undergraduate Students

Akshat Kumar
B.S., University of Houston, 2020 expected

Alyssa Nguyen
B.S., University of Houston, 2018, expected

Lab Alumni

Peter Foote
B.A., Amherst College, 2009
Ph.D., Northwestern University, 2016
Currently Scientist, Lifesensors

Stefan Kathman
B.A., Harvard University, 2009
Ph.D., Northwestern University, 2016
Currently postdoc in Benjamin Cravatt research group, Scripps Research Institute

David Krist
B.A. Grinnell College, 2008
Ph.D., Northwestern University, 2016
Currently with the Schulman Lab, Max Plank, Munich, Germany

Sungjin Park
B.S., Hanyang University, 2003
M.S. Hanyang University, 2005
Ph.D., Univ of North Carolina Chapel Hill, 2010
Postdoc in Statsyuk and Rice labs, 2010-2016
Currently CEO of OneGene Biotechnology, Korea

Heeseon An
B.S., Seoul National University, 2006
M.S., Seoul National University, 2008
Ph.D., Northwestern University, 2015
Currently with The Harper Lab, Harvard Medical School, Harvard University

Galyah Boneh
B.A., University of Colorado at Boulder, 2011
M.S., Northwestern University, 2017

Ziyang Xu
B.S., Northwestern University, 2015
Currently MD/PhD Candidate, University of Pennsylvania

Jeromy Gotschall
Northwestern University Class of 2018

Zayn Raza Tajamal
Northwestern University Class of 2016

Kristen Sanders
B.S., University of Arizona, 2011
M.S. Northwestern University, 2013

Cynthia Hong
B.S., Northwestern University, 2013
Currently with The Toste Group, UC Berkeley

Pradeep Bugga
B.S., California Institute of Technology, 2009
Currently with Mrksich Research Group, Northwestern University

Fangke Xu
B.S., Purdue University, 2011
IBIS Rotation Student
Currently with The Allada Lab, Northwestern University

Evgeniya Konishcheva
Moscow State University '12 chemistry major
Currently at University of Basel

Jennifer Zhan
B.S., Northwestern University, 2016

Lauren Abruzzo
B.S., Northwestern University, 2017

Selected Publications

Olp MD, Sprague DJ, Goetz CJ, Kathman SG, Wynia-Smith SL, Shishodia S, Summers SB, Xu Z, Statsyuk AV, Smith BC. Covalent-Fragment Screening of BRD4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites. ACS Chem Biol. 2020 Apr 17;15(4):1036-1049. doi: 10.1021/acschembio.0c00058. Epub 2020 Mar 23.

Parker BW, Goncz EJ, Krist DT, Statsyuk AV, Nesvizhskii AI, Weiss EL. Mapping low-affinity/high-specificity peptide-protein interactions using ligand-footprinting mass spectrometry. Proc Natl Acad Sci U S A. 2019 Oct 15;116(42):21001-21011. doi: 10.1073/pnas.1819533116. Epub 2019 Oct 2.

Kathman SG, Statsyuk AV. Methodology for Identification of Cysteine-Reactive Covalent Inhibitors. Methods Mol Biol. 2019;1967:245-262. 

Chowdhury SR, Kennedy S, Zhu K, Mishra R, Chuong P, Nguyen AU, Kathman SG, Statsyuk AV. Discovery of covalent enzyme inhibitors using virtual docking of covalent fragments. Bioorg Med Chem Lett. 2019 Jan 1;29(1):36-39.

Ramirez YA, Adler TB, Altmann E, Klemm T, Tiesmeyer C, Sauer F, Kathman SG, Statsyuk AV, Sotriffer C, Kisker C. Structural Basis of Substrate Recognition and Covalent Inhibition of Cdu1 from Chlamydia trachomatis. ChemMedChem. 2018 Oct 8;13(19):2014-2023.

Foote PK, Statsyuk AV. Monitoring PARKIN RBR Ubiquitin Ligase Activation States with UbFluor. Curr Protoc Chem Biol. 2018 Sep;10(3):e45.

Statsyuk AV. Let K-Ras activate its own inhibitor. Nat Struct Mol Biol. 2018 Jun;25(6):435-437.

Katrin Juenemann, Anne Jansen, Luigi van Riel, Remco Merkx, Monique Mulder, Heeseon An, Alexander V. Statsyuk, Janine Kirstein, Huib Ovaa, and Eric Reits, "Dynamic recruitment of ubiquitin to mutant huntingtin inclusion bodies", Scientific Reports, Sci. Rep. 2018 Jan 23;8(1):1405.

Krist, D.T.; Foote, P.; Statsyuk, A.V. UbFluor: A Fluorescent Thioester to Monitor RBR E3 Ligase Catalysis. Current Protocols in Chemical Biology, 2017 Mar 2;9(1):11-37.

Krist, D.T.; Foote, P.; Statsyuk, A.V. High-throughput screening for HECT E3 ligases using UbFluor. Current Protocols in Chemical Biology, 2017, 14, 9(3):174-195.

Park S, Foote PK, Krist DT, Rice SE, Statsyuk AV. UbMES and UbFluor: Novel Probes For RBR E3 Ubiquitin Ligase PARKIN. J. Biol. Chem. 2017, 292 (40):16539-16553.

Misra M, Kuhn M, Löbel M, An H, Statsyuk AV, Sotriffer C, Schindelin H. Dissecting the Specificity of Adenosyl Sulfamate Inhibitors Targeting the Ubiquitin-Activating Enzyme. Structure. 2017, 25(7):1120-1129.e3.

Krist, D.T.; Foote, P.; Statsyuk, A.V., "The Use of Ubfluor to Monitor HECT E3 Ligase Activity." Curr. Protoc. Chem. Biol., 2017 Mar 2;9(1):11-37. doi: 10.1002/cpch.17.

Krist, D.T.; Park, S.; Boneh, G.; Rice, S.; Statsyuk, A.V., "UbFluor: A Mechanism-Based Probe for HECT E3 Ligases." Chemical Science, 2016, 7, 5587-5595.

Kathman, S.G.; Statsyuk, A.V., "Covalent Tethering of Fragments for Covalent Probe Discovery." MedChemComm, 2016, 7, 576-585. PMCID: PMC4933313

An, H.; Statsyuk, A.V., "Facile Synthesis of Covalent Probes to Capture Enzymatic Intermediates during E1 Enzyme Catalysis." Chemical Communications, 2016, 52, 2477-2480

Kathman, S.G.; Span, I.; Smith, A.; 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." Biorg Med Chem Lett 2015, Oct 15;25(20), 4509-12.

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 Ubiquitin Conjugation and Aggresome 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, 1770-1779.

Kathman, S.G.; Xu, Z.Y.; Statsyuk, A.V., "A Fragment-Based Method to Discover Irreversible Covalent Inhibitors of Cysteine Proteases." Journal of Medicinal Chemistry, 2014, 57 (11), 4969-4974. "Highly Read Article of 2014"

An, H.; Krist, D.T.; Statsyuk, A.V.,"Crosstalk between Kinases and Nedd4 family Ubiquitin Ligases." Mol. BioSyst, 2014, 10,1643-1657. 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.; Statsyuk, 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, 2932-2935.

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-Us, 2012, 51 (42), 8327-8329.

Statsuk, A.V.; Shokat, K.M., Methods in Molecular Biology, 2012, 795, 179-190.

Statsuk, A.V.; Maly, D.J.; Seeliger, M.A.; Fabian, M.A.; Biggs, W.H. 3rd; Lockhart, D.J.; Zarrinkar, P.P.; Kuriyan, J.; Shokat, K.M., J. Am. Chem. Soc., 2008, 130, 17568-74.

Statsuk, A.V.; Bai, R.L.; Baryza, J.L.; Verma, V.A.; Hamel, E.; Wender, P.A.; Kozmin, S.A., Nature Chemical Biology, 2005, 7, 383-388.

Statsuk, A.V.; Liu, D.; Kozmin, S.A., J. Am. Chem. Soc. 2004, 31, 9546-9547.

Nenajdenko V.G.; Statsuk A.V.; Balenkova E.S., Chemistry of Heterocyclic Compounds, 2003, 5, 598-603.

Nenajdenko, V.G.; Statsuk, A.V.; Balenkova, E.S., Tetrahedron, 2000, 35, 6549-6556.

Abstracts and Presentations

Invited Conference Presentations

  • Discovery on Target, Targeting the Ubiquitin Proteasome System Cambridge Healthtech Institute, San Diego, CA. Title: "Technologies to discover E3 ligase inhibitors, activators, and degraders." Sept. 2018
  • Drug Discovery Chemistry Conference, Ubiquitin Proteasome System Cambridge Healthtech Institute, San Diego, CA. Title: "Technologies to discover E3 ligase inhibitors, activators, and degraders." April 2018
  • ACS Regional Meeting, Southwest, Lubbock, TX. Title: "HECT E3 and RBR E3 ligases as drug targets to treat cancer and neurodegenerative diseases: basic science and new screening technologies." Oct. 2017
  • 15th Annual Discovery on Target, 5th Annual Targeting the Ubiquitin Proteasome System Conference, Cambridge Healthtech Institute, Boston, MA. Title: "HECT E3 and RBR E3 ligases as drug targets to treat cancer and neurodegenerative diseases: basic science and new screening technologies." Sept. 2017
  • Drug Discovery Chemistry Conference, Protein-Protein Interactions 2 Cambridge Healthtech Institute, San Diego, CA. Title: "High Throughput Screening To Target HECT E3s Using UbFluor." April 2017
  • 14th Annual Discovery on Target, 4th Annual Targeting the Ubiquitin Proteasome System Conference, Cambridge Healthtech Institute, Boston, MA. Title: "High Throughput Screening To Target HECT E3s Using UbFluor." Sept. 2016.
  • Functional Disulfide Bonds in Health and Disease, FASEB, Steamboat Springs, CO. Title: "Covalent tethering a novel technology to target catalytic and non-catalytic cysteines." Aug. 2016.
  • Applied Pharmaceutical Chemistry 2016, Broad Institute, Boston, MA. Title: "Novel Technologies For HECT and RBR E3 Ubiquitin Ligases." April 2016.
  • Enzymes in Drug Discovery Summit 2016, 6th Ubiquitin Research & Drug Discovery Conference, GTCbio Conferences, San Diego, CA. Feb. 2016
  • 13th Annual Discovery on Target, 3rd Annual Targeting the Ubiquitin Proteasome System Conference, Cambridge Healthtech Institute, Boston, MA. Title: "Novel Fluorescent Probes UbFluor to Measure the Activity of E3 Ubiquitin Ligases." Sept. 2015
  • 12th Annual Mastering Medicinal Chemistry, Cambridge Healthtech Institute, Boston, MA. Title: "Discovery of Covalent Inhibitors of Nedd4-1 Ubiquitin Ligase: First-In-Class Covalent Inhibitor of HECT E3s." Marked by Cambridge Healthtech Institute as top four medicinal chemistry studies from Pfizer, BMS, Cubist and Northwestern. June 2015
  • Chemical Biology and Proteomics for Target Validation Cambridge Healthtech Institute, Boston, MA. Title: "Novel Probes for E3 Ligases: pH Cleavable Photocrosslinkers to Map E2/E3 Ligase PPI Interface and UbiFlu Novel Fluorescent Probes to Study E3 ligases." June 2015
  • 10th Annual Drug Discovery Chemistry, Fragment-Based Drug Discovery, From Hits to Leads and Lessons Learned, Cambridge Healthtech Institute, San Diego, CA. Title: "Irreversible Tethering: Fragment-Based Drug Discovery Technology for Covalent Enzyme and PPI Inhibitor Discovery." April 2015
  • 34th Midwest Enzyme Chemistry Conference (MECC), Northwestern University, Evanston, IL. Title: "Chemical Tools To Study E3 Ligases." Sept. 2014
  • 4th International Conference on Proteomics & Bioinformatics, Chicago, IL. Title: "The Ubiquitin System." Aug. 2014
  • 20th Anniversary of the Shokat Group, San Francisco, CA. Title: "The Ubiquitin System: Summary." July 2014
  • Natural Products Conference, Chicago, IL. Title: "The Ubiquitin System." July 2014
  • 37th Steenbock Symposium, The Future of Chemical Biology University of Wisconsin-Madison. Title: "The Ubiquitin System." June 2014
  • 246th ACS National Meeting & Exposition, Division of Biological Chemistry. Indianapolis, IN. Title: "Development of activity based probes for ubiquitin and ubiquitin-like protein signaling pathways." (Young Investigator Symposium). Sept. 2013
  • 5th Annual Ubiquitin Drug Discovery & Diagnostics Conference, Philadelphia, PA. Title: "Activity-Based Probes For Ubiquitin-Like Signaling Pathways." July 2013
  • 2013 Pew Annual Meeting, Veiques, Puerto Rico. Title: "Understanding Ubiquitin and Ubiquitin-Like Systems." July 2013
  • 4th Annual Chicago Organic Symposium, University of Illinois at Chicago, Title: "Chemistry of The Ubiquitin Proteasome System." July 2012

Invited Academic Presentations

  • CHM Grand Rounds, Oregon Health & Science University, Portland, OR. Oct. 2018
  • Invited lecture on the occasion of the opening of PhD program in Drug Discovery (Bonn International Graduate School of Drug Sciences), University of Bonn, Bonn, Germany. Dec. 2017
  • Emil J. Freireich Leukemia Hematology Grand Rounds, MD Anderson Cancer Center, Houston, TX. Oct. 2017
  • University of Texas Medical Branch at Galveston, Dept. of Pharmacology & Toxicology, Galveston, Tx. Oct. 2017
  • MJ Fox Foundation Parkin Consortium Meeting, New York, NY. May 2017
  • Department of Chemistry and Biochemistry, UC Santa Cruz, CA. March 2016
  • Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX. Feb. 2016
  • St. Jude Children’s Research Hospital, Dept. of Chemical Biology & Therapeutics, Memphis, TN, Oct. 2015
  • Feinberg School of Medicine, NU, Dept. of Biochemistry and Molecular Genetics, Chicago, IL, Sept. 2015
  • Medical College of Wisconsin, Dept. of Biochemistry, Milwaukee, WI, Sept. 2015
  • Northern Illinois University, Dept. of Biological Sciences, DeKalb, IL, Sept. 2015
  • Williams College, Dept. of Chemistry, Williamstown, MA, Sept. 2015
  • University of Pennsylvania, Dept. of Chemistry, Philadelphia, PA, Sept. 2015
  • University of Utah, Dept. of Chemistry, Salt Lake City, UT, Sept. 2015
  • Scripps Research Institute, La Jolla, CA, June 2015
  • University of California San Diego, Dept. of Chemistry and Biochemistry, La Jolla, CA, June 2015
  • University of Illinois at Urbana-Champaign, Dept. of Chemistry, Urbana, IL, May 2015
  • University of Kansas, Dept. of Chemistry, Lawrence, KS, May 2015
  • University of Chicago, Dept. of Chemistry, Chicago, IL, May 2015
  • Oregon Health & Science University, Dept. of Physiology and Pharmacology, Portland, OR, April 2015
  • University of Texas Medical Branch at Galveston, Dept. of Pharmacology & Toxicology, ;Galveston, TX, March 2015
  • Emory University, Dept. of Chemistry, Atlanta, GA, March 2015
  • Amherst College, Dept. of Chemistry, Amherst, MA, Feb. 2015
  • Boston College, Dept. of Chemistry, Boston, MA, Feb. 2015
  • University of Washington, Dept. of Chemistry, Seattle, WA Feb. 2015
  • University of Texas at Austin, Dept. of Chemistry, Austin, TX, Feb. 2015
  • Jackson State University, Dept. of Chemistry, Jackson, MI, Jan. 2015
  • University of California, Santa Barbara, Dept. of Chemistry, Santa Barbara, CA, Dec. 2014
  • University of South California, Dept. of Chemistry, Los Angeles, CA, Dec. 2014
  • Washington University, Dept. of Chemistry, St. Louis, MO, Nov. 2014
  • Purdue University, Dept. of Chemistry, West Lafayette, IN, Nov. 2014
  • Illinois Institute of Technology, Dept. of Chemistry, Chicago, IL, Sept. 2014
  • Icahn School of Medicine at Mount Sinai, Department of Structural and Chemical Biology, New York, NY, Jan. 2014
  • University of Illinois at Chicago, Dept. of Medicinal Chemistry and Pharmacognosy, Chicago, IL, Nov. 2012
  • Illinois Institute of Technology, Dept. of Chemistry, Chicago, IL, Sept. 2010

Invited Industry Presentations 

  • Genentech, San Francisco, CA “Biochemistry and Pharmacology of the Ubiquitin System July 2015
  • AstraZeneca, Boston, MA “Drugging Tumor Suppressor Proteins by Targeting the Ubiquitin System” Dec. 2014

Awards and Honors

  • 2012 Pew Scholar in the Biomedical Sciences

Editorial Appointments

Journal Reviewer

  • ACS Chemical Biology
  • Blood Journal
  • Chemistry – A European Journal
  • Chemistry and Biology
  • Journal of Molecular Biology
  • Nature Protocols
  • Organic Letters
  • PNAS
  • Scientific Reports
  • Science Signaling
  • Nature Communications

Service Activities

  • 2016 Scientific Advisory Board Member of the Chemical Probes Portal
  • 2015 Ad hoc reviewer, NIH Drug Discovery and Development SBIR/STTR proposals, NIH
  • Session Chair, Novel Synthetic Methods For Modulation Of Biological Processes, Chemical Biology and Proteomics for Target Validation, Cambridge Healthtech Institute, Boston, MA, 2015
  • Session Chair, Chemoproteomic Strategies For Inhibitor Development, Chemical Biology and Proteomics for Target Validation, Cambridge Healthtech Institute, Boston, MA, 2015
  • Moderator, Round Table Topics, Novel Approaches Targeting Protein-Protein Interactions Chemical Proteomics for Target Validation, Cambridge Healthtech Institute, Boston, MA, 2015
  • Moderator, Round Table Topics, Challenges and Opportunities for Ubiquitin System Drug Discovery, Chemical Proteomics for Target Validation, Cambridge Healthtech Institute, Boston, MA, 2015
  • Organizer and Co-Chair, H-Foundation Basic Science Symposium: Protein Degradation and Proteostasis from Fundamental Science to Cancer Therapies, 2015
  • Session Chair, 4th International Conference on Proteomics & Bioinformatics, Chicago, IL, 2015