Nucleophilic proteases: structure, function, regulation and disease
June 20–21, 2025
Virtual
There are more than 600 proteases in the human genome making it the second largest family of proteins in humans. These proteolytic enzymes are tightly regulated and function by performing post-translational protein modifications through hydrolysis of peptide bonds which results in activation or deactivation of biological pathways in an enormous array of physiological processes. Dysregulated proteolysis is also implicated in a large, diverse set of diseases including those relating to cardiovascular, immunological and cancer. Furthermore, the pathogenesis of many infectious diseases is mediated by proteases, either from the microbe, the host or both.
These enzymes are classified by their catalytic mechanism into five types: serine, threonine, cysteine, aspartic and metalloproteases. This year we expand upon past meetings by highlighting the most significant recent studies not only on serine, but also on the other classes of nucleophilic threonine and cysteine proteases. The talks organized present aspects of protease biochemistry and biophysics such as structural biology, as well as drug discovery and inhibitor development. Cross-disciplinary topics include cancer, infectious disease (viruses, bacteria, other pathogens), inflammation and immunology, cardiovascular system, and others.
Organizers
Philipps University of Marburg
Washington University in St. Louis
Torsten Steinmetzer
Philipps University of Marburg
Sponsors
Program schedule
All times are U.S. Eastern.
Friday June 20
Saturday June 21
Friday agenda
Session 1
Moderator: Anthony O’Donoghue
Membrane anchored serine proteases in ovarian cancer metastasis
Toni Antalis, University of Maryland
Discovering novel SARS-CoV-2 inhibitors targeting the main protease Mpro: from virtual screening to hit optimization
Laura Goracci, University of Perugia
Identification of a potent pan-coronaviral inhibitor
Joanne Lemieux, University of Alberta
Tuning selectivity of activity-based probes for cysteine proteases
Steven Verhelst, KU Leuven
Role of preeclampsia-associated serine protease prostasin in embryonic hematopoiesis and vessel remodeling
Sara Di Carlo, University of Lausanne
Break
Session 2
Moderator: Joanne Lemieux
New tools to facilitate drug discovery for pathogen proteasomes
Anthony O鈥橠onoghue, University of California, San Diego
From peptidic to new non-peptidic inhibitors of the proprotein convertase furin as potential broad-spectrum antiviral agents
Torsten Steinmetzer, Philipps University Marburg
Mechanistic understanding of proprotein convertase activation guides the development of highly specific furin inhibitors
Sven Dahms, University of Salzburg
Allosteric inhibition mechanisms of β-tryptase tetramers and monomers by antibodies: implications for mast cell diseases
Bob Lazarus, Genentech
Crystallographic investigations into the acyl-enzyme step of serine and cysteine proteases
Mark Paetzel, Simon Fraser University
Break
Flash talks
Moderator: James Janetka
Mechanism of assembly-coupled autocatalytic activation of the proteasome
John Hannah, Harvard Medical School
Protease substrate profiling using molecular indexing of proteins by self-assembly
Wayne D. Monteiro, Johns Hopkins University
Proteolytic activation of influenza HA begins intracellularly and is most efficient in multi-ciliated cells
Zijian Guo, Washington University in St. Louis
Novel activators of the mitochondrial protease ClpP and their application to disease
Lee M. Graves, University of North Carolina at Chapel Hill
Development of small molecule inhibitors and PROTACs against Chikungunya virus protease nsP2
Muhammad A. Rahat, University of Massachusetts Amherst
Positional scanning and structural modeling uncover key determinants of human legumain transpeptidase substrate specificity
Elfriede Dall, University of Salzburg
Poster session
- Mechanism of assembly-coupled autocatalytic activation of the proteasome
John Hannah, Harvard Medical School - Protease substrate profiling using molecular indexing of proteins by self-assembly
Wayne D. Monteiro, Johns Hopkins University - Proteolytic activation of influenza HA begins intracellularly and is most efficient in multi-ciliated cells
Zijian Guo, Washington University in St. Louis - Novel activators of the mitochondrial protease ClpP and their application to disease
Lee M. Graves, University of North Carolina at Chapel Hill - Development of small molecule inhibitors and PROTACs against Chikungunya virus protease nsP2
Muhammad A. Rahat, University of Massachusetts Amherst - Positional scanning and structural modeling uncover key determinants of human legumain transpeptidase substrate specificity
Elfriede Dall, University of Salzburg - Cutting through complexity: Structural insights into ADAMI 7 regulation by iRhoms
Tom Seegar, University of Cincinnati - K48-ubiquitin-activated proteases cut-up post-ER proteins
Annabel Minard, University of Iowa
Saturday agenda
Session 1
Moderator: Eva Friebertshaeuser
Dual functional role of a kallikrein 3 genetic variant: implications for prostate cancer progression and biomarker interpretation
Jyotsna Batra, Queensland University of Technology
Quest for inhibition of cell entry of SARS-CoV-2 and other viruses — All roads lead to cathepsins
Dusan Turk, Jo啪ef Stefan Institute
Targeting coronavirus major protease with broad spectrum activity and favorable bioavailability
Charles Craik, University of California, San Francisco
Druglike, radiotheranostic ligands of fibroblast activation protein (FAP) with optimized residence times: from design to preclinical evaluation in oncology models
Pieter Van der Veken, University of Antwerp
The canonical and noncanonical roles of the proprotein convertases in health and disease: emphasis on cardiovascular diseases and cancer/metastasis
Nabil Seidah, IRCM, University of Montreal
Break
Session 2
Moderator: Dusan Turk
Role of proteases in protein quality control and aging
Fabio Demontis, St. Jude Children's Research Hospital
Biochemical and structural tools to interrogate trypsin-like serine protease zymogen activation
Bryan Fraser, University of Toronto
Selective inhibitors for studying the enigmatic neutrophil serine protease 4
Daniel Kirchhofer, Genentech
Harnessing protease activity of the tumor microenvironment with RIPs as a novel modality to deliver targeted radiotherapeutics
Grant Blouse, TheraPaint Inc.
Break
Flash talks
Moderator: Torsten Steinmetzer
Macrocyclic phage display for identification of selective protease substrates
Marta Barniol鈥揦icota, Universitat Pompeu Fabra
A novel nanobody-drug conjugate targeting the host cell protease furin for antiviral therapy
Konstantin Bloch, Philipps University Marburg
Structural basis for chaperone-mediated activation of proprotein convertases in the secretory system
Daniel Kober, University of Texas Southwestern Medical Center
Targeting autocrine HGF maturation via novel HGF protease inhibitors overcomes cetuximab resistance in colorectal cancer
Bhuminder Singh, Vanderbilt University Medical Center
Poster session
- Macrocyclic phage display for identification of selective protease substrates
Marta Barniol–Xicota, Universitat Pompeu Fabra - A novel nanobody–drug conjugate targeting the host cell protease furin for antiviral therapy
Konstantin Bloch, Philipps University Marburg - Structural basis for chaperone-mediated activation of proprotein convertases in the secretory system
Daniel Kober, University of Texas Southwestern Medical Center - Targeting autocrine HGF maturation via novel HGF protease inhibitors overcomes cetuximab resistance in colorectal cancer
Bhuminder Singh, Vanderbilt University Medical Center - Natural protein cathepsin inhibitor: Subcellular localization and potential anti-SARS-CoV-2 activity
Nata拧a Lindic, Jo啪ef Stefan Institute - Upregulation of cysteine cathepsin L and legumain upon interaction of neurons with the SARS-CoV-2 spike protein
Klaudia Brix, Constructor University Bremen - Quercetin attenuates oxidative stress in sodium nitroprusside-induced hepatic injury in rats
Nathan Rimamsanati, Federal University Wukari - Tanespimycin (17 AAG), an HSP90 inhibitor, exhibits superior inhibition of SARS-CoV-2 main protease (Mpro) compared to the clinically approved drug Nirmatrelvir
Gargi Mukherjee, Shiv Nadar University - Involvement of MMP-9 in doxorubicininduced B-Raf degradation in human cancer cells: A new trick for an old dog?
Pramod Mahajan, Drake University