Serine Proteases in Pericellular Proteolysis and Signaling

September 12–15, 2019
Potomac, Md.


Eric Camerer, INSERM
Bob Lazarus, Genentech, Inc.

The 2019 symposium on Serine Proteases in Pericellular Proteolysis and Signaling continues the tradition of the special symposia on membrane-anchored serine proteases with an expanded focus on other serine proteases with overlapping substrates and functions in the pericellular environment.

Proteases account for approximately 2% of mammalian proteome. A subset of these in the serine protease superfamily are actively involved in coordinating organ development and cellular behavior through proteolytic processing of hormones, growth factors, membrane receptors and ion channels. While some, such as the membrane-anchored serine proteases (MASPs), contain transmembrane domains or lipid anchors, others make use of plasma membrane cofactors and other mechanisms to direct their activities to the pericellular environment. Pericellular proteolysis is important for organ development and homeostasis but can also contribute to epithelial and endothelial barrier dysfunction, inflammatory disease, cancer, cardiovascular disease and neurodegenerative diseases if protease activities are not adequately restrained. Understanding the biochemistry and biology of these proteases and their regulators is therefore of great interest to basic science, clinical research and drug development.

Program schedule

Thursday September 12
Friday September 13
Saturday September 14
Sunday September 15

Thursday agenda

7:40 PM - 8:40 PM

Keynote lecture

Engineered proteases for cell signaling and bioconjugation
Jim Wells, University of California, San Francisco

Friday agenda

9:00 AM - 12:10 PM

Session 1: Development and Physiology

Discussion leaders: Karin List and Leonard Drees

Membrane-anchored serine proteases as regulators of epithelial function
Roman Szabo, National Institutes of Health
Tissue ecology: Sensing and responding to local differences in cellular fitness
Laura A. Johnston, Columbia University Medical Center
Proteolytic processing of TGF-beta type III receptors by matriptase as a novel mechanism in development and disease
Leonard Drees, Max Planck Institute for Biophysical Chemistry
Matriptase-2, an essential regulator of iron homeostasis
Delphine Meynard, INSERM
HAI-2/SPINT2 maintains epithelial architecture in digestive tracts
Hiroaki Kataoka, University of Miyazaki
Hepsin promotes liver glucose and lipid metabolism via HGF/c-Met signaling
Shuo Li, Cleveland Clinic Lerner Research Institute
Expression and function of the protease corin in the eccrine sweat glands
Mailing He, Soochow University
3:00 PM - 6:30 PM

Session 2: Molecular tools for imaging, diagnosis and targeting in health and disease

Discussion leaders: Daniel Kirchhofer and Swapnil Ghodge 

In search of optimal technology for simultaneous imaging of proteases
Marcin Drag, Wroclaw University of Science and Technology
HtrA1 biomarker discovery using proteomics
Victoria Pham, Genentech, Inc.
Covalent inhibition of herpesvirus protease by tethering to a conserved non-catalytic cysteine
Kaitlin Hulce, University of California, San Francisco
Linking caspase cleavage of latent sequences in the proteome to protein homeostasis
Charles S. Craik, University of California, San Francisco
Peptidomimetic inhibitors of HGF-activation proteases in lung cancer
James Janetka, Washington University School of Medicine in St. Louis
Point-of-care quantitation of protease activity in biofluids
Anthony O’Donoghue, University of California, San Diego

Saturday agenda

9:00 AM - 12:00 PM

Session 3: Biosynthesis, trafficking, structure and cellular regulation

Discussion leaders: Ningzheng Dong and Kaitlin Hulce

Regions of conformational flexibility in the serine protease PCSK9 and design of antagonists for lipid lowering
Daniel Kirchhofer, Genentech, Inc.
Identification of novel TMPRSS6 isoforms interacting partners: towards a better understanding of the protease function
Sébastien Dion, Université de Sherbrooke
KLK14 mediated MT-MMP processing as an alternative pathway of surface MMP activation
Tomasz Kantyka, University of Bergen
Cellular mechanisms of the membrane topology of corin
Qingyu Wu, Cleveland Clinic Lerner Research Institute
Regulation of corin expression by Krüppel-like factor 17 in the pregnant uterus
Zhiting Wang, Soochow University
Intramembrane proteolysis of epithin/PRSS14 promotes metastatic conversion
Chungho Kim, Korea University
The role of plasminogen activator inhibitor type-2 (PAI-2) in modulating venous thrombus resolution
Tierra Johnson, University of Maryland
2:30 PM - 5:30 PM

Session 4: Cancer

Discussion leaders: Toni Antalis and Topi Tervonen

Type II transmembrane serine proteases in cancer progression
Karin List, Wayne State University School of Medicine
Kallikreins and signaling in the tumor microenvironment
Judith Clements, Queensland University of Technology
Matriptase mediates lipopolysaccharide-induced prostate cancer cell invasion and metastasis
Ming-Shyue Lee, National Taiwan University
TMPRSS11B enhances lactate export and glycolytic metabolism in lung cancer
Kathryn A. O’Donnell, University of Texas Southwestern Medical Center
Ras signaling fuels early tumor invasion via hepsin
Juha Klefström, University of Helsinki
Anticancer approaches with peptide epitopes derived from and with monoclonal antibodies against autocatalytic loop of Prss14/epithin
Moon Kim, Inha University
Prostasin — a new player in tumor immune evasion
Li-Mei Chen, University of Central Florida College of Medicine

Sunday agenda

9:00 AM - 12:00 PM

Session 5: Inflammation, host defense and infection

Discussion leaders: Thomas Bugge and Nisha Pawar  

Activated protein C / protease-activated receptor-1 signaling and endothelial cytoprotection
JoAnn Trejo, University of California, San Diego
Regulation of microvascular permeability by the GPI-anchored serine protease testisin
Marguerite Buzza, University of Maryland
Role of protease-activated receptors in viral infections
Silvio Antoniak, University of North Carolina at Chapel Hill
Human mast cell αβ-Tryptases: Bench ↔ Bedside
Lawrence Schwartz, Virginia Commonwealth University
Molecular evolution and design of pegylated CB 2782 as a complement factor C3-inactivating protease for dry AMD
Grant Blouse, Catalyst Biosciences
Functional role of SPINK7 and kallikrein 5 in eosinophilic esophagitis
Nurit Azouz, Cincinnati Children's Hospital Medical Center
ELA2, an uncontrolled active elastase released by intestinal epithelial cells, participates to mucosal inflammation in IBD
Celine Deraison, INSERM