Oct. 28–30, 2021 | Virtual

Serine Proteases

in Pericellular Proteolysis and Signaling

Serine proteases in pericellular proteolysis and signaling
Oct. 28–30, 2021 | Virtual | Paid registration required

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

The conference traditionally brings together the leading national and international researchers in the field of pericellular proteolysis and provide them with a forum to present their latest findings, exchange ideas and technologies, and network to form collaborations. Equally important, it also provides a venue for junior investigators at the graduate student and postdoctoral level to discuss their current research, meet with experts in the field and forge new scientific interactions crucial for their future career development. To this end, we plan an interactive poster session and easy access to poster presenters' video recordings to increase the visibility of their work. Holding the meeting virtually provides a unique opportunity to make this conference even more accessible to students as well as to investigators from other fields where pericellular proteolysis is implicated.

Topics covered

Cleavage of proteins in the extracellular environment, including hormones, growth factors and their receptors, ion channels, cell adhesion molecules and structural components of extracellular matrix, plays a key role in the regulation of cell behavior. Among more than 500 proteolytic enzymes encoded by mammalian genomes, membrane-anchored serine proteases, which are expressed on the cell surface in all major organs, are excellently suited to mediate signal transduction across the plasma membrane and are increasingly being recognized as important regulators of organ development and homeostasis. At the same time, unrestrained pericellular proteolysis has been shown to contribute to epithelial and endothelial barrier dysfunction, inflammatory, cardiovascular, and respiratory diseases, as well as cancer. Many of the influenza- and coronavirus-type viruses, including SARS-CoV-2, are now known to also use activity of these proteases to gain entry into the target cell, making MASPs a major determinant of cell susceptibility to infection.

In addition to the roles of serine proteases in viral biology, the meeting will cover topics including biosynthesis, trafficking and post-translational modifications, endogenous and pharmacological inhibitors, developmental and other physiological functions, mechanisms of dysregulation and pathological consequences, and molecular mechanisms of protease-mediated signaling.

Important dates

Oct. 27 Registration deadline

Organizers

Daniel Kirchhofer
Daniel Kirchhofer
Genentech Inc.
Suzanne Jackowski
Roman Szabo
National Institute of Dental and Craniofacial Research, NIH

Sponsors

Program schedule

All times listed are U.S. Eastern Daylight Time (GMT-4)

Thursday October 28
Friday October 29
Saturday October 30

Thursday agenda

10:00 AM - 12:15 PM

Session 1: Proteases in viral biology

Session chairs:

  • Klaudia Brix, Jacobs University
  • James Harte, University College Cork
Proteolytic activation of SARS-CoV-2 and its inhibition
Stefan Poehlmann, German Primate Center
Type II transmembrane serine proteases inhibitors prevent SARS-CoV-2 infection
Sébastien Dion, Université de Sherbrooke
TMPRSS2 is the major activating protease of influenza A virus of different HA-subtype in murine and human airways and influenza B virus in human lung 
Hannah Limburg, Marburg University
Implications of Spike-glycoprotein processing at S1/S2 by Furin, at S2’ by Furin and/or TMPRSS2 and shedding of ACE2: Cell-to-cell fusion, cell entry and infectivity of SARS-CoV-2
Nabil Seidah, Clinical Research Institute of Montreal
12:35 PM - 2:15 PM

Session 2: Development and physiology

Session chairs:
  • Celine Deraison, Digestive Health Research Institute
  • Joy Armistead, University of Cologne
What is new about the proteolytic activation of ENaC by proteases in the kidney?
Edith Hummler-Beermann, University of Lausanne
Protease function in uterine spiral artery remodeling
Qingyu Wu, Soochow University
Zymogen-locked mutant prostasin (Prss8) leads to incomplete proteolytic activation of the epithelial sodium channel (ENaC) and severely compromises triamterene tolerance in mice
Ferruh Artunc, University Hospital Tuebingen
Par2 is one of several targets for deregulated matriptase activity in Hai-1-deficient embryos and mice
Eric Camerer, Inserm
2:35 PM - 4:00 PM

Session 3: Inflammation and immunity

Session chairs:
  • Karin List, Wayne State University School of Medicine
  • Fabienne Birkle, University of Michigan
Plasminogen Deficiency Leads to Periodontitis Susceptibility
Lakmali Silva, National Institutes of Health
The couple ELA2/ELAFIN in the vicinity of epithelial cells participates to the intestinal mucosal integrity
Celine Deraison, Digestive Health Research Institute
3:15 PM - 4:00 PM

Flash talks

Characterizing the post-translational modifications of the pro-oncogenic protease TMPRSS13
Carly Martin, Wayne State University

New perspectives of aging: TMPRSS11a as a new target
Christian Fernandez, Universidad de Chile

Engineering serpin-based inhibitors for the specific and selective inhibition of furin and other proprotein convertases
Gonzalo Izaguirre, University of Illinois

Design and characterization of fluorescent activity-based probes for imaging fibroblast activation protein (FAP) activity in the tumor microenvironment
Yentl Van Rymenant, University of Antwerp

Improving protease cleavage site prediction with AlphaFold database 3D structural data
Evgenii Matveev, Skolkovo Institute of Science and Technology

Development of a custom protease design pipeline, incorporating high-throughput experimentation, computational structure prediction and machine learning
Joseph Lubin, Rutgers University–New Brunswick

Contribution of pericellular cysteine cathepsins to priming of the SARS-CoV-2 spike protein at cilia of thyroid epithelial cells
Klaudia Brix, Jacobs University

The structure of SARS-CoV-2 spike glycoprotein complex with human fruin and TMPRSS2 and its genetic variants, insights the mechanism of viral activation and entry
Naveen Vankadari, Monash University

Enoxaparin augments alpha-1-antitrypsin inhibition of TMPRSS2 activity: a promising drug combination against COVID-19
Ashley Buckle, Monash University

Friday agenda

9:55 AM - 12:00 PM

Session 4: Biosynthesis, structure and cellular regulation

Session chairs:
  • Qingyu Wu, Soochaw University 
  • Frida Berlin, Lund University
Hepatocyte growth factor activator inhibitor-1 (HAI-1)/SPINT1 of cancer cells: Friend or foe in invasive growth?
Hiroaki Kataoka, University of Miyazaki
Activation, inhibition and deregulation of the matriptase pathway
Lotte Vogel, University of Copenhagen
The ectodomain of matriptase-2 plays an important non-proteolytic role in suppressing hepcidin expression in mice
An-Sheng Zhang, Oregon Health Sciences University
11:20 AM - 12:00 PM

Flash talks

The protease corin regulates glucose, lipid and energy metabolism in mice
Xianrui Zhang, Soochow University

Interaction of Dengue virus non-structural protein 3 protease domain with its co-factor, NS2b, and mechanism of substrate specificity
Armul Simanchal Dora, National Institute of Science Education and Research

Chymotrypsin in the gut: more than just a food digestion enzyme
Simon Guignard, Inserm

ST14 mutations causing ichthyosis-hypotrichosis syndrome causes the production of matriptase devoid of the ability to activate prostasin
Lasse Holt-Danborg, University of Copenhagen

The membrane anchored serine protease (MASP) matriptase in ovarian cancer dissemination and metastasis
Nisha Pawar, University of Maryland, Baltimore

A sphingolipid rheostat downstream of matriptase-1 / ST14 controls apoptosis and apical cell extrusion in zebrafish hai1a mutant epithelium
Joy Armistead, University of Cologne

A serpin from tick saliva inhibits kallikrein-initiated intrinsic pathway of blood coagulation
Jan Kotál, National Institutes of Health

Human and mouse kallikrein-related peptidases 7 (KLK7) undergo autolysis, providing a potential additional layer of negative proteolytic regulation
Swapnil Ghodge, Genentech Inc.

12:20 PM - 2:50 PM

Session 5: Cancer development and progression

Session chairs:

  • Grant Blouse, Catalyst Biosciences
  • Nisha Pawar, University of Maryland, Baltimore
Global protease activity profiling identifies HER2-driven proteolysis in breast cancer
Charles Craik, University of California, San Francisco
Membrane serine proteases in hemostasis and cancer
Toni Antalis, University of Maryland School of Medicine
Cell-surface serine proteases as tumor promoters or tumor suppressors
Karin List, Wayne State University School of Medicine
Stage-dependent functions of dipeptidyl peptidase 9 in mammary cancer progression
Lisa Hess, University of Freiburg
Novel activities of the GPI-anchored serine protease testisin in the regulation of coagulation and fibrinolysis
Marguerite Buzza, University of Maryland
Matriptase activation via hypotonic stress and polarity defects induces epidermal tumors through PI3K-Akt-mTORC1-NFkB in zebrafish
Julia Hatzold, University of Cologne
3:00 PM - 4:00 PM

Poster discussion session

Saturday agenda

9:55 AM - 12:00 PM

Session 6: Development of tools for imaging and diagnosis

Session chairs:

  • Toni Antalis, University of Maryland School of Medicine
  • Lasse Holt-Danborg, University of Copenhagen
Imaging of protease activity using recombinant Probody therapeutics
Olga Vasilieva, CytomX Therapeutics Inc.
Uncovering the dynamics of proteolytic activity in human milk
Anthony O'Donoghue, University of California, San Diego
Design of selective active-based probes for imaging of proteases in coagulation pathway
Marcin Drag, Wroclaw University of Science and Technology
In vivo measurement of granzyme proteolysis from activated immune cells with PET
Conner Bardine, University of California, San Francisco
Kallikrein 5 inhibition by the lympho-epithelial kazal-type related inhibitor hinders matriptase-dependent carcinogenesis
Katiuchia Sales, Ribeirao Preto Medical School
12:20 PM - 2:50 PM

Session 7: Targeting protease activity in human disease

Session chairs:

  • Lucas Tirloni, National Institute of Allergy and Infectious Diseases
  • Carly Martin, Wayne State University
Inhibition of β-tryptase for severe asthma by antibodies with distinct allosteric mechanisms of action
Bob Lazarus, Genentech Inc.
Covalent TMPRSS2 and matriptase inhibitors as antiviral and anticancer agents
James Janetka, Washington University School of Medicine
Engineering complement factor I as a protease medicine: Tuning potency and specificity for complement-mediated disorders
Grant Blouse, Catalyst Biosciences
Allosteric inhibition of HtrA1 activity by a conformational "lock" mechanism to treat age-related macular degeneration
Stefan Gerhardy, Genentech Inc.
Generation and characterisation of KY1066, a fully human antibody targeting the enzymatic activity of matriptase-2 for the treatment of iron overload in β-thalassemia
Anais Palin, Inserm
Hepsin regulates TGFβ signaling via fibronectin proteolysis
Denis Belitskin, University of Helsinki
3:15 PM - 3:45 PM

Business meeting/Awards ceremony

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