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Proteolytic Enzymes & Their Inhibitors
Gordon Research Conference

Exploring and Exploiting Proteases in Development and Disease

Dates

June 26 - July 1, 2016

Location

Renaissance Tuscany Il Ciocco
Lucca (Barga), Italy

Organizers

Chair:
Johanna A. Joyce

Vice Chair:
Matthew S. Bogyo

Meeting Description

Proteolysis is essential for numerous developmental and physiological processes. However, dysregulation of protease activity underlies many diseases and pathological conditions, including cancer, inflammation and infection. Given the importance of proteolysis, and the sheer scope of distinct protease functions, these enzymes essentially have an impact on every facet of biology, often through surprising and unexpected mechanisms.

In this meeting we will highlight innovative and cutting-edge research exploring the full spectrum of protease biology, in processes as diverse as ER stress, ubiquitination, growth factor signaling, cell death, organ patterning and stem cell niche regulation. We will emphasize the tremendous potential we now have as a community to exploit this knowledge through different therapeutic applications. This includes presenting the latest technologies for protease detection in various disease states, which can serve as diagnostic and/or prognostic read-outs. In addition, we will discuss new therapeutic approaches for targeting proteases in disease states including cancer, infection, fibrosis and inflammation.

Related Meeting

This GRC was held in conjunction with the "Proteolytic Enzymes & Their Inhibitors" Gordon Research Seminar (GRS). Refer to the associated GRS program page for more information.

Contributors

Final Meeting Program

Sunday
4:00 pm - 8:00 pmArrival and Check-in
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pmStem Cells and Development
Discussion Leaders: Margarete M.S. Heck (University of Edinburgh, United Kingdom) and Carl Blobel (Hospital for Special Surgery, Weill Cornell Medicine, USA)
7:40 pm - 8:05 pmJames Whisstock (Monash University, Australia)
"Proteolytic Regulation of Growth Factors in Developmental Biology"
8:05 pm - 8:15 pmDiscussion
8:15 pm - 8:30 pmSelected from Poster Abstracts: Antonino Schepis (University of California, San Francisco, USA)
"Matriptase/Par2 Signaling Regulates Cell Extrusion and Proliferation During Zebrafish Skin Development"
8:30 pm - 8:35 pmDiscussion
8:35 pm - 8:50 pmSelected from Poster Abstracts: Christoph Becker-Pauly (University of Kiel, Germany)
"A Unique Molecular Switch Regulates Shedding of Meprin β by ADAM Proteases in the Small Intestine Important for Mucus Barrier Function"
8:50 pm - 8:55 pmDiscussion
8:55 pm - 9:20 pmRama Khokha (University of Toronto, Canada)
"Uncovering New Biology Through TIMPless Models"
9:20 pm - 9:30 pmDiscussion
Monday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmAdvances in Analyzing Protease Activity and Function
Discussion Leaders: Irit Sagi (Weizmann Institute of Science, Israel) and Christopher Overall (The University of British Columbia, Canada)
9:00 am - 9:25 amMatthew Bogyo (Stanford University School of Medicine, USA)
"Small Molecule Probes of Protease Activity: Applications to Imaging and Drug Discovery"
9:25 am - 9:35 amDiscussion
9:35 am - 10:00 amUlrich Auf Dem Keller (ETH Zurich, Switzerland)
"Next-Generation Positional Proteomics"
10:00 am - 10:10 amDiscussion
10:10 am - 10:30 amSelected from Poster Abstracts: Burckhard Seelig (University of Minnesota, USA)
"Developing Comprehensive Specificity Profiling of Promiscuous Proteases"
10:30 am - 10:35 amDiscussion
10:35 am - 11:05 amCoffee Break
11:05 am - 11:30 amMarcin Drag (Wroclaw University of Technology, Poland)
"Unnatural Amino Acids as a Tool in Design of Specific Substrates and Activity Based Probes for Proteases"
11:30 am - 11:40 amDiscussion
11:40 am - 12:00 pmSelected from Poster Abstracts: Marko Fonovic (Jozef Stefan Institute, Slovenia)
"Fast Protease Specificity Profiling of Cysteine Cathepsins"
12:00 pm - 12:05 pmDiscussion
12:05 pm - 12:25 pmSelected from Poster Abstracts: Anthony O'Donoghue (University of California, San Diego, USA)
"Distinguishing the Human Immuno- and Constitutive Proteasomes with Global Substrate Specificity Profiling"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmProteases in Neural Development and Neurodegeneration
Discussion Leaders: Klaudia Brix (Jacobs University Bremen, Germany) and Hans-Ulrich Demuth (Fraunhofer IZI, Germany)
6:00 pm - 6:25 pmMichael Ehrmann (Universitaet Duisburg-Essen, Germany)
"Amyloid Fibril Degradation by Human PDZ Protease HTRA1"
6:25 pm - 6:35 pmDiscussion
6:35 pm - 6:55 pmJose Manuel Morante-Redolat (University of Valencia / CIBERNED, Spain)
"Proteolytic Regulation of Neural Stem Cell Behaviour"
6:55 pm - 7:05 pmDiscussion
7:05 pm - 7:20 pmSelected from Poster Abstracts: Joanne Lemieux (University of Alberta, Canada)
"Rhomboid-Mediated Intramembrane Proteolysis in Parkinson's Disease"
7:20 pm - 7:25 pmDiscussion
7:25 pm - 7:50 pmBart De Strooper (VIB, KU Leuven, Belgium)
"Proteolytic Processing in and Around the Cell Membrane in Alzheimer's Disease"
7:50 pm - 8:00 pmDiscussion
8:00 pmDinner
Tuesday
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmCell Signaling
Discussion Leaders: James McKerrow (University of California, San Diego, USA) and Jan Potempa (Jagiellonian University, Poland)
9:00 am - 9:25 amChristopher Overall (The University of British Columbia, Canada)
"A New MALT1 LUBAC Substrate Discovered by TAILS Puts the Brake on NFkB"
9:25 am - 9:35 amDiscussion
9:35 am - 10:00 amCarl Blobel (Hospital for Special Surgery, Weill Cornell Medicine, USA)
"iRhoms: Key Regulators of ADAM17-Dependent EGFR Signaling"
10:00 am - 10:10 amDiscussion
10:10 am - 10:25 amSelected from Poster Abstracts: Christopher LaRock (UC San Diego School of Medicine, USA)
"IL-1β Is an Innate Immune Sensor of Microbial Proteolysis"
10:25 am - 10:30 amDiscussion
10:30 am - 11:00 amCoffee Break
11:00 am - 11:25 amLaura Edgington-Mitchell (Monash Institute of Pharmaceutical Sciences, Monash University, Australia)
"Proteases on the Pathway to Pain: New Signaling Platforms for PAR2-Activating Proteases"
11:25 am - 11:35 amDiscussion
11:35 am - 11:50 amSelected from Poster Abstracts: Ruth Geiss-Friedlander (University Medical Center Goettingen (UMG), Germany)
"DPP9 Is a Novel Component of the N-End Rule Pathway Targeting the Tyrosine Kinase Syk"
11:50 am - 11:55 amDiscussion
11:55 am - 12:20 pmMatthew Freeman (University of Oxford, United Kingdom)
"Rhomboids, Signalling and Cell Biology"
12:20 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmTherapeutic Targeting of Proteases
Discussion Leaders: Galia Blum (Hebrew University of Jerusalem, Israel) and Christopher Scott (Queens University Belfast, United Kingdom)
6:00 pm - 6:25 pmIrit Sagi (Weizmann Institute of Science, Israel)
"Induction of Embryo Implantation by Collagenase I ECM Remodeling"
6:25 pm - 6:30 pmDiscussion
6:30 pm - 6:45 pmSelected from Poster Abstracts: Junichiro Sonoda (Genentech, Inc., USA)
"Endopeptidase FAP Cleaves and Inactivates FGF21"
6:45 pm - 6:50 pmDiscussion
6:50 pm - 7:05 pmSelected from Poster Abstracts: Gregg Fields (Florida Atlantic University, USA)
"Structure-Guided Design and Synthesis of Highly Selective Matrix Metalloproteinase 13 Inhibitors for the Treatment of Osteoarthritis"
7:05 pm - 7:10 pmDiscussion
7:10 pm - 7:20 pmSelected from Poster Abstracts: Edgar Deu (The Francis Crick Institute, United Kingdom)
"Dipeptidyl Aminopeptidase 3, a Malarial Cysteine Protease Playing a Major Role During RBC Invasion"
7:20 pm - 7:25 pmDiscussion
7:25 pm - 7:50 pmVicki Plaks (University of California, San Francisco, USA)
"Targeting the Extracellular Matrix for Anti-Metastatic Breast Cancer Therapy"
7:50 pm - 8:00 pmDiscussion
8:00 pmDinner
Wednesday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmCancer
Discussion Leaders: Christoph Peters (University of Freiburg, Germany) and Rama Khokha (University of Toronto, Canada)
9:00 am - 9:25 amMatthew Albert (Genentech, USA)
"Post-Translational Modification of Chemokines by DPP4 and Implications for Cancer Immunotherapy"
9:25 am - 9:35 amDiscussion
9:35 am - 10:00 amKlaudia Brix (Jacobs University Bremen, Germany)
"Nuclear Cysteine Cathepsins in Colorectal and Thyroid Carcinoma"
10:00 am - 10:10 amDiscussion
10:10 am - 10:25 amSelected from Poster Abstracts: Shishir Pant (University of Helsinki, Finland)
"Oncogenic Role of Serine Protease Hepsin in Breast Cancer"
10:25 am - 10:30 amDiscussion
10:30 am - 11:00 amCoffee Break
11:00 am - 11:25 amOliver Schilling (University of Freiburg, Germany)
"Proteolytic Processing in the Progression of Low-Grade Astrocytomas to Glioblastoma Multiforme"
11:25 am - 11:35 amDiscussion
11:35 am - 11:50 amSelected from Poster Abstracts: Leila Akkari (University of Lausanne, Switzerland)
"Combined Deletion of Cathepsin Protease Family Members Reveals Compensatory Mechanisms in Cancer"
11:50 am - 11:55 amDiscussion
11:55 am - 12:20 pmThomas Reinheckel (Medical Faculty, University of Freiburg, Germany)
"The Proteolytic Landscape of Tumor-Initiating Breast Cancer Cells"
12:20 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmStructural Insights into Cell Biology of Proteases
Discussion Leaders: Sheena McGowan (Monash University, Australia) and James Huntington (University of Cambridge, United Kingdom)
6:00 pm - 6:25 pmTania Baker (Massachusetts Institute of Technology, USA)
"Subunit Paralogs that Alter the Specificity, Activity and Inhibitor Resistance of AAA+ Proteases"
6:25 pm - 6:35 pmDiscussion
6:35 pm - 7:00 pmTim Clausen (Research Institute of Molecular Pathology (IMP), Austria)
"Revealing a Phospho-Signal that Serves as a Specific Degradation Tag"
7:00 pm - 7:10 pmDiscussion
7:10 pm - 7:20 pmEdward Morris (Institute of Cancer Research, United Kingdom)
"Structure of the Hybrid Proteasome"
7:20 pm - 7:25 pmDiscussion
7:25 pm - 7:50 pmSinisa Urban (Johns Hopkins University School of Medicine, USA)
"From Atomic to Cellular Resolution of Rhomboid Proteolysis Inside the Membrane"
7:50 pm - 8:00 pmDiscussion
8:00 pmDinner
Thursday
7:30 am - 8:30 amBreakfast
8:30 am - 9:00 amBusiness Meeting
Nominations for the Next Vice Chair; Fill in Conference Evaluation Forms; Discuss Future Site and Scheduling Preferences; Election of the Next Vice Chair
9:00 am - 12:30 pmNew Strategies for Protease Inhibition
Discussion Leaders: Matthew Bogyo (Stanford University School of Medicine, USA) and Thomas Reinheckel (Medical Faculty, University of Freiburg, Germany)
9:00 am - 9:25 amPaula Da Fonseca (MRC Laboratory of Molecular Biology, United Kingdom)
"High Resolution Cryo-EM in the Development of New Specific Proteasome Inhibitor"
9:25 am - 9:35 amDiscussion
9:35 am - 10:00 amHenry Maun (Genentech, Inc., USA)
"Mechanisms of Allosteric Activation and Inhibition of Tryptase"
10:00 am - 10:10 amDiscussion
10:10 am - 10:30 amSelected from Poster Abstracts: Stephanie Polderdijk (Cambridge University, United Kingdom)
"An Engineered Serpin for the Treatment of Haemophilia"
10:30 am - 10:35 amDiscussion
10:35 am - 11:05 amCoffee Break
11:05 am - 11:25 amSelected from Poster Abstracts: Kvido Strisovsky (Institute of Organic Chemistry and Biochemistry (IOCB), Czech Republic)
"A Novel Modular Route to Selective High-Affinity Mechanism-Based Inhibitors of Rhomboid Intramembrane Proteases"
11:25 am - 11:30 amDiscussion
11:30 am - 11:50 amSelected from Poster Abstracts: Galia Blum (Hebrew University of Jerusalem, Israel)
"Novel Methods to Study Cellular Localization of Protease Activity"
11:50 am - 11:55 amDiscussion
11:55 am - 12:20 pmCelia Schiffer (University of Massachusetts Medical School, USA)
"Constraining Evolution - Avoiding Drug Resistance: Lessons from Viral Proteases"
12:20 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmIntracellular Proteolysis in Cell Fate Decisions
Discussion Leaders: Rob Pike (La Trobe University, Australia) and Boris Turk (Jožef Stefan Institute, Slovenia)
6:00 pm - 6:25 pmMarius Lemberg (University of Heidelberg, Germany)
"Role of Intramembrane Proteases in the Control of Organelle Protein Homeostasis"
6:25 pm - 6:35 pmDiscussion
6:35 pm - 6:55 pmSelected from Poster Abstracts: Jemila Kester (Harvard University, USA)
"Proteolytic Control of the Mycobacterial Cell Cycle"
6:55 pm - 7:00 pmDiscussion
7:00 pm - 7:20 pmSelected from Poster Abstracts: Jean-Bernard Denault (Université de Sherbrooke, Canada)
"Caspase-Mediated Proteolysis of SNX1 and SNX2 Retromer Proteins"
7:20 pm - 7:25 pmDiscussion
7:25 pm - 7:50 pmGuy Salvesen (Sanford Burnham Prebys Medical Discovery Institute, USA)
"Protease Networks in Inflammatory Cell Death"
7:50 pm - 8:00 pmDiscussion
8:00 pmDinner
Friday
7:30 am - 8:30 amBreakfast
9:00 amDeparture
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