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Plasminogen Activation and Extracellular Proteolysis

Gordon Research Conference

Extracellular Proteolysis in Human Disease: Cutting-Edge Research, Emerging Therapeutics, and Clinical Outcomes

February 18 - 23, 2024

Chairs

and

Vice Chairs

and

Four Points Sheraton / Holiday Inn Express

1050 Schooner Drive

Ventura, California, United States

Venue and Travel Information

Conference Description

The Plasminogen Activation and Extracellular Proteolysis GRC is a premier, international scientific conference focused on advancing the frontiers of science through the presentation of cutting-edge and unpublished research, prioritizing time for discussion after each talk and fostering informal interactions among scientists of all career stages. The conference program includes a diverse range of speakers and discussion leaders from institutions and organizations worldwide, concentrating on the latest developments in the field. The conference is five days long and held in a remote location to increase the sense of camaraderie and create scientific communities, with lasting collaborations and friendships. In addition to premier talks, the conference has designated time for poster sessions from individuals of all career stages, and afternoon free time and communal meals allow for informal networking opportunities with leaders in the field.

The theme of the 2024 Plasminogen Activation and Extracellular Proteolysis GRC will be Cutting-Edge Research, Emerging Therapeutics, and Clinical Outcomes. The focus of this GRC will be on extracellular proteolysis, mediated by plasminogen and its activators, matrix metalloproteases (MMPs), and other extracellular proteases, that operates at the interface of cell-cell, cell-fluid, and cell-matrix contacts. Dysfunction of the plasminogen activation and MMP system precipitates the etiology of various human diseases, ranging from thrombotic complications to neurodegeneration, from metabolic dysfunction to aging, and from infection to cancer. This meeting serves as a forum to showcase exciting discoveries in the field of plasminogen activation, MMPs, and other key extracellular proteases, as well as protease-based molecular imaging, diagnosis, and therapeutics. The GRC brings together leading researchers in this multidisciplinary and expanding field of scientific research for a highly personal and interactive meeting in a casual atmosphere. This conference has an excellent record of stimulating thought-provoking discussions, establishing collegial interactions, and launching new collaborations to advance our understanding of the role of extracellular proteolysis in biological functions, disease mechanisms, and new treatments.

This GRC also provides excellent avenues for budding investigators and offers ample opportunities for them to interact with world-renowned scientists. The speakers of the Late Breaking Topics session will be selected from the conference abstracts based on their merit.* The conference will also offer special awards for the best posters presented by students and postdoctoral fellows. Minority attendees can seek financial support through the Carl Storm Underrepresented Minority Fellowship. Please join us in 2024!

*Applications for this meeting must be submitted by January 21, 2024. Abstracts must be submitted by December 15, 2023, to be eligible for consideration of oral presentations.

Related Meeting

This GRC will be held in conjunction with the "Plasminogen Activation and Extracellular Proteolysis" Gordon Research Seminar (GRS). Those interested in attending both meetings must submit an application for the GRS in addition to an application for the GRC. Refer to the associated GRS program page for more information.

Conference Program

Sunday
2:00 pm - 9:00 pm	Arrival and Check-in
6:00 pm - 7:00 pm	Dinner
7:30 pm - 7:40 pm	Introductory Comments by GRC Staff / Welcome and Introduction from the Chairs
7:40 pm - 9:30 pm	Keynote Session: Evolving Functionality of the Fibrinolytic System Through the Decades Discussion Leaders: and
7:40 pm - 7:45 pm	Opening Remarks
7:45 pm - 8:05 pm	Introduction by Discussion Leader
8:05 pm - 8:40 pm	"Plasminogen Receptors: The More We Learn, The More We Question"
8:40 pm - 8:50 pm	Discussion
8:50 pm - 9:20 pm	"Plasminogen Activation and Extracellular Proteolysis: From Bedside to Bench and Back Again"
9:20 pm - 9:30 pm	Discussion
Monday
7:30 am - 8:30 am	Breakfast
8:30 am - 9:00 am	Group Photo
9:00 am - 12:30 pm	Thrombotic Disorders: Basic Research and Its Impact in Clinical Management Discussion Leaders: and
9:00 am - 9:05 am	Introduction by Discussion Leader
9:05 am - 9:25 am	"Meeting the tPA Challenge: Use of Viscoelastic Tests to Guide Trauma Care"
9:25 am - 9:35 am	Discussion
9:35 am - 9:55 am	"The Story of Tranexamic Acid in Acute Severe Bleeding"
9:55 am - 10:05 am	Discussion
10:05 am - 10:25 am	"A Novel Antiplasmin Inhibitor: From Preclinical Study to First in Human Evaluation"
10:25 am - 10:35 am	Discussion
10:35 am - 11:00 am	Coffee Break
11:00 am - 11:20 am	"Clinical Manifestation of Plasminogen Deficiency"
11:20 am - 11:30 am	Discussion
11:30 am - 11:50 am	"Three Distinct Clot Lysis Assays to Detect Activities of Alpha2 Antiplasmin, PAI-1 and TM/TAFI: Their Applications to Assess TXA Necessity, PAI-1 Deficiency and Soluble TM Function in Plasma"
11:50 am - 12:00 pm	Discussion
12:00 pm - 12:10 pm	"Host Fibrinolytic Deficiencies Enhance Pathogen Colonization in the Catheterized Bladder Environment and Promote Systemic Dissemination"
12:10 pm - 12:15 pm	Discussion
12:15 pm - 12:25 pm	"PAI-1 Requires Sortilin-Related Receptor 1 to Exert Its Profibrotic Effects"
12:25 pm - 12:30 pm	Discussion
12:30 pm - 1:30 pm	Lunch
1:30 pm - 4:00 pm	Free Time
3:00 pm - 4:00 pm	The GRC Power Hour™ The GRC Power Hour™ is designed to address diversity and inclusion in the scientific workplace by providing a safe environment for informal and meaningful conversations amongst colleagues of all career stages. The program supports the professional growth of all members of our communities, including ethnicity, race and/or gender identity by providing an open forum for discussion and mentoring. Organizers: and
4:00 pm - 6:00 pm	Poster Session
6:00 pm - 7:00 pm	Dinner
7:30 pm - 9:30 pm	Proteases in Metabolic Diseases and Aging Discussion Leaders: and
7:30 pm - 7:35 pm	Introduction by Discussion Leader
7:35 pm - 7:55 pm	"Evolutionary Advantage of Heterozygous PAI-1 Deficiency in Humans"
7:55 pm - 8:05 pm	Discussion
8:05 pm - 8:25 pm	"Senescent Cells: Conversations with Their Neighbors"
8:25 pm - 8:35 pm	Discussion
8:35 pm - 8:55 pm	"Plasminogen and uPA in the Pathogenesis of Obesity and Metabolic Syndrome"
8:55 pm - 9:00 pm	Discussion
9:00 pm - 9:10 pm	"MT1-MMP: A New Therapautic Target of Obesity and Diabetes"
9:10 pm - 9:15 pm	Discussion
9:15 pm - 9:25 pm	"The Reciprocal Relationship Between Coagulation Factor VIII and apoB-Lipoprotein"
9:25 pm - 9:30 pm	Discussion
Tuesday
7:30 am - 8:30 am	Breakfast
9:00 am - 12:30 pm	Inflammatory Diseases and Cancer: MMP, tPA and Plasminogen Discussion Leaders: and
9:00 am - 9:05 am	Introduction by Discussion Leader
9:05 am - 9:25 am	"Targeting Pathophysiological Proteolytic Networks"
9:25 am - 9:35 am	Discussion
9:35 am - 9:55 am	"Metalloprotease Inhibitors as Regulators of Tissue Stem Cell Fate"
9:55 am - 10:05 am	Discussion
10:05 am - 10:25 am	"Structure-Function Studies of a Novel Bacterial MMP Inhibitor and of Celiacase: A Promising Therapeutic Agent for Celiac Disease"
10:25 am - 10:35 am	Discussion
10:35 am - 11:00 am	Coffee Break
11:00 am - 11:20 am	"Multiomic Profiling of Fibrin-Induced Microglia Functions in Neurodegeneration"
11:20 am - 11:30 am	Discussion
11:30 am - 11:50 am	"Plasminogen Activator Receptors as Regulators of Cell Physiology"
11:50 am - 12:00 pm	Discussion
12:00 pm - 12:20 pm	"Membrane-Anchored Serine Proteases in Epithelial Homeostasis and Disease"
12:20 pm - 12:30 pm	Discussion
12:30 pm - 1:30 pm	Lunch
1:30 pm - 4:00 pm	Free Time
4:00 pm - 6:00 pm	Poster Session
6:00 pm - 7:00 pm	Dinner
7:30 pm - 9:30 pm	Proteases in Infection and Immunity Discussion Leaders: and
7:30 pm - 7:35 pm	Introduction by Discussion Leader
7:35 pm - 7:55 pm	"Neutrophil Activation in Thromboinflammatory Syndromes"
7:55 pm - 8:05 pm	Discussion
8:05 pm - 8:25 pm	"Group A Streptococcal Interactions with Blood System Components Revealed Through Live Imaging"
8:25 pm - 8:35 pm	Discussion
8:35 pm - 8:55 pm	"Recent Advances Identifying Structural Requirements for Accelerated Plasminogen Activation by Group A Streptococcus Plasminogen-Binding Proteins"
8:55 pm - 9:00 pm	Discussion
9:00 pm - 9:10 pm	"Targeting of Factor XII by CpaA, A Secreted Acinetobacter Glycoprotease Impairs Contact Activation and Neutrophil Functions"
9:10 pm - 9:15 pm	Discussion
9:15 pm - 9:25 pm	"Targeting the uPAR System in Pancreatic Cancer: A Novel Antibody-Drug-Conjugate Approach Eliciting Tumor Regression and Immune Activation"
9:25 pm - 9:30 pm	Discussion
Wednesday
7:30 am - 8:30 am	Breakfast
9:00 am - 12:30 pm	Cerebrovascular Diseases: Imaging, Function and Mechanism Discussion Leaders: and
9:00 am - 9:05 am	Introduction by Discussion Leader
9:05 am - 9:25 am	"Fibrin in Neurological Diseases: Mechanisms, Imaging, Therapeutics"
9:25 am - 9:35 am	Discussion
9:35 am - 9:55 am	"tPA’s Role in Neurovascular Function, Dysfunction and Alzheimer Pathology"
9:55 am - 10:05 am	Discussion
10:05 am - 10:25 am	"Role of tPA in Metabolism: Implications in Stroke Therapy"
10:25 am - 10:35 am	Discussion
10:35 am - 11:00 am	Coffee Break
11:00 am - 11:20 am	"Latest Insights into tPA-Mediated NMDA Receptor Signaling via a Specific Knock-In Model"
11:20 am - 11:30 am	Discussion
11:30 am - 11:50 am	"Targeting the Plasma Contact System to Ameliorate Vascular Dysfunction and Inflammation in Alzheimer’s Disease"
11:50 am - 12:00 pm	Discussion
12:00 pm - 12:10 pm	"Glunomab: AN mAb Preventing Blood-Brain Barrier Disruption Caused by Endogenous tPA and Thrombolytic Drugs Following Ischemic Stroke"
12:10 pm - 12:15 pm	Discussion
12:15 pm - 12:25 pm	"Fibrin Promotes Oxidative Stress and Neuronal Loss in Traumatic Brain Injury via Innate Immune Activation"
12:25 pm - 12:30 pm	Discussion
12:30 pm - 1:30 pm	Lunch
1:30 pm - 4:00 pm	Free Time
4:00 pm - 6:00 pm	Poster Session
6:00 pm - 7:00 pm	Dinner
7:30 pm - 9:30 pm	Proteases in Musculoskeletal Diseases Discussion Leaders: and
7:30 pm - 7:35 pm	Introduction by Discussion Leader
7:35 pm - 7:55 pm	"Integrated Forward and Reverse Degradomics of Human Diseases"
7:55 pm - 8:05 pm	Discussion
8:05 pm - 8:25 pm	"Metalloproteases ADAMTS13 and ADAMTS7: Substrate Processing and Regulation"
8:25 pm - 8:35 pm	Discussion
8:35 pm - 8:55 pm	"An Update of Plasminogen's Role in Orthopedic Injury"
8:55 pm - 9:00 pm	Discussion
9:00 pm - 9:10 pm	"Unveiling a Novel Cleavage Site: Plasmin-Resistant tPA Isoforms and Their Functional Roles"
9:10 pm - 9:15 pm	Discussion
9:15 pm - 9:25 pm	"Critical Role of Fibrinolysis in Hematopoietic Recovery After Myelosuppression"
9:25 pm - 9:30 pm	Discussion
Thursday
7:30 am - 8:30 am	Breakfast
8:30 am - 9:00 am	Business Meeting Nominations for the Next Vice Chair(s); Complete the GRC Evaluation Forms; Election of the Next Vice Chair(s)
9:00 am - 12:30 pm	Emerging Technologies to Dissect Protease Function Discussion Leaders: and
9:00 am - 9:05 am	Introduction by Discussion Leader
9:05 am - 9:25 am	"Application of Small Molecule and Biological Probes in the Discovery and Quantitation of IBD-Associated Proteases"
9:25 am - 9:35 am	Discussion
9:35 am - 9:55 am	"Proteolysis and Blood Brain Barrier Changes in Alzheimer’s Disease"
9:55 am - 10:05 am	Discussion
10:05 am - 10:25 am	"Fibrinolysis and Thrombolysis in Thrombus Resolution"
10:25 am - 10:35 am	Discussion
10:35 am - 11:00 am	Coffee Break
11:00 am - 11:20 am	"Novel Blood-Compatible Macromolecular Sensors for Proteases"
11:20 am - 11:30 am	Discussion
11:30 am - 11:50 am	"Bioinspired Nanotherapeutics for Targeted Fibrinolysis"
11:50 am - 12:00 pm	Discussion
12:00 pm - 12:20 pm	"Deep Mutational Scanning to Map PAI-1 Functional Specificity and Evolution"
12:20 pm - 12:30 pm	Discussion
12:30 pm - 1:30 pm	Lunch
1:30 pm - 4:00 pm	Free Time
4:00 pm - 6:00 pm	Poster Session
6:00 pm - 7:00 pm	Dinner
7:30 pm - 9:30 pm	Proteases in Cutting-Edge Therapeutics Discussion Leaders: and
7:30 pm - 7:45 pm	General Discussion
7:45 pm - 7:50 pm	Introduction by Discussion Leader
7:50 pm - 8:10 pm	"Development of an Orally Active Small Molecule Inhibitor of PAI-1 for the Treatment of Systemic Sclerosis"
8:10 pm - 8:20 pm	Discussion
8:20 pm - 8:40 pm	"Stopping Pancreatic Cancer in Its Tracks: Anti-Metastatic and Anti-Immunosuppressive Effects of a Selective uPA Inhibitor in Preclinical Models"
8:40 pm - 8:50 pm	Discussion
8:50 pm - 9:10 pm	"Plasminogen Deficiency and the Potential for Plasminogen Supplementation in Treatment of Pleural Space Infections"
9:10 pm - 9:20 pm	Discussion
9:20 pm - 9:30 pm	Closing Remarks
Friday
7:30 am - 8:30 am	Breakfast
9:00 am	Departure

Contributors

Funding for this conference was made possible (in part) by 1R13HL172575-01 from the National Heart Lung and Blood Institute (NHLBI). The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.

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