The 2019 FASEB Science Research Conference on Matricellular Proteins in Inflammation and Tissue Remodeling, July 14–19, 2019, Lisbon, Portugal

Each year, a series of Science Research Conferences (SRCs) are sponsored by The Federation of American Societies for Experimental Biology (FASEB), a non-profit federation of 29 research societies representing 130,000 scientists, that allows experimental biologists to meet in a relaxing, collegial atmosphere and explore new approaches to current research areas. Matricellular proteins were defined by Dr. Paul Bornstein in 1995 as a family of structurally diverse, modular secreted proteins that bind to both extracellular matrix molecules and cellular receptors to regulate a wide array of key cellular processes, including cell adhesion, migration, survival, proliferation, extracellular matrix organization, growth factor and protease regulation, and differentiation. Of importance are emerging data showing key roles for matricellular proteins in diseases through their roles in regulating tissue remodeling, angiogenesis, fibrosis, inflammation, immunity, metabolism, and development. Matricellular proteins are therapeutic targets for multiple diseases, including cardiovascular disease, cancer and metastasis, autoimmunity, neurogenesis and neuropathic pain, ocular diseases including inflammation, glaucoma, and macular degeneration, diabetes and diabetic complications, skeletal dysplasia and regeneration, and arthritis. The field has evolved from elucidating structure function activities of these complex proteins to identifying roles in diseases and the development of matricellular-targeted therapeutic interventions. The Matricellular Proteins in Inflammation and Tissue Remodeling conference was held in Lisbon, Portugal, 14-19 July 2019, at the Lisbon Marriott hotel. The goal of the conference was to bring together investigators in the field of matricellular proteins focusing on specific diseases and physiological systems and providing a forum for interdisciplinary exchange and discussions that led to dissemination of new ideas and information across several medical and basic science fields, create new opportunities for collaboration and cross-fertilization, and help to ensure the highest quality future research. This goal is important for all researchers in the field of matricellular proteins, but it is particularly important for young scientists, who may otherwise not have access to the depth of preceding knowledge or may become over-specialized in the absence of such interchanges. This interchange is a key component of the meeting, because it breaks the barriers of many traditional small meetings which are disease, organ, or molecular family focused. The biological functions and mechanisms of action of matricellular proteins are attracting increasing interest within the scientific community as several matricellular members have been identified as key regulators of tissue homeostasis, normal and pathological tissue remodeling, and inflammation. Matricellular proteins are making their way into clinical and translation studies as well. Dysregulation of their function is being increasingly recognized as central to the pathogenesis of several major diseases, including cardiovascular disease and cancer. These proteins function to regulate tissue remodeling: remodeling of vasculature and myocardium, angiogenesis, tumor progression, fibrogenesis, wound repair, hemostasis, diabetes, obesity, inflammation, innate and acquired immunity, synaptogenesis, and development and stem cell differentiation. At the conference, evidence for potential use of therapeutic strategies aimed at targeting or replicating the activity of CCN2 (Enrique Brandan, Chile; Andrew Leask, Canada), tenascin-C (Kim Midwood, UK), fibulin-7 (Susana de Vega, Japan), and thrombospondin 1 (Stephane Dedieu, France; Giulia Taraboletti, Italy; Laura Velazquez, France) were presented. The agonistic effects of CCN2 and antagonistic effects of CCN3 on multi-organ fibrosis and solid tumors and the use of CCN3-based therapeutic peptides for treatment were shown by Bruce Riser, USA. In addition, Jacqueline Hecht spoke about clinical trials to treat children with COMP mutations that cause a form of dwarfism. Together, these exciting findings establish the relevance of matricellular proteins in disease pathogenesis and treatment. The conference was organized into nine sessions, each focused on the physiology and/or disease of a specific physiological system (e.g., Matricellular Proteins in Cardiovascular Physiology and Disease, Matricellular Proteins in Remodeling of Connective Tissue and Fibrotic Disease) or on physiological process or specific application of matricellular proteins (e.g., Matricellular Proteins in Development, Matricellular Proteins and Biomaterials). In each session, there were 4-8 talks, for a total of 39 talks by invited speakers, who are recognized leaders in the field, and 14 presentations selected from the submitted abstracts. The keynote speaker Dr. Didier Stainier, Director at the Max Planck Institute for Heart and Lung Research in Bad Nauheim (Germany) presented a new paradigm in regulation of gene expression. Dr. Stainier described an mRNA-decay-dependent mechanism of upregulation of genes that exhibit sequence similarity with the mutated gene’s mRNA. This novel pathway of gene regulation is sequence-dependent and a part of the phenomenon of transcriptional adaptation. In addition to a better understanding of disease-causing mutations, these findings will greatly help in designing mutant alleles with minimal compensation. The attendees found this talk very stimulating and inspiring and relevant to everyone’s research activities. The talk generated a significant discussion about how these mechanisms may impact the matricellular protein field and was evaluated by the attendees as a great choice for a keynote presentation. This was reflected in the evaluation from the attendees (e.g., “…really liked that the Keynote talk was on a distinct topic—would be good to continue this in the future. Also liked having a keynote on basic cell/molecular biology research…”). The conference started with two sessions on Matricellular Proteins in Immunity, Inflammation, and Injury. The roles of matricellular proteins in regulation of immune cell functions, wound healing, and pain were discussed. Dr. Amy Bradshaw (MUSC) presented recent results highlighting the role of a matricellular protein SPARC in development of cardiac fibrosis. SPARC is produced by bone marrow-derived immune cells in response to injury in myocardium. Matricellular proteins are well-known regulators of fibrosis. Fibrosis of various organs accounts for nearly half of all death in developed countries and promotes metastasis and cancer growth. The conference continued with two sessions on their role in fibrosis and connective tissue diseases. Bruce Riser (BLR Bio LLC) discussed new developments in designing drugs based on CCN family of proteins that show the potential to threat and even reverse not only fibrosis, but also loss of organ function. The potential use of matricellular proteins to prevent scarring was discussed by Dr. Douglas W. Hamilton (The University of Western Ontario—London, CAN), who discovered a distinct pattern of expression of a matricellular protein periostin in gingival and palatal tissue. Gingiva does not scar, but palatal tissue is associated with severe scarring, and evidence showed a different role for the protein in these two tissues. Dr. Davy Vanhoutte (Cincinnati Children's Hospital Medical Center), who is one of the seven recipients of Travel Awards, discussed the mechanism of action and the role of Thrombospondin-3 (TSP-3) in myocardium. Out of five members of the Thrombospondin family, this protein is the least studied. The presented results not only shed light on its functions and properties but also redefine thrombospondin biology by uncovering that these proteins function as intracellular mediators of plasma membrane attachment complexes to regulate the dynamics of cellular remodeling and membrane stability. In the session on Matricellular Proteins and Biomaterials that took place on Tuesday, July 16, Dr. Yadong Wang (Cornell University) discussed the development of regenerative matrices for cardiac repair and vascular regeneration using the extracellular matrix proteins from regenerative species and organs. This innovative approach results in restoration of heart and vascular function superior to current approaches. The session on Matricellular Proteins in Aging and Metabolic Diseases encompassed discussions of matricellular proteins in metabolic dysfunction and cancers associated with metabolic changes, in aging heart, in stress-induced senescence, in neurodegenerative diseases, and in atherosclerosis. A novel signaling pathway by which TSP-1 regulates mitochondrial fission and the reactive oxygen species generation during hypoxia and ischemia reperfusion was presented by Dr. Amanda LeBlanc (University of Louisville), and a strategy to improve the heart function and to reverse coronary microvascular dysfunction in aging population by inhibiting TSP-1 was discussed. The Keynote session, Matricellular Proteins in Cardiovascular Physiology and Disease, held in the evening of Wednesday, July 17, informed the attendees of new insights into roles of TSP-1 and tenascin in aortic remodeling and myocardial tissue repair, respectively, as well as into regulation of TSP-1 by miRNA. Thursday, July 18 sessions were dedicated to the roles of matricellular proteins in cancer. Regulation of metastasis, fibrosis, cancer microenvironment, and cancer vasculature were discussed. Dr. Gertraud Orend (INSERM—Strasbourg, FRA) reported that tenascin C promotes metastasis through several complementary signaling mechanisms in both the stromal and the tumor cells. The conference was concluded with a session on Matricellular Proteins in Physiology and Diseases of Nervous System and Eye, during which the roles of matricellular proteins in ocular diseases such as glaucoma, age-related macular degeneration, and ocular inflammation were discussed. Two career development events were held during the lunch hours. One of them organized experts and trainees for an informal discussion by interests (Meet the Expert lunch) and was appreciated by the trainees (e.g., “I really enjoyed the lunch at which we had tables for specific matricellular proteins. I would like to see that continued.”). The second event brought together established investigators and the young investigators/trainees to discuss the career development issues. The event was also useful to young investigators, and this was reflected in their comments. The participants indicated that they benefited from discussing “grant seeking,” “publishing strategies,” and noted that “It was great to have the designated time for Career Development.” To support trainees’ and young investigators’ travel to the conference, six awards were given based on the evaluation of the posters and talks by conference faculty. Sukhbir Kaur (NCI), Jasmine Gajeton (Cleveland Clinic), and Thomas Loustau (Inserm U1109—Strasbourg, FRA) received the Conference Poster Awards. Davy Vanhoutte (Cincinnati Children's Hospital Medical Center) and Georgia Nikoloudaki (Western University—London, CAN) received the Conference Travel Award. Thomas Daubon (INSERM-GBM Team-Univ Bordeaux-PESSAC, FRA) received a Young Investigator Award, and Sophia Pantasis (ETH—Zürich, CHE) was awarded the Travel Award from the American Journal of Physiology Cell Physiology. Attendees of the matricellular proteins in tissue remodeling and inflammation conference, 14-19 July 2019, Lisbon, Portugal This meeting was supported by an array of public and private organizations including Cleveland Clinic (Cleveland, OH), The Company of Biologists, International Society for Matrix Biology, American Journal of Physiology (Cell Physiology), and AAAS Science Signaling. Funding for this conference was also made possible in part by 1R13HL147539-01 from the National Heart, Lung and Blood Institute. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the NIH; nor does mention by trade names, commercial practices, or organizations imply endorsement by the US Government.

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