All Publications

  • Hyaluronan in the Pathogenesis of Acute and Post-Acute COVID-19 Infection. Matrix biology : journal of the International Society for Matrix Biology Barnes, H. W., Demirdjian, S., Haddock, N. L., Kaber, G., Martinez, H. A., Nagy, N., Karmouty-Quintana, H., Bollyky, P. L. 2023


    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as the cause of a global pandemic. Infection with SARS-CoV-2 can result in COVID-19 with both acute and chronic disease manifestations that continue to impact many patients long after the resolution of viral replication. There is therefore great interest in understanding the host factors that contribute to COVID-19 pathogenesis. In this review, we address the role of hyaluronan (HA), an extracellular matrix polymer with roles in inflammation and cellular metabolism, in COVID-19 and critically evaluate the hypothesis that HA promotes COVID-19 pathogenesis. We first provide a brief overview of COVID-19 infection. Then we briefly summarize the known roles of HA in airway inflammation and immunity. We then address what is known about HA and the pathogenesis of COVID-19 acute respiratory distress syndrome (COVID-19 ARDS). Next, we examine potential roles for HA in post-acute SARS-CoV-2 infection (PASC), also known as "long COVID" as well as in COVID-associated fibrosis. Finally, we discuss the potential therapeutics that target HA as a means to treat COVID-19, including the repurposed drug hymecromone (4-methylumbelliferone). We conclude that HA is a promising potential therapeutic target for the treatment of COVID-19.

    View details for DOI 10.1016/j.matbio.2023.02.001

    View details for PubMedID 36750167

  • Pericellular hyaluronan modulates IL-2 responsiveness through CD44 Martinez, H., Marshall, P. L., Kaber, G., Nagy, N., Bollyky, P. L. AMER ASSOC IMMUNOLOGISTS. 2020
  • Hyaluronan synthesis inhibition impairs antigen presentation and delays transplantation rejection. Matrix biology : journal of the International Society for Matrix Biology Marshall, P. L., Nagy, N. n., Kaber, G. n., Barlow, G. L., Ramesh, A. n., Xie, B. J., Linde, M. H., Haddock, N. L., Lester, C. A., Tran, Q. L., de Vries, C. n., Hargil, A. n., Malkovskiy, A. n., Gurevich, I. n., Martinez, H. A., Kuipers, H. F., Yadava, K. n., Zhang, X. n., Evanko, S. P., Gebe, J. A., Wang, X. n., Vernon, R. B., de la Motte, C. n., Wight, T. N., Engleman, E. G., Krams, S. M., Meyer, E. n., Bollyky, P. L. 2020


    A coat of pericellular hyaluronan surrounds mature dendritic cells (DC) and contributes to cell-cell interactions. We asked whether 4-methylumbelliferone (4MU), an oral inhibitor of HA synthesis, could inhibit antigen presentation. We find that 4MU treatment reduces pericellular hyaluronan, destabilizes interactions between DC and T-cells, and prevents T-cell proliferation in vitro and in vivo. These effects were observed only when 4MU was added prior to initial antigen presentation but not later, consistent with 4MU-mediated inhibition of de novo antigenic responses. Building on these findings, we find that 4MU delays rejection of allogeneic pancreatic islet transplant and allogeneic cardiac transplants in mice and suppresses allogeneic T-cell activation in human mixed lymphocyte reactions. We conclude that 4MU, an approved drug, may have benefit as an adjunctive agent to delay transplantation rejection.

    View details for DOI 10.1016/j.matbio.2020.12.001

    View details for PubMedID 33290836