Hyaluronan (HA) is a glycosaminoglycan composed of alternating subunits of glucuronic acid and N-acetyglucosamine. Despite the chemical simplicity of HA, this molecule has been implicated in numerous processes, including: 1) Maintenance of tissue integrity, 2) Cell adhesion and trafficking, 3) Homotypic and heterotypic cell-cell interactions, and 4) Cell activation and proliferation. Our interest is the role of HA in the immune system and how manipulation of HA can be used to modulate immunological responses.
Studies that directly measure the biological functions of HA are generally lacking due to the paucity of HA inhibitors. In order to assess the immunological roles of HA in vitro and in vivo, we have developed a novel peptide inhibitor of HA (termed "Pep-1") using phage display technology. We have shown that: 1) HA has a role in the trafficking of leukocytes to and from inflamed skin, 2) HA supports the in vivo maturation of dendritic cells, 3) Dendritic cells and activated T cells express HA on their surface, and 4) HA has a potential role in antigen presentation. Results from our investigations show that HA has multiple roles in the immune response.
On going efforts in our laboratory include dissecting the molecular and biochemical pathways involved in HA-mediated T cell activation and proliferation. Because the biological activity of HA is related to its relative molar mass, we are also interested in evaluating the impact of HA co-polymers of defined size on T cell biology in vitro and in vivo.
A number of studies have suggested that HA may have multiple roles in tumor biology, including: 1) Angiogenesis, 2) Tumor cell invasion, and 3) Metastasis. Based on the potential importance of HA in cancer, we have initiated studies to assess the role of HA in malignant melanoma. Our goals for these studies are to determine: 1) Factors in the tumor microenvironment that regulate HA synthesis and degradation, 2) The relevant HA receptors involved in the progression of malignant melanoma, and 3) To develop HA-targeted probes for in vivo imaging and therapy.
Other projects in our laboratory are aimed at developing new tools and methods to study the functions of other glycosaminoglycans (e.g., dermatan sulfate, keratin sulfate) in the immune response and tumor biology.
RESEARCH INTERESTS
Skin Biology
Immunology
RECENT PUBLICATIONS
Mummert DI, Ellinger L, Takashima A, Mummert ME, "Involvement of hyaluronan in epidermal Langerhans cell migration in vivo." J Dermatol Sci, 33:91-97, 2003
Mummert DI, Takashima A, Mummert ME, "Langerhans cells in CD44-deficient mice emigrate from the epidermis but fail to reach the lymph nodes after hapten application." J Invest Dermatol, 122:846-847, 2004
Mummert ME, "Immunological roles of hyaluronan." Immunol Res, 31:189-206, 2005
Mahaffey CL, Mummert ME, "Hyaluronan synthesis is required for IL-2 mediated T cell proliferation." J Immunol, In Press
SIGNIFICANT PUBLICATIONS
Mummert ME, Mohamadzadeh M, Mummert DI, Mizumoto N, Takashima A, "Development of a peptide inhibitor of hyaluronan-mediated leukocyte trafficking" Journal of Experimental Medicine, 192:769-779, 2000
Mummert ME, Mummert D, Edelbaum D, Matsue H, Takashima A, "Synthesis and surface expression of hyaluronan by dendritic cells and its potential role in antigen presentation." J Immunol, 169:4322-4331, 2002
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