Kenneth Adolph

The focus of my research is on the thrombospondin proteins, which are extracellular proteins involved in a variety of fundamental biological functions and which, when malfunctioning, can result in human diseases and disorders. Thrombospondins have been found to have important biological roles in blood vessel formation, immune function, cardiovascular function, wound healing, bone and collagen formation, musculoskeletal function, and nerve cell connections. If any of these activities of the thrombospondin proteins are not normal, diseases and disorders can result that include tumor progression/metastasis, cardiovascular disease, abnormal skeletal development, osteoporosis, degenerative joint disease, and neurological disorders. Understanding how thrombospondin proteins act is crucial to developing therapies to cure or alleviate these abnormal conditions.

My research concerns the thrombospondin proteins (TSPs), a family of large extracellular proteins with complex and characteristic protein domain structures. Through the protein domains, the thrombospondins (TSP1, 2, 3, 4, 5/COMP) interact with cells and extracellular proteins to mediate cell-extracellular matrix interactions and cell-cell interactions, as well as tissue remodeling, cell proliferation, and cell migration. Because of these interactions, roles for human TSPs have been identified in a variety of fundamental biological functions. These roles include an involvement in angiogenesis, immune function, cardiovascular function, wound healing, collagen formation, bone formation, musculoskeletal function, and synaptogenesis. Due to these various fundamental roles, thrombospondin malfunction is an important factor in human diseases and disorders that include tumor progression/metastasis, cardiovascular disease, skeletal dysplasia, osteoporosis, degenerative joint disease, and neurological disorders.

A particular research interest is to investigate similarities and differences in the structure and function of invertebrate thrombospondins compared to human thrombospondins to more fully understand the roles of TSPs. At present, there is no published information about the functions of invertebrate thrombospondins, and so my studies open a new area of research. I have found that TSPs are widely distributed in invertebrate phyla including Mollusca, Cnidaria, Echinodermata, Arthropoda, and Chordata, which suggests that invertebrate TSPs are likely to have important biological roles. In addition to invertebrate thrombospondins that have structural similarity to human TSPs, unique Mega-TSPs have been detected in a variety of invertebrate species.

Another interest is in the metaxin proteins. The metaxins (metaxins 1, 2, and 3) are a broadly distributed group of proteins found in humans, other vertebrates, and invertebrates, and have also been detected in fungi, protists, plants, and bacteria. The metaxins are smaller and less complex proteins than thrombospondin proteins, with about 300 amino acids (compared to 1000 for the TSPs) and only two major protein domains. In humans, roles for metaxins 1 and 2 have been implicated in the process of protein import into mitochondria. In connection with human disease, mutations in the metaxin 2 gene are associated with a premature aging syndrome (mandibuloacral dysplasia, or MAD), potentially due to mitochondrial dysfunction.