Schlumberger Chair of Advanced Studies and Research, and Professor of Biochemistry and Cell Biology, Rice University
Rice University Wiess School of Natural Sciences - MS 102
George R. Brown Hall , E100E
Houston, TX 77251-1892
B.S. Biology University of Pennsylvania (1975)
Ph.D. Microbiology Temple University (1979)
Dr. Carson's laboratory is examining the expression and function of cell surface components that participate in and regulate cellular interactions in developing embryos and various tumor cell models. Following fertilization, embryos develop to a stage at which they acquire the ability to bind to and invade uterine tissue. This development reflects an increase in the expression of embryonic adhesion-promoting molecules. One class of embryonic adhesion-promoting molecules is heparan sulfate proteoglycans (HSPGs). Studies in both mouse and human model systems indicate that HSPGs and novel cell surface proteoglycan-binding proteins support embryo-uterine interactions at early stages of embryo attachment. Expression of both the HSPGs and their binding proteins persists through placental development and plays an important role in cartilage development. Studies of the patterns of expression of both HSPG core proteins, HS polysaccharides and various mouse lines in which genes encoding HS biosynthetic enzymes or protein cores demonstrate a critical role for HSPGs in cartilage and bone development and function. Similar HSPG-dependent interactions occur in a variety of tumor cell lines, including those of breast, melanoma and prostate. Various cell culture and animal models are used to determine the precise roles HSPGs play in normal development and tumor models.
A novel HSPG-binding protein (HIP) is expressed in a number of normal and malignant adult epithelia where it is proposed to play a similar proteoglycan-binding role. Structure-function and genetic approaches are used to understand the exact function of HIP and proteoglycans in implantation as well as in the physiology of adult tissues.
Another class of cell surface molecules, high molecular weight mucin glycoproteins, is expressed by many normal epithelial cells and at particularly high levels in various tumors. One mucin in particular, MUC1 is proposed to play an antiadhesive role and protect tumor cells from host immune surveillance. MUC1 is abundantly distributed at the apical aspect of the uterine epithelium under most conditions in a number of species, including mice and humans. In mice, MUC1 is markedly down-regulated at both the protein and mRNA level prior to the time of embryo attachment. This response appears to be critical to permit embryo attachment and is mediated by the action of ovarian steroid hormones, certain cytokines, and their receptors. Again, Molecular biological and molecular genetic approaches are used to understand the MUC1 expression in the context of embryo attachment and in breast and prostate cancer models.