Daniel Carson, Ph.D.
Adjunct Professor
Dean, Schlumberger Chair of Advanced Studies and Research, and Professor of Biochemistry and Cell Biology, Rice University
Carson
Phone: (713) 348-3350
Fax: (713) 348-6149
Email: dcarson@rice.edu
Address:
Rice University Wiess School of Natural Sciences - MS 102
203 Keck Hall
P.O. Box 1892
Houston, TX 77251-1892
Education
- B.S. - University of Pennsylvania
- Ph.D. - Temple University
- Postdoctoral - Johns Hopkins University School of Medicine
Research Interests
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.
Current Projects
- Molecular aspects of implantation - Expression and function of cell surface components at points of interaction between embryos and uterine cells in mice and human model systems
- Regulation of mucin glycoprotein expression and function - Molecular biological and genetic approaches are used to study expression of the key barrier molecules, mucins, in response to models, cytokines and microbial challenges. Animal models as well as human breast and prostate cancer are being studied.
- Heparan sulfate proteoglycan (HSPG) expression and function in cartilage development - The role that the HSPG, perlecan, plays in development and maintenance of cartilage is being studied using cell biological and molecular genetic techniques.
- Heparin/heparan sulfate interacting protein (HIP/L29) expression and function - The roles that HIP plays in cell adhesion, control of blood coagulation and in reproduction are being studied by various approaches.
Research Group
- Catherine Kirn-Safran, Ph.D. - Research Assistant Professor (Ph.D., University Louis Pasteur, France). HIP/L29 expression and function in mice; development of transgenic mouse models.
- Sonia D'Souza, M.S. - Graduate Student (M.S., University of Mumbai, India). Role of heparin interacting protein (HIP) in biochemical aspects of growth factor delivery and activity.
- Neeraja Dharmaraj, M.S. - Graduate Student (M.S., Osmania University, India). MUC1 expression by inhibitors of metalloproteinases.
- John O'Connor, M.S. - Graduate Student (M.S., West Chester University). Regulation of MUC1 gene expression in prostate cancer cells.
- Peng (Paul) Wang, M.S. - Graduate Student (M.S., East China Normal University, China). Gene activation by MUC1 signaling.
- JoAnne Julian, B.S. - Scientist (B.S., Trinity University). Embryo implantation in mouse and human models.
- Rob Long, B.S. - Research Associate III (B.S., University of Delaware). In vitro studies of cell growth and differentiation, protein profiling using mass spectroscopy and HPLC techniques.
- Dan Oristian, B.A. - Graduate Student (B.A., University of Delaware). Use of ribozymes and siRNA in gene knockdown applications in ES cells and preimplantation embryos.
Selected Publications
- D'Souza SS, Fazleabas AT, Banerjee P, et al. Decidual heparanase activity is increased during pregnancy in the baboon (Papio anubis) and in in vitro decidualization of human stromal cells. Biol Reprod. 2008;78(2):316–323.
- Farach-Carson MC, Brown AJ, Lynam M, Safran JB, Carson DD. A novel peptide sequence in perlecan domain IV supports cell adhesion, spreading and FAK activation. Matrix Biol. 2008;27(2):150–160.
- Kirn-Safran CB, D'Souza SS, Carson DD. Heparan sulfate proteoglycans and their binding proteins in embryo implantation and placentation. Semin Cell Dev Biol. 2008;19(2):187–193.
- Wang P, Julian JA, Carson DD. The MUC1 HMFG1 glycoform is a precursor to the 214D4 glycoform in the human uterine epithelial cell line, HES. Biol Reprod. 2008;78(2):290–298.
- Brayman MJ, Dharmaraj N, Lagow E, Carson DD. MUC1 expression is repressed by protein inhibitor of activated signal transducer and activator of transcription-y. Mol Endocrinol. 2007;21(11):2725–2737.
- D'Souza SS, Daikoku T, Farach-Carson MC, Carson DD. Heparanase expression and function during early pregnancy in mice. Biol Reprod. 2007;77(3):433–441.
- Farach-Carson MC, Carson DD. Perlecan--a multifunctional extracellular proteoglycan scaffold. Glycobiology. 2007;17(9):897–905.
- Kirn-Safran CB, Oristian DS, Focht RJ, Parker SG, Vivian JL, Carson DD. Global growth deficiencies in mice lacking the ribosomal protein HIP/RPL29. Dev Dyn. 2007;236(2):447–460.
- O'Connor JC, Farach-Carson MC, Schneider CJ, Carson DD. Coculture with prostate cancer cells alters endoglin expression and attenuates transforming growth factor-beta signaling in reactive bone marrow stromal cells. Mol Cancer Res. 2007;5(6):585–603.
- Brayman MJ, Julian JA, Mulac-Jericevic B, Conneely OM, Edwards DP, Carson DD. Progesterone receptor isoforms A and B differentially regulate MUC1 expression in uterine epithelial cells. Mol Endocrinol. 2006;20(10):2278–2291.
- Carson DD, Julian JA, Lessey BA, Prakobphol A, Fisher SJ. MUC1 is a scaffold for selectin ligands in the human uterus. Front Biosci. 2006;11:2903–2908.
- Gomes RRJ, Joshi SS, Farach-Carson MC, Carson DD. Ribozyme-mediated perlecan knockdown impairs chondrogenic differentiation of C3H10T1/2 fibroblasts. Differentiation. 2006;74(1):53–63.
- Gomes RRJ, Van Kuppevelt TH, Farach-Carson MC, Carson DD. Spatiotemporal distribution of heparan sulfate epitopes during murine cartilage growth plate development. Histochem Cell Biol. 2006;126(6):713–722.
- Liu J-J, Huang BH, Zhang J, Carson DD, Hooi SC. Repression of HIP/RPL29 expression induces differentiation in colon cancer cells. J Cell Physiol. 2006;207(2):287–292.
- Muir C, Chung LWK, Carson DD, Farach-Carson MC. Hypoxia increases VEGF-A production by prostate cancer and bone marrow stromal cells and initiates paracrine activation of bone marrow endothelial cells. Clin Exp Metastasis. 2006;23(1):75–86.
- Yang W, Gomes RR, Brown AJ, et al. Chondrogenic differentiation on perlecan domain I, collagen II, and bone morphogenetic protein-2-based matrices. Tissue Eng. 2006;12(7):2009–2024.
- Al-Shami R, Sorensen ES, Ek-Rylander B, Andersson G, Carson DD, Farach-Carson MC. Phosphorylated osteopontin promotes migration of human choriocarcinoma cells via a p70 S6 kinase-dependent pathway. J Cell Biochem. 2005;94(6):1218–1233.
- Carson DD. Uterine sensing of the embryo. Proc Natl Acad Sci U S A. 2005;102(24):8397–8398.
- Farach-Carson MC, Hecht JT, Carson DD. Heparan sulfate proteoglycans: key players in cartilage biology. Crit Rev Eukaryot Gene Expr. 2005;15(1):29–48.
- Hecht JT, Hayes E, Haynes R, et al. Differentiation-induced loss of heparan sulfate in human exostosis derived chondrocytes. Differentiation. 2005;73(5):212–221.
- Julian JA, Enders AC, Fazleabas AT, Carson DD. Compartmental distinctions in uterine Muc-1 expression during early pregnancy in cynomolgous macaque (Macaca fascicularis) and baboon (Papio anubis). Hum Reprod. 2005;20(6):1493–1503.
- O'Connor JC, Julian J, Lim SD, Carson DD. MUC1 expression in human prostate cancer cell lines and primary tumors. Prostate Cancer Prostatic Dis. 2005;8(1):36–44.
- Savore C, Zhang C, Muir C, et al. Perlecan knockdown in metastatic prostate cancer cells reduces heparin-binding growth factor responses in vitro and tumor growth in vivo. Clin Exp Metastasis. 2005;22(5):377–390.
- Tang M, Mikhailik A, Pauli I, et al. Decidual differentiation of stromal cells promotes Proprotein Convertase 5/6 expression and lefty processing. Endocrinology. 2005;146(12):5313–5320.
- Yang WD, Gomes RRJ, Alicknavitch M, Farach-Carson MC, Carson DD. Perlecan domain I promotes fibroblast growth factor 2 delivery in collagen I fibril scaffolds. Tissue Eng. 2005;11(1-2):76–89.