Dr. Daniel Carson

Trustees Distinguished Professor
Chairperson

Contact

Carson

Office: 118C Wolf Hall

Mailing address:
Dept. of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716

Phone: (302) 831-6977
Fax: (302) 831-1033
E-mail: dcarson@udel.edu

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Education

B.S.: University of Pennsylvania
Ph.D.: Temple University
Postdoctoral: Johns Hopkins University School of Medicine

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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.

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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.

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Teaching

• BISC 665* - Advanced Molecular Biology & Genetics
• BISC 806 - Topics in Extracellular Matrix Biology

*Course web site available through MyCourses

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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.

The Laboratory for Endocrine and Extracellular Matrix Biology

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Selected Publications

Kirn-Safran, C.B., D'Souza, S.S., and Carson, D.D. Hepran sulfate proteoglycans and their binding proteins in embryo implantation and placentation. Semin. Cell Dev. Biol., 19:187-193, 2008.

Wang, P., Julian, J.J., and Carson, D.D. The MUC1 HMFG1 glycoform is a precursor to the 214D4 glycoform in the human uterine epithelial cell line, HES. Biol. Reprod., 78:290-298, 2008.

D'Souza, S.S., Fazleabas, A.T., Banerjee, P., Sherwin, R.A., Sharkey, A.M., and Carson DD. Decidual heparanase activity is increased during pregnancy in the baboon (papio anubis) and following decidualization of human stromal cells in vitro. Biol. Reprod., 78:316-323, 2008.

Farach-Carson, M.C., Brown, A.J., Lynam, M., Safran, J.B., and Carson, D.D. A novel peptide sequence in perlecan domain IV supports cell adhesion and spreading. Matrix Biology, 27:150-160, 2008.

Brayman, M.J., Dharmaraj, N., Lagow, E., and Carson, D.D. MUC1 expression is repressed by PIASy. Mol. Endocrinol., 21:2725-2737, 2007.

Farach-Carson, M.C. and Carson, D.D. Perlecan: A multifunctional extracellular proteoglycan scaffold. Glycobiology, 17:897-905, 2007.

D'Souza, S.S., Daikoku, T., Farach-Carson, M.C., and Carson, D.D. Heparanase-1 expression and function during early pregnancy in mice. Biol. Reprod., 77:433-442, 2007.

O'Connor, J.C., Farach-Carson, M.C., Schneider, C.J., and Carson, D.D. Coculture with prostate cancer cells alters endoglin expression and attenuates transforming growth factor-beta signaling in reactive bone marrow stromal cells. Mol. Cancer Res., 5:585-603, 2007.

Kirn-Safran, C.B., Oristian, D.S., Focht, R.J., Parker, S.G., Vivian, J.L., and Carson, D.D. Global growth deficiencies in mice lacking the ribosomal protein HIP/RPL29. Dev. Dyn., 236:447-460, 2007.

Carson, D.D., Julian, J., Lessey, B.A., Prakobphol, A., and Fisher, S.J. MUC1 is a scaffold for selectin ligands in the human uterus. Front. Biosci., 11:2903-2908, 2006.

Gomes, R.R., Van Kuppevelt, T.H., Farach-Carson, M.C., and Carson, D.D. Spatiotemporal distribution of heparan sulfate epitopes during murine cartilage growth plate development. Histochem Cell Biol., 126:713-722, 2006.

Muir, C., Chung, L.W., Carson, D.D., and Farach-Carson, M.C. 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, 23(1):75-86, 2006.

Brayman, M.J., Julian, J., Mulac-Jericevic, B., Conneely, O.M., Edwards, D.P., and Carson, D.D. Progesterone receptor isoforms A and B differentially regulate MUC1 expression in uterine epithelial cells. Mol. Endocrinol., 20(10):2278-2291, 2006.

Yang, W., Gomes, R.R., Brown, A.J., Burdett, A.R., Alicknavitch, M., Farach-Carson, M.C., and Carson, D.D. Chondrogenic Differentiation of Perlecan Domain I, Collagen II, and Bone Morphogenetic Protein-2-Based Matrices. Tissue Eng., 12(7):2009-2024, 2006.

Liu, J.J., Huang, B.H., Zhang, J., and Carson, D.D. Repression of HIP/RPL29 expression induces differentiation in colon cancer cells. J. Cell Physiol., 207(2):287-292, 2006.

Gomes, R.R., Joshi, S.S., Farach-Carson, M.C., and Carson, D.D. Perlecan (Pln) secretion by C3H10T1/2 fibroblasts is required for BMP-2 and Pln Domain I supported chondrogenic differentiation. Differentiation, 74:53-63, 2006.

Savore, C., Zhang, C., Muir, C., Liu, R., Wyrwa, J., Shu, J., Zhau, H.E., Chung, L.W., Carson, D.D., and Farach-Carson, M.C. Perlecan knockdown in metastatic prostate cancer cells reduces heparin-binding growth factor responses in vitro and tumor growth in vivo. Clin. Exp. Metastasis, 22(5):377-390, 2005.

Yang, W.D., Gomes, R.R., Alicknavitch, M., Farach-Carson, M.C., and Carson, D.D. Perlecan domain I promotes FGF-2 delivery in collagen I fibril scaffolds. Tissue Engineering, 11:76-89, 2005.

Hecht J.T., Hayes, E., Haynes, R., Cole, W.G., Long, R.J., Farach-Carson, M.C., Carson, D.D. Differentiation-induced loss of heparan sulfate in human exostosis derived chondrocytes. Differentiation 73:212-221, 2005.

Carson, D.D. Uterine sensing of the embryo. Proc. Natl. Acad. Sci. U.S.A., 102:8397-8398, 2005.

Tang, M., Mikhailik, A., Pauli, I., Giudice, L.C., Fazelabas, A.T., Tulac, S., Carson, D.D., Kaufman, D.G., Barbier, C., Creemers, J.W., Tabibzadeh, S. Decidual differentiation of stromal cells promotes PC5/6 expression and lefty processing. Endocrinology, 146(12):5313-5320, 2005.

Farach-Carson, M.C., Hecht, J.T. and Carson, D.D. Heparan sulfate proteoglycans: key players in cartilage biology. Crit. Rev. Eukaryot. Gene Expr., 15:29-48, 2005.

Julian, J., Enders, A.C., Fazleabas, A.T. and Carson, D.D. Compartmental distinctions in uterine Muc-1 expression during early pregnancy in cynomolgous macaque (Macaca fascicularis) and baboon (Papio anubis). Hum. Reprod. 20:1493-1503, 2005.

Al-Shami R., Sorensen E.S., Ek-Rylander B., Andersson G., Carson D.D. and Farach-Carson MC. Phosphorylated osteopontin promotes migration of human choriocarcinoma cells via a p70 S6 kinase-dependent pathway. J. Cell Biochem. 94:1218-1233, 2005.

O'Connor, J.C., Julian, J., Lim S.D. and Carson, D.D. MUC1 expression in human prostate cancer cell lines and primary tumors. Prostate Cancer Prostatic. Dis., 8(1):36-44, 2004.

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