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Top blue bar image Department of Biochemistry & Cell Biology
 

Daniel Carson

The Schlumberger Chair of Advanced Studies and Research and Professor of Biochemistry and Cell Biology

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. The multifunctional cell surface mucin glycoprotein, MUC1, plays a key role in controlling access to the apical cell surface during the initial stage of implantation in all species studied to date. In addition, MUC1 is highly overexpressed by many epithelial tumors including those of the uterus, ovaries, breast and pancreas. In normal cells, MUC1 plays an antiadhesive role, lubricates epithelial cell surfaces and provides protection from microbial infection. Carson's Research In tumor cells, MUC1 protects from host immune surveillance and increases tumor cell resistance to chemotherapeutic agents. Most of these activities are attributable to the large, highly glycosylated MUC1 ectodomain. Recent studies indicate that the cytoplasmic tail of MUC participates in a diverse array in intracellular signal transduction events including protection from apoptosis and modulation of gene transcription. Cell surface expression of MUC1 includes local shedding of the MUC1 ectodomain as well as transitional control by various factors activated by steroid hormones, certain growth factors and cytokines. We are very interested in identifying the molecular controls over MUC1 gene and protein expression in both normal and tumor cell contexts. Stimulation of MUC1 is expected to improve barrier functions and increase protection against infection. Additionally, we are exploring therapeutic avenues to reduce MUC1 expression. Reduction of MUC1 in tumor cells is expected to enhance sensitivity of these tumors to killing by the host as well as chemotherapeutic agents. A second research area is pursued in close collaboration with Dr. Cindy Farach-Carson and involves the study of the heparan sulfate proteoglycan, perlecan, and enzymes that modify its structure in both the implantation process and in tumor cell contexts. Proteolytic enzymes and enzymes that modify the heparan sulfate polysaccharide chains of perlecan generate perlecan fragments with novel activities or modulate the growth factor binding activities, respectively. Mapping the changes that occur in the expression of these activities provides biological insight into the function of this proteoglycan which is expressed in species from C. elegans to humans. Moreover, generation of soluble perlecan fragments and/or modified heparan sulfate structures is proposed to be a useful marker of disease states in the utero-placental unit as well as certain cancers.

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Neto, E.P., Fuhrich, D.G., Carson, D.D., Engel, B.J. and Savaris, R.F. Elafin expression in mucosa of fallopian tubes is altered by hydrosalpinx.  Reprod. Sci. 2014

Dharmaraj, N., Chapela, P.J., Morgado, M., Hawkins, S.M., Lessey, B.A., Young, S.L. and Carson, D.D. Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis.  Hum. Reprod. 2014

Warren, C.R., Grindel, B., Francis, L., Carson, D.D. and Farach-Carson, M.C. Transcriptional Activation by NFκB Increases Perlecan/HSPG2 Expression in the Desmoplastic Prostate Tumor Microenvironment.  J. Cell. Biochem. 2014

Neeraja Dharmaraj, Engel BJ, Carson DD. Activated EGFR stimulates MUC1 expression in human uterine and pancreatic cancer cell lines.  J Cell Biochem., 114(10) 2013: 2314-22

Farach-Carson MC, Warren CR, Harrington DA, Carson DD. Border patrol: Insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue borders.  Matrix Biol. 2013

Lukianova-Hleb, E.Y., Ren, X., Constantinou, P.E., Danysh, B.P., Shenefelt, D.L., Carson, D.D., Farach-Carson, M.D., Kulchitsky, V.A., Wu,, X., Wagner, D.S., Lapotko, D.O. Improved cellular specificity of plasmonic nanobubbles versus nanoparticles in heterogeneous cell systems.  PLos One, 7(4) 2012: e34537

Danysh, B., Constantinou, P., Hleb, K., Lapotko, D. and Carson, D.D. The MUC1 ectodomain: A novel and efficient target for gold nanoparticle clustering and plasonic nanobubbles generation.  Theranostics, 2(8) 2012: 777-87

Zhang, C., Soori, M., Sikes, R.A., Carson, D.D., Chung, L.L.W., Farach-Carson, M.C. Paracrine factors produced by bone marrow stromal cells induce apoptosis and neuroendocrine differentiation in prostate cancer cells.  The Prostate , 71(2) 2011: 157-67

Constantinou, P., Danysh, B., Dharmaraj, N. and Carson, D.D. Transmembrane mucins as novel therapeutic targets.  Expert Rev. Endocrinol. Metab., 6(6) 2011, invited review: 835-849

Dharmaraj, N., Wang, P. and Carson, D.D. Cytokine and progesterone receptor interplay in the regulaton of MUC1 gene expression.  Mol. Endocrinol, 24 2010: 2253-2266

Wang, P., Dharmaraj, N., Brayman, M.J. and Carson, D.D. Peroxisome proliferator-activated receptor γ activation inhibits progesterone-stimulated human MUC1 expression.  Mol. Endocrinol, 24(7) 2010: 1368-1379

Dharmaraj, N., Gendler, S.J., and Carson, D.D. Expression of human MUC1 during early pregnancy in the human MUC1 transgenic mouse model.  Biol Reprod, 81 2009: 1182-1188

Julian, J., Dharmaraj, N., and Carson, D.D. MUC1 is a substrate for gamma secretase.  J Cell Biochem, 108 2009: 802-815

Kim-Saran, C., Farach-Carson, M.C., and Carson, D.D. Multifunctionality of extracellular and cell surface heparan sulfate proteoglycans.  Cell Mol Life Sci, 66 2009: 3421-3434

Pradhan, S., Zhang, C., Jia, X., Carson, D.D., Witt, R., and Farach-Carson, M.C. Perlecan domain IV peptide stimulates salivary gland cell assembly in vitro.  Tissue Eng Part A, 15 2009: 3309-3320

Farach-Carson MC, Brown AJ, Lynam M, Safran JB, Carson DD. A novel peptide sequence in perlecan domain IV supports cell adhesion and spreading.  Matrix Biology, 27 2008: 150-160

D’Souza SS, Fazleabas AT, Banerjee P, Sherwin RA, Sharkey, AM, 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 2008: 316-323

D’Souza, S., Yang, W., Marchetti, D. Muir, C., Farach-Carson, M.C. and Carson, DD. HIP/RPL29 antagonizes VEGF and FGF2 stimulated angiogenesis by interfering with HS-dependent responses.  J. Cell Biochem., 105(5) 2008: 1183-1193

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

Brown, A.J., Alicknavitch, M., D’Souza, S.S., Daikoku, T., Kirn-Safran, C.B., Marchetti, D., Carson D.D., and Farach-Carson, M.C. Heparanase expression and activity influences chondrogenic and osteogenic processes during endochondral bone formation.  Bone, 43(4) 2008:689-699: 689-699

Carson, D.D. Molecular and cell biology of embryo-uterine interactions: mammalian embryo implantation.  Semin. Cell Dev. Biol., 19(2) 2008: 160

Wang, P., Julian, J.A. 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 2008: 290-298

Carson, D.D. The cytoplasmic tail of MUC1: a very busy place.  Sci. Signal., 1(27) 2008: pe35

D'Souza SS, Daikoku T, Farach-Carson MC, Carson DD. Heparanase expression and function during early pregnancy in mice.  Biol. Reprod., 77 2007: 433-41

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., 21 2007: 2725-37

Farach-Carson MC, Carson DD. Perlecan--a multifunctional extracellular proteoglycan scaffold.  Glycobiology, 17 2007: 97-905

Brayman MJ, Julian J, 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, 20 2006: 2278-91

  • B.S. Biology (1975) University of Pennsylvania
  • Ph.D. Microbiology (1979) Temple University
  • Institute of Biosciences and Bioengineering
  • Expression and function of cell surface components that participate in and regulate cellular interactions in developing embryos and various tumor cell models. Study of the heparan sulfate proteoglycan, perlecan, and enzymes that modify its structure in both the implantation process and in tumor cell contexts.
Email: Daniel.D.Carson@rice.edu
Phone: 713-348-3347
Office: George R. Brown Hall , E100E