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Scholarly Interest Report
         
Daniel Douglas Carson
Professor
The Schlumberger Chair of Advanced Studies and Research and Professor of Biochemistry and Cell Biology
 
e-mail:Daniel.D.Carson@rice.edu
 
  • B.S. Biology (1975) University of Pennsylvania
  • Ph.D. Microbiology (1979) Temple University
 
Primary Department
   Department of BioSciences
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Department Affiliations
 
  • Institute of Biosciences and Bioengineering
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    Other Affiliations
     
  • MD Anderson
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    Research Areas
     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 reproductive tissues and in tumor cell contexts.
     
    Research Statement
     

    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.

     
    Selected Publications
     Refereed articles
     

    Chapela, P.J., Broaddus, R.R., Hawkins, S.M., Lessey, B.A. and Carson, D.D. "Cytokine stimulation of MUC4 expression in human female reproductive tissue carcinoma cell lines and endometrial cancer."  J. Cell. Biochem., 116 (2015) : 2649-5.

     
     

    Constantinou P.E., Morgado M. and Carson D.D. "Transmembrane Mucin Expression and Function in Embryo Implantation and Placentation." Adv. Anat. Embryol. Cell Biol., 216 (2015) : 51-68.

     
     

    Engel, B.J., Constantinou, P.E., Sablatura, L.K., Doty, N.J., Carson, D.D., Farach- Carson, M.C., Harrington, D.A. and Zarembinski T.I. "Multilayered, hyaluronic acidbased hydrogel formulations suitable for automated 3D high throughput drug screening of cancer-stromal cell cocultures." . Adv. Health Mater., 4 (2015) : 1664-74.

     
     

    Morgado, M., Sutton, M., Simmons, M., Warren, C.R., Lu, Z., Constantinou, P., Liu, J. and Carson D.D. "Tumor Necrosis Factor-α and Interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB." OncotargetIn Press

     
     

    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., 29(8) (2014) : 1730-8.

     
     

    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., 34 (2014) : 64-79.

     
     

    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., 21(3) (2014) : 401-7.

     
     

    Silva AL, Fuhrich DG, Carson DD, Engel BJ, Savaris RF "MUC1 expression in Fallopian tubes of women with hydrosalpinx."  Eur J Obstet Gynecol Reprod Biol., 180 (2014) : 106-10.


    doi: 10.1016/j.ejogrb.2014.06.001
     
     

    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., 115(7) (2014) : 1322-33.

     
     

    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.

     
     

    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.

     
     

    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.

     
     

    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.

     
     

    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.

     
     

    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.

     
     

    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.

     
     

    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.

     
     

    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.

     
     

    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.

     
     

    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.

     
     

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

     
     

    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.

     
     

    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.

     
     Articles
     

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

     
     

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

     
     Other
     

    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.

     
    Presentations
     Invited Talks
     

    "MUC1: Functions and Opportunities in Reproductive Medicine." Annual Research Day for the Center for the Study of Reproduction, McGill University, Montreal, Canada. (2011)

     
    Editorial Positions
     Associate Editor, Biology of Reproduction. (2011 - 2011)

     Associate Editor, Human Reproduction Update. (2010 - 2010)

     Associate Editor, Biology of Reproduction. (2010 - 2010)

     Member of the Editorial Board, Reproductive Biology and Endocrinology. (2011 - 2011)

     Member of the Editorial Board, Reproductive Biology and Endocrinology. (2002 - 2016)

     Member of the Editorial Board, International Journal of Medical Engineering and Informatics (IJMEI). (2007 - 2015)

     Member of the Editorial Board, Reproductive Biology and Endocrinology. (2010 - 2010)

     Associate Editor, Faculty of 1000 Medicine “Reproductive Endocrinology” Section. (2010 - 2010)

    Supervised Theses & Dissertations
     Curtis Warren, Ph.D. Evolution of the Perlecan/HSPG2 gene and Regulation of its Expression by Inflammatory Cytokines in Normal Tissue Models and Cancer. (2014) (Thesis Committee Member)

     Brian Engel, Ph.D. A two-pronged approach towards the development of novel therapeutics for advanced endometrial cancer. (2015) (Thesis Director)

     Yasmin Vasquez, Ph.D. FOXO1 Defines the Window of Receptivity for Embryo Implantation; Baylor College of Medicine. (2015) (Thesis Committee Member)

     Brian Grindel, Ph.D. Interplay of Perlecan and MMP-7/Matrilysin Regulates Metastatic Prostate Cancer Cell Behavior: Basic and Clinical Implications. (Thesis Committee Member)

    Awards, Prizes, & Fellowships
     Fellow, American Academy for the Advancement of Science (2012)

    Positions Held
     Adjunct Professor Biochemistry and Molecular Biology, UT MD Anderson Cancer Center. (2009 - 2014)

     Adjunct Professor of Biological Sciences, University of Delaware. (2009 - 2015)

     Adjunct Professor of Genetics, UT MD Anderson Cancer Center. (2015 - 2015)