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Scholarly Interest Report
         
Pamela E. Constantinou Papadopoulos
Faculty Fellow
Faculty Fellow in Biochemistry and Cell Biology
 
e-mail:pamela.constantinou@rice.edu
 
  • Ph.D. Chemistry (2005) New York University, New York, NY
  • B.A. Chemistry (1999) Vassar College, Poughkeepsie, NY
 
Primary Department
   Department of BioSciences
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Department Affiliations
 
  • Department of BioSciences
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    Research Areas
     Transmembrane mucins as targets for cancer therapies; 3D models for epithelial cancers for high throughput drug screening
     

    Research Statement:

     

     



    In healthy epithelial cells, transmembrane mucins are expressed on the apical surface of cells and are responsible for protecting cells from microbial and enzymatic attack. These highly glycosylated proteins contain ectodomains that can extend several hundreds of nanometers from the cell surface, providing a well-hydrated physical barrier to the cell. However, the loss of normal topology and polarity in cancer cells results in aberrant mucin expression over the entire cell surface. Overexpression, altered glycosylation patterns, and mRNA splice variants are all hallmarks of mucins in cancer cells and are commonly used as biomarkers for cancer progression. Our current projects exploit these differences in mucins as targets for cancer therapies.


    Additionally, our laboratory has been investigating the use of three-dimensional (3D) culture models for better clinical predictability of drugs in patient trials.  We have incorporated hydrogels into high throughput drug screening platforms for cancer cells co-cultured with stromal cells.  Cells grown in our 3D system better recapitulate the clinical outcome of drug efficacy of cancer patients than cells grown using conventional tissue culture on plastic.  In our efforts to maintain in vivo tumor heterogeneity, we are currently integrating patient derived xenografts in our 3D models.

     
    Selected Publications
     Refereed articles
     

    M. Morgado, M.N. Sutton, M. Simmons, C.R. Warren, Z. Lu, P.E. Constantinou, J. Liu, L. Francis, R.S. Conlan, R.C. Bast, D.D. Carson "Tumor Necrosis Factor-α and Interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB." Oncotarget, 7 (2016) : 14871.

     
     

    B.J. Engel,* P.E. Constantinou,*+ L.K. Sablatura, N.J. Doty, D.D. Carson, M.C. Farach-Carson, D.A. Harrington, T.I. Zarembinski "Multi-Layered, Hyaluronic Acid-Based Hydrogel Formulations Suitable for Automated 3D High Throughput Drug Screening of Cancer-Stromal Cell Co-Cultures." Adv Healthc Mater, 4 (2015) : 1664-74.

     
     

    Rogers, A., Constantinou, P.E., Jamison, D.K., Driver, J.W., Diehl, M.R. "Construction and analyses of elastically coupled multiple-motor systems." Methods Enzymol, 540 (2014) : 189-204.

     
     

    Lukianova-Hleb EY, Campbell KM, Constantinou PE, Braam J, Olson JS, Ware RE, Sullivan DJ Jr, Lapotko DO. "Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria." Proc Natl Acad Sci USA, 111(3) (2014) : 900-5.In Press

     
     

    B.P. Danysh,* P.E. Constantinou,* E.Y. Lukianova-Hleb,* D.O. Lapotko, D.D. Carson "The MUC1 ectodomain: A novel and efficient target for gold nanoparticle clustering and vapor nanobubble generation.." Theranostics, 2(8) (2012) : 777-787.

     
     

    E.Y. Lukianova-Hleb, X., Ren, P.E. Constantinou, B.P. Danysh, D.L. Shenefelt, D.D. Carson, M. C. Farach-Carson, V. A. Kulchitsky, X. Wu, D. S. Wagner, D. O. Lapotko "Improved Cellular Specificity of Plasmonic Nanobubbles versus Nanoparticles in Heterogeneous Cell Systems." PLOS One, 7(4) (2012) : e34537.

     
     

    N. Nguyen, J.J. Birktoft, R. Sha, T. Wang, J. Zheng, P.E. Constantinou, S.L. Ginell, Y. Chen, C. Mao, N.C. Seeman "The Absence of Tertiary Interactions in a Self-Assembled DNA Crystal Structure." J. Mol. Recognit, 25 (2012) : 234-237.

     
     

    P. E. Constantinou, B. P. Danysh, N. Dharmaraj, D. D. Carson "Transmembrane mucins as novel therapeutic targets." Exper Rev. Endocrinol Metab, 6 (2011) : 835-949.

     
     

    D. K. Jamison, J. Driver, A. R. Rogers, P. E. Constantinou, M. R. Diehl "Two Kinesins Transport Cargo Primarily via the Action of One Motor: Implications for Intracellular Transport." Biophys. J., 99 (2010) : 2967-77.

     
     

    P. E. Constantinou and M. R. Diehl "The Mechanochemistry of Integrated Motor Protein Complexes." J. Biomech., 43 (2010) : 31-37.

     
     

    J. P. Zheng, J. J. Birktoft, Y. Chen, T. Wang, R. Sha, P. E. Constantinou, S. L. Ginnell, C. Mao, N. C. Seeman "From Molecular to Macroscopic via the Rational Design of a Self-assembled 3D DNA crystal." Nature, 461 (2009) : 74-77.

     
     Book chapters
     

    Zarembinski TI, Engel BJ, Doty NJ, Constantinou PE, Onorato MV, Erickson IE, Fong ELS, Martinez M, Milton RL, Danysh BP, Delk NA, Harrington DA, Farach-Carson MC, Carson DD "HyStem®, a Customizable Hyaluronan-Based Hydrogel Matrix for 3D Cell Culture." 3D Cell Culture: Technology and Application In Press

     
     

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

     
     

    N.C. Seeman, J.J. Birktoft, R. Sha, H. Gu, T. Wang, J. Zheng, J. Chao, P. Constantinou, B. Ding, C. Mao, “DNA Crystals, Constructs, and Devices.” Handbook of Nanoscience, Engineering, and Technology, Third Edition, 1037-1050 (2012).

     
     Conference papers
     

    N. Whiting, J. Hu, P. Constantinou, N.Z. Millward, J. Bankson, D. Gorenstein, A. Sood, D. Carson, P. Bhattacharya "Developing hyperpolarized silicon particles for advanced biomedical imaging applications." Proc. SPIE 9417; Medical Imaging 2015: Biomedical Applications in Molecular, Structural, and Functional Imaging Technologies, Devices and Applications , 941702 (2015)

     
    Presentations
     Invited Talks
     

    "A Hyaluronic Acid-Based Hydrogel System for 3D High Throughput Drug Screening,High-Content Analysis & 3D Screening Conference, Cambridge Healthtech Institute, Boston, MA." (November 2016)

     
     

    "Utilizing tools from glycobiology for improved cancer diagnostic and treatments, Department of Biological Sciences, The University of Texas at Dallas." (February 4, 2016)

     
     

    "Multi-Layered, Hyaluronic Acid-Based Hydrogel System for Automated 3D High Throughput Drug Screening of Cancer-Stromal Cell Co-Cultures." The Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School. (June 2015)

     
     

    "Targeting Membrane Bound Mucins in Pancreatic Cancer." University of Texas Medical Branch Mini-symposium on Pancreatic Disease, Galveston, TX. (January 2012) With N. Dharmaraj, D. D. Carson

     
     

    "Targeting Membrane Bound Mucins in Pancreatic Cancer." Elkins Pancreas Center Retreat, Baylor College of Medicine, Houston, Texas. (November 2012)

     
     Lectures
     

    "Nanotechnology and Cancer, BIOC 460/560, Rice University, Houston, TX."

     
     

    Nanotechnology and Cancer, BIOC 460/560, Rice University, Houston, TX

     
     

    Nanotechnology and Cancer, BIOC 460/560, Rice University, Houston, TX

     
     

    "Nanotechnology and Cancer." BIOC 460/560, Cancer Biology, Rice University , Houston, TX. (April 2013)

     
     

    "Nanotechnology and Cancer BIOC 460, 560, Cancer Biology." (April 2012)

     
     Posters
     

    "Multi-Layered, Hyaluronic Acid-Based Hydrogel System for Automated 3D High Throughput Drug Screening of Cancer-Stromal Cell Co-Cultures.” American Association for Cancer Research (AACR), New Orleans." (April 2016)

     
     

    "Molecular Imaging of Mucin-Expressing Colon Tumors Using Targeted Hyperpolarized Silicon Nanoparticles." CPRIT Innovations Conference, Austin, TX. (November 2015) With Julie X. Liu, Jingzhe Hu, Nicholas Whiting, Jennifer S. Davis, Niki Zacharias Millward, David G. Menter, Pratip K. Bhattacharya, Daniel D. Carson

     
     

    "Multi-Layered, Hyaluronic Acid-Based Hydrogel System for Automated 3D High Throughput Drug Screening of Cancer-Stromal Cell Co-Cultures." World Preclinical Conference, Boston, MA. (June 2015) With B.J. Engel, L.K. Sablatura, N.J. Doty, D.D. Carson, M.C. Farach-Carson, D.A. Harrington, T.I. Zarembinski

     
     

    "MUC1 Targeted Nanoparticle Delivery and Cytolysis." American Association for Cancer Research, Special Conference in Nano in Cancer, Miami, FL. (January 2011) With B. P. Danysh, E. Y. Lukianova-Hleb, D. O. Lapotko, D. D. Carson

     
     

    "MUC1-Targeted Plasmonic Nanobubble Theranostics for Pancreatic Cancer." NCI Alliance for Nanotechnology Annual Principal Investigators’ Meeting, Boston, MA. (September 2011) With B. P. Danysh, E. Y, Lukianova-Hleb, D. O. Lapotko, D. D. Carson

     
    Supervised Theses & Dissertations
     Julie Liu, Ph.D. Targeting and Interrogating Biological Role of MUC1 in Colorectal Cancer . (2019) (Thesis Director)

    Awards, Prizes, & Fellowships
     Career Enhancement Award 2016, MD Anderson SPORE in Uterine Cancer

     Career Development Award 2014-15, MD Anderson SPORE in Uterine Cancer

     Career Development Award 2014-15, MD Anderson SPORE in Uterine Cancer

     IBB Medical Innovation Award, Institute of Biosciences and Bioengineering (2013)

    Positions Held
     Scientific Advisor, MIMETAS, Inc. (2016 - 2016)