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Scholarly Interest Report
         
Daniel Harrington
Faculty Fellow
Faculty Fellow in Biochemistry and Cell Biology
 
e-mail:Daniel.A.Harrington@rice.edu
 
  • Ph.D. Materials Science & Engineering (2004) Northwestern University, Evanston, IL
  • B.S. Materials Science & Engineering (1996) Northwestern University, Evanston, IL
 
Primary Department
   Department of BioSciences
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Department Affiliations
 
  • Department of BioSciences
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    Research Areas
     The design and application of next-generation biomaterials for tissue engineering and regenerative medicine: Salivary gland regeneration models, 3D prostate cancer metastasis models, Supramolecular systems for growth factor delivery
     

    Research Statement

     


    Current/Future Research Activities:


    3D prostate cancer metastasis models:  In an ongoing project through Cindy Farach-Carson’s group, we are developing hyaluronic acid (HA)-based hydrogel systems for 3D prostate cancer cell line culture, and for modeling their interaction with bone marrow stromal cell lines.  We are spearheading this effort among our colleagues and collaborators at the Texas Medical Center, in an effort to avoid the artifacts inherent in 2D cell culture.  Cell-substrate interactions dramatically affect cell phenotype, and we are focusing on removing the features of 2D culture (e.g. hard, flat surfaces; minimal cell-cell contacts; altered focal adhesion structure) that might yield inaccurate in vitro models of in vivo conditions. 


    Additionally, Dr. Farach-Carson’s group has found that particular patient-derived cell lines which would not proliferate in traditional 2D culture (and could only be passaged in vivo) are now amenable to growth in 3D HA networks.  We are examining the effects of mechanical properties and epitope concentration on cell behavior in these systems, as well as methods for identifying multiple cell types in a single culture, and tracking their behavior over time. These patient-derived cell lines have never been grown in vitro before, and we are combining them in multilayer hydrogel co-culture with bone-derived cells to derive more accurate models of metastasis.


    Salivary gland regeneration models: In another ongoing project through Cindy Farach-Carson’s laboratory, we are investigating materials and methods for salivary gland regeneration, using crosslinkable HA polymers as a base scaffold. These systems are being investigated as a possible therapeutic for the tissue damage that results from radiation therapy used in treating oral cancers.  Primary human tissues are acquired prior to radiotherapy, and individual cell lineages are separated and cultured for later reassembly in the neotissue. Epitopes derived from perlecan (Pln) are being selectively incorporated into the HA network structure to promote lumen formation and microscale growth factor depots (also made from tightly crosslinked HA) are added to promote branching morphogenesis and migration. We additionally incorporate peptidic sequences that enable cell adhesion and migration through these hydrogels.


    High-Throughput Screening for anti-cancer drugs: In collaboration with industry partners, and with Drs. Dan Carson and Pam Constantinou, we are developing multiayered co-cultures of cancer, stroma, and other related cells in miniaturized multiwell plates, suitable for robotic screening of libraries of chemotherapeutics. These systems benefit from a true 3D environment and communication among the cell layers. Our early efforts demonstrate a closer correlation to clinical trial results for our 3D systems than for the traditional test method of cells plated on 2D plastic. We continue to improve this method by incorporating other features (cells, matrix, perfusion) present in the tumor microenvironment.


    Supramolecular systems for growth factor delivery: As part of a collaboration with Dr. Carol Podlasek at Northwestern University, we are examining self-assembling peptide amphiphile (PA) hydrogels for the treatment of erectile dysfunction (ED) after radical prostatectomy (RP). Injury to the cavernous nerve or other surrounding peripheral nerves in the penis is a known complication of RP, and Sonic Hedgehog (Shh) protein is known to be involved in the maintenance – or malfunction – of penile smooth muscle function after RP.  Shh signaling prevents smooth muscle apoptosis, and preserves penile function.  We are using PA gels, loaded with Shh protein, as a delivery system within the penile smooth muscle, to help prevent ED in a rodent nerve crush model.  Similarly, we are examining the use of “noodle” PAs, with greater mechanical integrity for surgical placement, as Shh delivery depots for cavernous nerve maintenance and/or regeneration.  We have already observed significant improvements in nerve preservation and retention of physiological function due to Shh-PA.  These studies have implications in ED treatment, both after RP and for diabetic-induced ED.

     
    Teaching Areas
     Biomaterials
     
    Selected Publications
     Abstracts
     

    Fong ELS, Martinez M, Yang J, Chung, LMK, Mikos AG, Navone NM, Harrington DA, Farach-Carson MC "Culturing patient-derived prostate cancer xenografts using a three-dimensional hydrogel system for drug testing and mechanistic studies." Cancer Research, 74: 2030.

     
     Refereed articles
     

    Fong ELS, Wang X, Yang J, Morgado M, Mikos AG, Harrington DA, Navone NM, Farach-Carson MC. A 3D in vitro model of patient-derived prostate cancer xenograft for controlled interrogation of in vivo tumor-stromal interactions. Biomaterials.  (2016) 77:164-172

     
     

    Engel BJ, Constantinou PE, Sablatura LK, Doty NJ, Carson DD, Farach-Carson MC, Harrington DA, Zarembinski TI. Multilayered, Hyaluronic Acid-Based Hydrogel Formulations Suitable for Automated 3D High Throughput Drug Screening of Cancer-Stromal Cell Cocultures. Adv Healthc Mater. (2015) 4(11):1664-74

     
     

    Pan T, Fong EL, Martinez M, Harrington DA, Lin SH, Farach-Carson MC, Satcher RL. Three-dimensional (3D) culture of bone-derived human 786-O renal cell carcinoma retains relevant clinical characteristics of bone metastases.  Cancer Letters (2015) 365: 89-95.

     
     

    Fong ELS, Martinez M, Yang J, Mikos AG, Navone NM, Harrington DA, Farach-Carson MC "Hydrogel-Based 3D Model of Patient-Derived Prostate Xenograft Tumors Suitable for Drug Screening." Molecular Pharmaceutics, 11(7) (2014) : 2040-50.

     
     

    Pradhan-Bhatt S, Harrington DA, Duncan RL, Farach-Carson MC, Jia X, Witt RL "A novel in vivo model for evaluating functional restoration of a tissue-engineered salivary gland." Laryngoscope, 124(2) (2014) : 456-61.


    doi: 10.1002/lary.24297
     
     

    Xu X, Sabanayagam CR, Harrington DA, Farach-Carson MC, Jia X "A Hydrogel-Based Tumor Model for the Evaluation of Nanoparticle-Based Cancer Therapeutics." Biomaterials, 35(10) (2014) : 3319-3330.

     
     

    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 (2013) : 64-79.


    doi: 10.1016/j.matbio.2013.08.004
     
     

    Pradhan-Bhatt S, Harrington DA, Duncan RL, Jia X, Witt RL, Farach-Carson MC ". Implantable three-dimensional salivary spheroid assemblies demonstrate fluid and protein secretory responses to neurotransmitters ." Tissue Eng Part A, 19 (2013) : 1610-20.


    doi: 10.1089/ten.TEA.2012.0301
     
     

    Angeloni, NL; Bond, CW; Harrington, DA; Stupp, SI; Podlasek, CA "Sonic hedgehog is Neuroprotective in the Cavernous Nerve with Crush Injury." Journal of Sexual Medicine (2012) In Press

     
     

    Bond, CW; Angeloni, NL; Harrington, DA; Stupp, SI; Podlasek, CA "Sonic Hedgehog Regulates Brain Derived Neurotrophic Factor in Normal and Regenerating Cavernous Nerves." Journal of Sexual Medicine (2012) In Press

     
     

    Xu, X; Gurski, LA; Zhang, C; Harrington, DA; Farach-Carson, MC; Jia, X "Recreating the Tumor Microenvironment in a Bilayer, Hyaluronic Acid Hydrogel Construct for the Growth of Prostate Cancer Spheroids." Biomaterials, 33(35) (2012) : 9049-9060.

     
     

    Angeloni, NL; Bond, CW; Tang, Y; Harrington, DA; Zhang, S; Stupp, SI; McKenna, KE; Podlasek, CA "Regeneration of the Cavernous Nerve Using Aligned Peptide Amphiphile Nanofibers." Biomaterials, 32(4) (2011) : 1091-101.

     
     

    Mishra, R; Vijayan, KV; Coletti, EC; Harrington, DA; Matthiesen, T; Goh, SK; Wold, LE; Backer,CA; Kaushal, S "Characterization and Functionality of Cardiac Progenitor Cells in Congenital Heart Patients." Circulation, 123(4) (2011) : 364-73.

     
     

    Xu, X; Jha, AK; Harrington, DA; Farach-Carson, MC; Jia, X "Hyaluronic Acid-Based Hydrogels: from a Natural Polysaccharide to Complex Networks." Soft Matter, 8(12) (2012) : 3280-3294.

     
     

    Angeloni, NL; Bond, CW; Tang, Y; Harrington, DA; Zhang, S; Stupp, SI; McKenna, KE; Podlasek, CA "Regeneration of the Cavernous Nerve Using Aligned Peptide Amphiphile Nanofibers." Biomaterials (2010) In Press

     
     

    Bond, CW; Angeloni, NL; Harrington, DA; Stupp, SI; McKenna, KE; Podlasek, CA "Peptide Amphiphile Nanofiber Delivery of Sonic Hedgehog Protein to Reduce Smooth Muscle Apoptosis in the Penis After Cavernous Nerve Resection." J Sexual Med (2010) In Press

     
     

    MacIver, RH; Stewart, RD; Backer, CL; Tsao, S; Harrington DA; Mavroudis, CM "An improved in vivo method for atrioventricular node ablation via thoracotomy." Braz J Med Biol Res, 43(2) (2010) : 206-10.

     
     

    Mishra, R; Vijayan, KV; Coletti, EC; Harrington, DA; Matthiesen, T; Goh, SK; Wold, LE; Backer,CA; Kaushal, S "Characterization and Functionality of Cardiac Progenitor Cells in Congenital Heart Patients." Circulation (2010) In Press

     
     Book chapters
     

    Harrington DA, Martinez M, Wu D, Pradhan-Bhatt S, Farach-Carson MC "Salivary Gland Tissue Engineering and Future Diagnostics." Salivary Diagnostics (2014) In Press

     
     

    Pradhan-Bhatt, S; Cannon, K; Zakheim, D; Harrington, DA; Duncan, RL; Jia, X; Farach-Carson, MC; Witt, RL; “Salivary Gland Tissue Engineering and Repair” in Stem Cell Biology and Tissue Engineering in Dental Sciences, ed. Vishwakarma A; Sharpe, P; Shi, S; Ramalingham, M; 2014, Elsevier.

     
     

    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 "HyStemŽ, a Customizable Hyaluronan-Based Hydrogel Matrix for 3D Cell Culture." 3D Cell Culture: Technology and Application (2014) In Press

     
    Presentations
     Invited Talks
     

    "Salivary Acinar Cell Responses to Integrin Ligands in HA Hydrogels." Gulf Coast Undergraduate Research Symposium (GCURS), (Oct, 2014) With Kothari, R; Farach-Carson, MC

     
     

    "Crossing the Bridge." BRC Ideas That Go Viral, BIOE Seminar Series, (8/6/2013)

     
     

    "Cavernous Nerve Regeneration Using Sonic Hedgehog Nanofibers." Tissue Engineering & Regenerative Medicine International Society (TERMIS), (December 2011) With Angeloni, NL; Bond, CW; Tang, Y; Zhang, S; Stupp, SI; McKenna, KE; Podlasek, CA

     
     

    "Covalent Tethering of Perlecan Epitopes via ‘Click’ Chemistry." Tissue Engineering & Regenerative Medicine International Society (TERMIS), (December 2011) With Ruiz, JL; Cortez, A; Farach-Carson, MC

     
     

    "Engineering an Artificial Salivary Gland." Tissue Engineering & Regenerative Medicine International Society (TERMIS), (December 2011) With Pradhan-Bhatt, S; Duncan, RL; Witt, RL; Jia, X; Farach-Carson, MC

     
     

    "Isolation and Functionality of Cardiac Progenitor Cells in Congenital Heart Patients." American Heart Association 2010 Conference, (2010) With R. Mishra, et al

     
     

    "Peptide Amphiphile Nanofiber Delivery of Sonic Hedgehog Protein to Reduce Smooth Muscle Apoptosis in the Penis After Cavernous Nerve Resection." SMSNA 2010, (2010) With C. Bond, et al

     
     Lectures
     

    "Developing a Clinically Relevant In Vitro Model of Bone Metastatic Prostate Cancer." TERMIS-AM, Atlanta, GA. (11/13/2013) With Fong, ELS; Mikos, AG; Farach-Carson, MC

     
     

    "Sonic hedgehog Regulation of BDNF in the Cavernous Nerve." American Urological Association, (May, 2012) With Bond, CW; Angeloni, NL; Stupp, SI; Podlasek, CA

     
     Posters
     

    "Context-Specific Salivary Acinar Cell Responses to Integrin Ligands in HA Hydrogels." Rice Summer Research Institute, (Aug, 2014) With Kothari, RS; Martinez, M; Fong, ELS; Farach-Carson, MC

     
     

    "Coordinated Cellular interplay in 3D Reorganization of Human Parotid Salivary Gland Cells." Biomedical Engineering Society (BMES), San Antonio. (Oct, 2014) With Wu, D.; Pradhan-Bhatt, S.; Harrington, D. A.; Witt, R. L.; Farach-Carson, M. C.

     
     

    "Culturing Patient-Derived Prostate Cancer Xenografts Using a 3D Hydrogel System for Drug Testing and Mechanistic Studies." American Association of Cancer Research (AACR), San Diego, CA. (Apr, 2014) With Fong, ELS; Martinez, M; Yang, J; Chung, LMK; Mikos, AG; Navone, NM; Harrington, DA; Farach-Carson, MC

     
     

    "Effective Orifice Area Analysis of a Stent-Mounted Pediatric Heart Valve." Rice Undergraduate Research Symposium (RURS), (Apr, 2014) With Radia, N; Chun, K; Justino, H

     
     

    "Engineering an Ex Vivo Analogue of Bone Marrow to Model Bone Metastasis." American Society for Bone and Mineral Research (ASBMR), Houston, TX. (Sep, 2014) With Fong, ELS; Yang, J; Jia, X; Mikos, AG; Navone, NM; Farach-Carson, MC

     
     

    "Engineering the Bone Metastatic Prostate Cancer Microenvironment Using a Three-Dimensional Hyaluronan-Based Hydrogel System." Tissue Engineering and Regenerative Medicine International Society (TERMIS), Washington, DC. (Dec, 2014) With Fong, ELS; Harrington, DA; Mikos, AG; Farach-Carson, MC

     
     

    "Functional Evaluation of an Adjustable Pediatric Stent-Mounted Heart Valve." Rice Undergraduate Research Symposium (RURS) - First Place, (Apr, 2014) With Clark, G; Chun, K; Justino, H

     
     

    "Isolation, Characterization, and Functional Analysis of Human Salivary Gland Myoepithelial Cells for Use in Tissue Regeneration." Tissue Engineering and Regenerative Medicine International Society (TERMIS), Washington, DC. (Dec, 2014) With Zakheim, DR; Ogzdemir, T; Chapela, PJ; Cannon, KS; Duncan, RL; Farach-Carson, MC; Jia, X; Witt, RL; Pradhan Bhatt, S

     
     

    "Culture of Human Salivary Gland Cells in Hyaluronic Acid (HA)-Based Hydrogels for Use in Tissue Engineering." TERMIS-AM, Atlanta, GA. (11/10/2013) With Pradhan Bhatt, S; Xu, X; Fong, ELS; Jia, X; Witt, RL; Farach-Carson, MC

     
     

    "Developing a Clinically Relevant In Vitro Model of Bone Metastatic Prostate Cancer." Advances in Tissue Engineering, Houston, TX. (8/17/2013) With Martinez, M; Fong, ELS; Mikos, AG; Yang, J; Navone, NM; Farach-Carson, MC

     
     

    "Development of a Three-Dimensional In Vitro Co-Culture Model of Bone Metastatic Prostate Cancer." American Society for Bone and Mineral Research (ASBMR), Baltimore, MD. (10/5/2013) With Fong, ELS; Yau, OK; Martinez, M; Yang, J; Jia, X; Mikos, AG; Navone, NM; Farach-Carson, MC

     
     

    "Development of an in vitro Co-Culture Model of Bone Metastatic Prostate Cancer." Advances in Tissue Engineering, Houston, TX. (8/17/2013) With Yau, OK; Fong, ELS; Mikos, AG; Farach-Carson, MC

     
     

    "Functional Assembly of Salivary Glands to Relieve Xerostomia." Gordon Research Conference: Salivary Glands & Exocrine Biology, Galveston, TX. (2/4/2013) With Pradhan Bhatt, S; Duncan, RL; Jia, X; Witt, RL; Farach-Carson, MC

     
     

    "Gelatin Addition in a 3D Hyaluronan Hydrogel: Effects on Growth, Morphology and Phenotype of a Patient-Derived Bone Metastatic Prostate Cancer Xenograft." Advances in Tissue Engineering, Houston, TX. (8/17/2013) With Berger, SN; Fong, ELS; Martinez, M; Navone, NM; Farach-Carson, MC

     
     

    "Bone Morphogenetic Protein  (BMP-2) from Perlecan Domain I-Functionalized Electrospun Poly(caprolactone) (PCL) Scaffolds to Promote Osteogenic Differentiation of Mesenchymal Stem Cells (MSCs)." Advances in Tissue Engineering, (Aug, 2012) With Chiu, Y-C; Grindel, BJ; Kasper, KF; Farach-Carson, MC; Mikos, AG

     
     

    "Effects of Crosslinking Architecture of Hyaluronic Acid Hydrogels on Aggregate Morphology of Prostate Cancer Cell Line." Advances in Tissue Engineering, (Aug, 2012) With Augello, C; Fong, E; Zarembinski, TI; Jia, X; Delk, NA; Farach-Carson, MC

     
     

    "Engineering an Artificial Salivary Gland." American Head and Neck Society, (Jul, 2012) With Pradhan-Bhatt, S; Xian, X; Kirschner, K; Duncan, RL; Farach-Carson, MC; Jia, X; Witt, RL

     
     

    "Functional Salivary Gland Restoration Using Expanded Populations of Human Salivary Progenitor Cells." International Association for Dental Research, (Jun, 2012) With Pradhan-Bhatt, S; Duncan, RL; Jia, X; Witt, RL; Farach-Carson, MC

     
     

    "Models and Mechanisms for Pediatric Pulmonary Valve Replacement." Rice Summer Research Institute, (Aug, 2012) With Organ, R; Chun, K; Grande-Allen, KJ; Justino, H

     
     

    "Sonic hedgehog Signaling in Crushed and Regenerating Cavernous Nerve." American Urological Association, (May, 2012) With Angeloni, NL; Bond, CW; Stupp, SI; Podlasek, CA

     
     

    "Peptide Amphiphile Nanofiber Delivery of Sonic Hedgehog Protein to Reduce Smooth Muscle Apoptosis in the Penis After Cavernous Nerve Resection." American Urological Society, (May 2011) With Bond, CW; Angeloni, NL; Stupp, SI; McKenna, KE; Podlasek, CA

     
    Supervised Theses & Dissertations
     Liezl Balaoing, PhD Evaluation of Valvular Endothelial Cell Hemostatic Behavior in Native Valves and Novel Co-Culture Methods. (2014) (Thesis Committee Member)

     Joao Paolo Mattos Almeida, PhD Gold Nanoparticle Platforms for Antigen and Adjuvant Delivery in Cancer Immunotherapy. (2014) (Thesis Committee Member)

     Mariane Martinez, PhD Role of cell-extracellular matrix (ECM) interactions on tissue morphology, cell phenotype and organization in a salivary gland regeneration model. (2017) (Thesis Director)

     Lindsey Sablatura, PhD TBD. (Thesis Committee Member)

     Steven Higbee, PhD Engineering Vascularized Hepatic Tissue in Bioactive Poly(ethylene glycol)-based Hydrogels. (Thesis Committee Member)

     Yang Gao, PhD Evaluating Efficiency and Maturation of Cardiomyocytes Derived from Amniotic Fluid-Derived Stem Cells and Cardiac Progenitor Cells for Use in a Tissue Engineered Cardiac Patch. (Thesis Committee Member)

     Thomas Clements, PhD Homologous Recombination (HR) based genome editing using the CRISPR-Cas mechanism in zebrafish. (Thesis Committee Member)

     Enrique Martinez, PhD Atlastin-dependent ER integrity influences de novo peroxisome biogenesis. (Thesis Committee Member)

     Kelsea Hubka, PhD Perlecan Domain I Gradients in Hyaluronic Acid Hydrogels for Spatially-Defined Growth Factor Gradients for Tissue Engineering . (Thesis Committee Member)

     Matthew Sapp, PhD Evaluation of the Role of Extracellular Matrix and Hypoxia in Aortic Valve Calcification and Mitral Valve Disease. (Thesis Committee Member)

     Christopher Alex Arevalos, PhD Modulating Neoangiogenesis of Heart Valve Cells Utilizing Natural and Synthetic Biomimetic Scaffolds: A Platform for Better Understanding Pathological Angiogenesis in CAVD and for Augmentation of Pediatric Tissue Engineered Heart Valves. (Thesis Committee Member)

     Brandi Scully, MS In Vivo and In Vitro Remodeling of a Small Intestinal Submucosa Extracellular Matrix Cardiac Patch in an Ovine Model and Splashing Bioreactor. (Thesis Committee Member)

     Daniel Puperi, PhD Bioinspired Trilayered Scaffolds for Aortic Valve Tissue Engineering. (Thesis Committee Member)

    Positions Held
     Lecturer, Rice University, Bioengineering. (2012 - 2012)

     Assistant Director, Collaborative Research Laboratory (CRL) . (2010 - 2010)