Human Models for Analysis of Pathways (H-MAPs) Center

EPA Grant Number: R835737
Center: Human Models for Analysis of Pathways (H–MAPs) Center
Center Director: Murphy, William L
Title: Human Models for Analysis of Pathways (H-MAPs) Center
Investigators: Murphy, William L , Ashton, Randolph S , Beebe, David , McIntosh, Brian , Roy, Sushmita , Sheibani, Nader , Thomson, James , Vickerman-Kelley, Vernella
Current Investigators: Murphy, William L , Ashton, Randolph S , Beebe, David , Daly, William , McIntosh, Brian , Roy, Sushmita , Sheibani, Nader , Thomson, James
Institution: University of Wisconsin - Madison
EPA Project Officer: Klieforth, Barbara I
Project Period: December 1, 2014 through November 30, 2018
Project Amount: $5,999,600
RFA: Organotypic Culture Models for Predictive Toxicology Center (2013) RFA Text |  Recipients Lists
Research Category: Human Health , Health , Safer Chemicals

Objective:

The need for human, organotypic culture models coupled with the requirements of contemporary toxin screening (i.e. reproducibility, high throughput, transferability of data, clear mechanisms of action, defined adverse outcomes) frame an opportunity for a paradigm shift. We propose to establish the Human Models for Analysis of Pathways (H-MAPs) Center to advance the next generation of toxicity testing formats, and to develop a broadly applicable set of tools for toxin screening.

The H-MAPs Center Objectives are to:

  • Generate pluripotent stem cell-derived cells that properly represent the diverse phenotypic characteristics of developing or mature human somatic cells;
  • Generate organotypic cell culture models that are robust and reproducible;
  • Translate organotypic cell culture models to microscale systems for HTS;
  • Combine genomic/epigenomic analyses with bioinformatics to gain molecular level insights into organotypic model assembly and the pathways influenced by toxins.

The H-MAPs Center will bring together leading experts in human pluripotent stem cell biology, human development, and microscale tissue engineering to develop organotypic human models. The Center will also form organotypic human models in robust, innovative high throughput screening systems and identify mechanisms of action associated with toxicity using bioinformatics-based pathway analysis.


Journal Articles: 53 Displayed | Download in RIS Format

Other center views: All 183 publications 53 publications in selected types All 53 journal articles
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Journal Article Aboualizadeh E, Ranji M, Sorenson CM, Sepehr R, Sheibani N, Hirschmugl CJ. Retinal oxidative stress at the onset of diabetes determined by synchrotron FTIR widefield imaging: towards diabetes pathogenesis. Analyst 2017;142(7):1061-1072. R835737 (2017)
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  • Journal Article Aboualizadeh E, Sorenson CM, Schofield AJ, Unger M, Sheibani N, Hirschmugl CJ. Temporal diabetes-induced biochemical changes in distinctive layers of mouse retina. Scientific Reports 2018;8(1):1096. R835737 (2017)
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  • Journal Article Barry C, Schmitz MT, Propson NE, Hou Z, Zhang J, Nguyen BK, Bolin JM, Jiang P, McIntosh BE, Probasco MD, Swanson S, Stewart R, Thomson JA, Schwartz MP, Murphy WL. Uniform neural tissue models produced on synthetic hydrogels using standard culture techniques. Experimental Biology and Medicine 2017;242(17):1679-1689. R835737 (2017)
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  • Journal Article Belair DG, Schwartz MP, Knudsen T, Murphy WL. Human iPSC-derived endothelial cell sprouting assay in synthetic hydogel arrays. Acta Biomaterialia 2016;39:12-24. R835737 (2016)
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  • Journal Article Belair DG, Miller MJ, Wang S, Darjatmoko SR, Binder BY, Sheibani N, Murphy WL. Differential regulation of angiogenesis using degradable VEGF-binding microspheres. Biomaterials 2016;93:27-37. R835737 (2015)
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  • Journal Article Belair DG, Le NN, Murphy WL. Regulating VEGF signaling in platelet concentrates via specific VEGF sequestering. Biomaterials Science 2016;4(5):819-825. R835737 (2015)
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  • Journal Article Chasman D, Walters KB, Lopes TJ, Eisfeld AJ, Kawaoka Y, Roy S. Integrating transcriptomic and proteomic data using predictive regulatory network models of host response to pathogens. PLoS Computational Biology 2016;12(7):e1005013. R835737 (2015)
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  • Journal Article Chasman D, Siahpirani A, Roy S. Network-based approaches for analysis of complex biological systems. Current Opinion in Biotechnology 2016;39:157-166. R835737 (2015)
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  • Journal Article Chasman D, Roy S. Inference of cell type specific regulatory networks on mammalian lineages. Current Opinion in Systems Biology 2017;2:130-139. R835737 (2017)
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  • Journal Article Dinu D, Chu C, Veith A, Lingappan K, Couroucli X, Jefcoate CR, Sheibani N, Moorthy B. Mechanistic role of cytochrome P450 (CYP)1B1 in oxygen-mediated toxicity in pulmonary cells: a novel target for prevention of hyperoxic lung injury. Biochemical and Biophysical Research Communications 2016;476(4):346-351. R835737 (2016)
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  • Journal Article Falero-Perez J, Park S, Sorenson CM, Sheibani N. PEDF expression affects retinal endothelial cell proangiogenic properties through alterations in cell adhesive mechanisms. American Journal of Physiology-Cell Physiology 2017;313(4):C405-C420. R835737 (2017)
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  • Journal Article Farnoodian M, Halbach C, Slinger C, Pattnaik BR, Sorenson CM, Sheibani N. High glucose promotes the migration of retinal pigment epithelial cells through increased oxidative stress and PEDF expression. American Journal of Physiology-Cell Physiology 2016;311(3):C418-C436. R835737 (2016)
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  • Journal Article Farnoodian M, Wang S, Dietz J, Nickells RW, Sorenson CM, Sheibani N. Negative regulators of angiogenesis: important targets for treatment of exudative AMD. Clinical Science 2017;131(15):1763-1780. R835737 (2017)
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  • Journal Article Farnoodian M, Sorenson CM, Sheibani N. PEDF expression affects the oxidative and inflammatory state of choroidal endothelial cells. American Journal of Physiology-Cell Physiology 2018;314(4):C456-C472. R835737 (2017)
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  • Journal Article Fontana G, Gershlak J, Adamski M, Lee J-S, Matsumoto S, Le HD, Binder B, Wirth J, Gaudette G, Murphy WL. Biofunctionalized plants as diverse biomaterials for human cell culture. Advanced Healthcare Materials 2017;6(8):1601225. R835737 (2016)
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  • Journal Article Garcia K, Chasman D, Roy S, Ane JM. Physiological responses and gene co-expression network of mycorrhizal roots under K+ deprivation. Plant Physiology 2017;173(3):1811-1823. R835737 (2017)
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  • Journal Article Ghanian Z, Staniszewski K, Jamali N, Sepehr R, Wang S, Sorenson CM, Sheibani N, Ranji M. Quantitative assessment of retinopathy using multi-parameter image analysis. Journal of Medical Signals and Sensors 2016;6(2):71-80. R835737 (2016)
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  • Journal Article Gurel Z, Sheibani N. O-Linked β-N-acetylglucosamine (O-GlcNAc) modification: a new pathway to decode pathogenesis of diabetic retinopathy. Clinical Science 2018;132(2):185-198. R835737 (2017)
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  • Journal Article Ibrahim AS, Saleh H, El-Shafey M, Hussein KA, El-Masry K, Baban B, Sheibani N, Wang MH, Tawfik A, Al-Shabrawey M. Targeting of 12/15-lipoxygenase in retinal endothelial cells, but not in monocytes/macrophages, attenuates high glucose-induced retinal leukostasis. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 2017;1862(6):636-645. R835737 (2017)
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  • Journal Article Jamali N, Wang S, Darjatmoko SR, Sorenson CM, Sheibani N. Vitamin D receptor expression is essential during retinal vascular development and attenuation of neovascularization by 1, 25(OH)2D3. PLoS One 2017;12(12):e0190131. R835737 (2017)
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  • Journal Article Jamali N, Sorenson CM, Sheibani N. Vitamin D and regulation of vascular cell function. American Journal of Physiology-Heart and Circulatory Physiology 2017;314(4):H753-H765. R835737 (2017)
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  • Journal Article Khalil AS, Yu X, Xie AW, Fontana G, Umhoefer JM, Johnson HJ, Hookway TA, McDevitt TC, Murphy WL. Functionalization of microparticles with mineral coatings enhances non-viral transfection of primary human cells. Scientific Reports 2017;7(1):14211 (12 pp.). R835737 (2017)
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  • Journal Article Knight GT, Sha J, Ashton RS. Micropatterned, clickable culture substrates enable in situ spatiotemporal control of human PSC-derived neural tissue morphology. Chemical Communications 2015;51(25):5238-5241. R835737 (2015)
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  • Journal Article Knight GT, Lundin BF, Iyer N, Ashton LMT, Sethares WA, Willett RL, Ashton R. Engineering human CNS morphogenesis: controlled induction of singular neural rosette emergence. bioRxiv 229328 [preprint]. R835737 (2017)
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  • Journal Article Lavine JA, Farnoodian M, Wang S, Darjatmoko SR, Wright LS, Gamm DM, Ip MS, Sorenson CM, Sheibani N. β2-adrenergic receptor antagonism attenuates CNV through inhibition of VEGF and IL-6 expression. Investigative Ophthalmology & Visual Science 2017;58(1):299-308. R835737 (2017)
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  • Journal Article Lemke KA, Aghayee A, Ashton RS. Deriving, regenerating, and engineering CNS tissues using human pluripotent stem cells. Current Opinion in Biotechnology 2017;47:36-42. R835737 (2017)
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  • Journal Article Li H, Liu W, Sorenson CM, Sheibani N, Albert DM, Senanayake T, Vinogradov S, Henkin J, Zhang HF. Sustaining intravitreal residence with L-arginine peptide-conjugated nanocarriers. Investigative Ophthalmolology & Visual Science 2017;58(12):5142-5150. R835737 (2017)
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  • Journal Article Lippmann E, Estevez-Silva M, Ashton R. Chemically defined differentiation of human pluripotent stem cells to hindbrain and spinal cord neural stem cells with defined regional identities. Protocol Exchange 2015; 27 pp. R835737 (2015)
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  • Journal Article Marti-Figueroa CR, Ashton RS. The case for applying tissue engineering methodologies to instruct human organoid morphogenesis. Acta Biomaterialia 2017;54:35-44. R835737 (2017)
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  • Journal Article Mofidi Najjar F, Taghavi F, Ghadari R, Sheibani N, Moosavi-Movahedi AA. Destructive effect of non-enzymatic glycation on catalase and remediation via curcumin. Archives of Biochemistry and Biophysics. 2017;630:81-90. R835737 (2017)
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  • Journal Article Morgan MM, Johnson BP, Livingston MK, Schuler LA, Alarid ET, Sung KE, Beebe DJ. Personalized in vitro cancer models to predict therapeutic response: challenges and a framework for improvement. Pharmacology & Therapeutics 2016;165:79-92. R835737 (2016)
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  • Journal Article Morgan MM, Livingston MK, Warrick JW, Stanek EM, Alarid ET, Beebe DJ, Johnson BP. Mammary fibroblasts reduce apoptosis and speed estrogen-induced hyperplasia in an organotypic MCF7-derived duct model. Scientific Reports 2018;8(1):7139 (13 pp.). R835737 (2017)
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  • Journal Article Nguyen EH, Daly WT, Le NN, Farnoodian M, Belair DG, Schwartz MP, Lebakken CS, Ananiev GE, Saghiri MA, Knudsen TB, Sheibani N, Murphy WL. Versatile synthetic alternatives to Matrigel for vascular toxicity screening and stem cell expansion. Nature Biomedical Engineering 2017l;1(7):0096. R835737 (2016)
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  • Journal Article Piscopo NJ, Mueller KP, Das A, Hematti P, Murphy WL, Palecek SP, Capitini CM, Saha K. Bioengineering solutions for manufacturing challenges in CAR T cells. Biotechnology Journal 2018;13(2):1700095 (10 pp.). R835737 (2017)
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  • Journal Article Price TO, Sheibani N, Shah GN. Regulation of high glucose-induced apoptosis of brain pericytes by mitochondrial CA VA: a specific target for prevention of diabetic cerebrovascular pathology. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2017;1863(4):929-935. R835737 (2017)
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  • Journal Article Regier MC, Montanez-Sauri SI, Schwartz MP, Murphy WL, Beebe DJ, Sung KE. The influence of biomaterials on cytokine production in 3D cultures. Biomacromolecules 2017;18(3):709-718. R835737 (2016)
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  • Journal Article Ren J, Liu Z, Wang Q, Giles J, Greenberg J, Sheibani N, Kent KC, Liu B. Andrographolide ameliorates abdominal aortic aneurysm progression by inhibiting inflammatory cell infiltration through downregulation of cytokine and integrin expression. Journal of Pharmacology and Experimental Therapeutics 2016;356(1):137-147. R835737 (2016)
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  • Journal Article Roy S, Sridharan R. Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes. Genome Research 2017;27(7):1250-1262. R835737 (2017)
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  • Journal Article Saghiri MA, Orangi J, Asatourian A, Sorenson CM, Sheibani N. Functional role of inorganic trace elements in angiogenesis part III: (Ti, Li, Ce, As, Hg, Va, Nb and Pb). Critical Reviews in Oncology/Hematology 2016;98:290-301. R835737 (2016)
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  • Journal Article Saghiri MA, Asatourian A, Garcia-Godoy F, Sheibani N. The role of angiogenesis in implant dentistry part I: review of titanium alloys, surface characteristics and treatments. Medicina Oral, Patología Oral y Cirugía Bucal 2016;21(4):e514-e525. R835737 (2016)
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  • Journal Article Saghiri MA, Asatourian A, Garcia-Godoy F, Sheibani N. The role of angiogenesis in implant dentistry part II: the effect of bone-grafting and barrier membrane materials on angiogenesis. Medicina Oral, Patología Oral y Cirugía Bucal 2016;21(4):e526-e537. R835737 (2016)
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  • Journal Article Saghiri MA, Asatourian A, Garcia-Godoy F, Sheibani N. Effect of biomaterials on angiogenesis during vital pulp therapy. Dental Materials Journal 2016;35(5):701-709. R835737 (2016)
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  • Journal Article Saghiri MA, Orangi J, Asatourian A, Gutmann JL, Garcia-Godoy F, Lotfi M, Sheibani N. Calcium silicate-based cements and functional impacts of various constituents. Dental Materials Journal 2017;36(1):8-18. R835737 (2016)
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  • Journal Article Saghiri MA, Asatourian A, Gurel Z, Sorenson CM, Sheibani N. Bcl-2 expression is essential for development and normal physiological properties of tooth hard tissue and saliva production. Experimental Cell Research 2017;358(2):94-100. R835737 (2017)
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  • Journal Article Siahpirani A, Roy S. A prior-based integrative framework for functional transcriptional regulatory network inference. Nucleic Acids Research 2017;45(4):e21 (22 pp.). R835737C005 (2017)
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  • Journal Article Stallcop LE, Alvarez-Garcia YR, Reyes-Ramos AM, Ramos-Cruz KP, Morgan MM, Shi Y, Li L, Beebe DJ, Domenech M, Warrick JW. Razor-printed sticker microdevices for cell-based applications. Lab on a Chip 2018;18(3):451-462. R835737 (2017)
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  • Journal Article Xie AW, Binder BYK, Khalil AS, Schmitt SK, Johnson HJ, Zacharias NA, Murphy WL. Controlled self-assembly of stem cell aggregates instructs pluripotency and lineage bias. Scientific Reports 2017;7(1):14070 (15 pp.). R835737 (2017)
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  • Journal Article Ye G-J, Budzynski E, Sonnentag P, Nork TM, Sheibani N, Gurel Z, Boye SL, Peterson JJ, Boye SE, Hauswirth WW, Chulay JD. Cone-specific promoters for gene therapy of achromatopsia and other retinal diseases. Human Gene Therapy 2016;27(1):72-82. R835737 (2016)
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  • Journal Article Yu X, Biedrzycki AH, Khalil AS, Hess D, Umhoefer JM, Markel MD, Murphy WL. Nanostructured mineral coatings stabilize proteins for therapeutic delivery. Advanced Materials 2017;29(33):1701255. R835737 (2017)
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  • Journal Article Zanotelli MR, Ardalani H, Zhang J, Hou Z, Nguyen EH, Swanson S, Nguyen BK, Bolin J, Elwell A, Bischel LL, Xie AW, Stewart R, Beebe DJ, Thomson JA, Schwartz MP, Murphy WL. Stable engineered vascular networks from human induced pluripotent stem cell-derived endothelial cells cultured in synthetic hydrogels. Acta Biomaterialia 2016;35:32-41. R835737 (2015)
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  • Journal Article Zhang J, Schwartz MP, Hou Z, Bai Y, Ardalani H, Swanson S, Steill J, Ruotti V, Elwell A, Nguyen BK, Bolin J, Stewart R, Thomson JA, Murphy WL. A genome-wide analysis of human pluripotent stem cell-derived endothelial cells in 2D or 3D culture. Stem Cell Reports 2017;8(4):907-918. R835737 (2016)
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  • Journal Article Zhang J, Chu LF, Hou Z, Schwartz MP, Hacker T, Vickerman V, Swanson S, Leng N, Nguyen BK, Elwell A, Bolin J, Brown ME, Stewart R, Burlingham WH, Murphy WL, Thomson JA. Functional characterization of human pluripotent stem cell-derived arterial endothelial cells. Proceedings of the National Academy of Sciences of the United States of America 2017;114(30):E6072-E6078. R835737 (2017)
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  • Journal Article Roy S, Sridharan R. Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes. Genome Research April 19, 2017 [epub ahead of print]. R835737C005 (2016)
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  • Supplemental Keywords:

    Biomaterials; Microfluidics; Self-Assembly; Genomics; High Throughput Screening; High  Content Microscopy; Bioinformatics; Machine Learning

    Progress and Final Reports:

  • 2015 Progress Report
  • 2016 Progress Report
  • 2017 Progress Report
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R835737C001 Liver MAPs
    R835737C002 Brain MAPs
    R835737C003 Cancer MAPs: A 3D Organotypic Microfluidic Culture System to Identify Chemicals that Impact Progression and Development of Breast Cancer
    R835737C004 Vascular MAPs: Vascular and Neurovascular Tissue Models
    R835737C005 Pathway Analysis Core