Grantee Research Project Results
2015 Progress Report: Human Models for Analysis of Pathways (H MAPs) Center
EPA Grant Number: R835737Center: 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 , Thomson, James , Sheibani, Nader , Roy, Sushmita
Current Investigators: Murphy, William L , Thomson, James , McIntosh, Brian , Vickerman-Kelley, Vernella , Roy, Sushmita , Beebe, David , Sheibani, Nader , Ashton, Randolph S
Institution: University of Wisconsin - Madison
EPA Project Officer: Callan, Richard
Project Period: December 1, 2014 through November 30, 2018 (Extended to November 30, 2019)
Project Period Covered by this Report: December 1, 2014 through November 30,2015
Project Amount: $5,999,600
RFA: Organotypic Culture Models for Predictive Toxicology Center (2013) RFA Text | Recipients Lists
Research Category: Chemical Safety for Sustainability
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. The H-MAPs Center will be committed to transforming chemical toxicity testing by taking advantage of advances in biology, biotechnology, and computer modeling. The overall objective of this program is to create transformative organotypic human models in formats that offer unique practical capabilities for toxin screening and pathway analysis. 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 brings 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.
Project 1: Liver MAPs
Objective 1: Identify regulator networks that control liver maturation.
Objective 2: Screen for factors that promote human ES/iPSC cell-derived hepatocyte maturation.
Objective 3: Optimize 3D organotypic cultures of human ES cell-derived hepatocytes with mature metabolic function.
Project 2: Brain MAPs
Objective 1: Generate region-specific, hCNS tissues with organotypic phenotype diversity
Objective 2: Use a microfluidic culture platform to create 3D organotypic hCNS tissues
Objective 3: Establish a pipeline for phenotype-specific, quantitative high-throughput neurotoxicity studies
Project 3: Cancer MAPs
Objective 1: Optimize and automate a synchronous microfluidic 3D in vitro cancer model to be used for chemical library screening
Objective 2: Develop the AOP based model (ER-mediated IDC) by utilizing quantitative physiological and molecular endpoints to identify key steps between the molecular initiating even (Estrogen Receptor ligand binding) to the adverse outcome (IDC) in the 3D
microfluidic platform
Objective 3: Conduct screens using chemicals from the ToxCast library in the staged organotypic system to identify chemicals that promote key events in the ER-mediated IDC AOP
Project 4: Vascular MAPs
Objective 1: Develop organotypic human vascular and neurovascular models
Objective 2: Identify adverse outcome pathways associated with environmental toxins in the developed models
Objective 3: Determine the critical elements of the organotypic response, critical cell types, and tissue architecture
Project 5: Pathway Analysis Core
The overarching goal of our Pathway Analysis Core is to provide an integrated understanding of cellular response to environmental perturbations by developing novel network biology tools that are applicable to variety of cell types and tissue models. Our specific aims are to develop methods that (1) integrate temporal dynamics in regulatory network model reconstruction and (2) identify subnetworks that are perturbed under exposure to changing environmental stimuli. We will apply these methods to dissect regulatory networks of tissue and cell-type specific responses to small molecules and toxins from the central nervous system and liver hepatocyte development. Specifically, the core is developing methods to analyze data measured by the Brain MAPS and Liver MAPS projects.
Progress Summary:
Significant progress has been made pursuant to research milestones laid down in the original grant proposal. The Center's efforts during its first year have produced a total of 22 original research manuscripts published, submitted, or in preparation for near-term submission. Significant strides have been made towards the completion of project milestones, which are reflected in the individual project summaries.
Future Activities:
Planned activities include all activities proposed in the initial Center proposal. In addition, Center activities have led to initiation of a series of new collaborative projects, including:
- Collaborations with EPA staff (Knudsen et al.) related to vascular tissue models and endothelial to mesenchymal transition.
- Collaborations with the EPA STAR Center based at Vanderbilt University on novel neurovascular unit devices/biomaterials (Wikswo et al.).
- New collaborations related to the Human MAPs approach, including Eye MAPs, EMT MAPs, Prostate Cancer MAPs, and Muscle MAPs.
Journal Articles: 81 Displayed | Download in RIS Format
Other center views: | All 215 publications | 82 publications in selected types | All 81 journal articles |
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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. |
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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. |
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Aisenbrey E, Murphy W. Synthetic alternatives to Matrigel. Nature Reviews Materials 2020 |
R835737 (Final) |
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Bakooshli M, Lippmann E, Mulcahy B, Iyer N, Nguyen C, Tung K, Stewart B, van den Dorpel H, Fuehrmann T, Gilbert P, Shoichet M, Bigot A, Pegoraro E, Ahn H, Ginsberg H, Zhen M, Ashton R, Gilbert P. A 3D culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction. DEVELOPMENTAL BIOLOGHY, STEM CELLS AND REGENERATIVE MEDICINE 2019;8(e44530) |
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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. |
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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. |
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Belair DG, Miller MJ, Wang S, Darjatmoko SR, Binder BYK, Sheibani N, Murphy WL. Differential regulation of angiogenesis using degradable VEGF-binding microspheres. Biomaterials 2016;93:27-37. |
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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) R835737 (2016) R835737 (2017) R835737C004 (2015) |
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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 Biology2016;12(7):e1005013. |
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Chasman D, Fotuhi Siahpirani A, Roy S. Network-based approaches for analysis of complex biological systems. Current Opinion in Biotechnology 2016;39:157-166. |
R835737 (2015) R835737 (2016) R835737 (2017) R835737C005 (2015) |
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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) R835737C004 (2017) R835737C005 (2016) R835737C005 (2017) |
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Clements AE, Groves ER, Chamberlain CS, Vanderby R, Murphy WL. Microparticles locally deliver active interleukin-1 receptor antagonist in vivo. Advanced Healthcare Materials 2018;7(16):1800263. |
R835737 (Final) |
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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) R835737 (2017) R835737C004 (2016) |
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Estevez-Silva M, Sreeram A, Cuskey S, Fedorchak N, Layer N, Ashton R. Single-injection ex ovo transplantation method for broad spinal cord engraftment of human pluripotent stem cell-derived motor neurons. JOURNAL OF NEUROSCIENCE METHODS 2018;298:16-23 |
R835737 (Final) |
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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. |
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Falero-Perez J, Sorenson C, Sheibani N. Cyp1b1-deficient retinal astrocytes are more proliferative and migratory and are protected from oxidative stress and inflammation. AMERICAN JOURNAL OF PHYSIOLOGY 2019;306(6):C767-C781 |
R835737 (Final) |
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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. |
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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. |
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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. |
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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. |
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Garcia K, Chasman D, Roy S, Ane J-M. Physiological responses and gene co-expression network of mycorrhizal roots under K+ deprivation. Plant Physiology 2017;173(3):1811-1823. |
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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. |
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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. |
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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. |
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Iyer N, Shin J, Cuskey S, Tian Y, Nicol N, Doersch T, Seipel F, McCalla S, Roy S, Ashton R. Modular derivation of diverse, regionally discrete human posterior CNS neurons enables discovery of transcriptomic patterns. SCIENCE ADVANCES 2022;8(39):eabn7430 |
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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)2 D3 . PLoS One 2017;12(12):e0190131. |
R835737 (2017) |
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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. |
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Johnson B, VItek R, Morgan M, Fink D, Beames T, Geiger P, Beebe D, Lipinski R. A Microphysiological Approach to Evaluate Effectors of Intercellular Hedgehog Signaling in Development. Frontiers in Cell and Developmental Biology 2021;9:71. |
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Kauschik G, Gupta K, Harms V, Torr E, Evans J, Johnson H, Soref C, Acevedo-Acevedo S, Antosiewicz-Bourget J, Mamott D. Engineered Perineural Vascular Plexus for Modeling Developmental Toxicity. Advanced Healcare Materials 2020;(2000825). |
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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. |
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Khalil A, Yu X, Umhoefer J, Chamberlain C, COnnie S, Wildenauer L, Diarra G, Hacker T, Murphy W. Single-dose mRNA therapy via biomaterial-mediated sequestration of overexpressed proteins. Science Advances 2020;6(27):eaba2422. |
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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. |
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Knight GT, Lundin BF, Iyer N, Ashton LMT, Sethares WA, Willett RM, Ashton RS. Engineering induction of singular neural rosette emergence within jPSC-derived tissues. eLIFE 2018;7:e37549 (23 pp.). |
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Krutty JD, Schmitt SK, Gopalan P, Murphy WL. Surface functionalization and dynamics of polymeric cell culture substrates. Current Opinion in Biotechnology 2016;40:164-169. |
R835737 (2017) |
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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. |
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Lei J, Murphy W, Temenoff J. Combination of Heparin Binding Peptide and Heparin Cell Surface Coatings for Mesenchymal Stem Cell Spheroid Assembly. BIOCONJUGATE CHEMISTRY 2018;29(4):878-884 |
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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. |
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Lewis S, Takimoto T, Mehrvar S, Higuchi H, Doebley A, Stokes G, Sheibani N, Ideda S, Ranji M, Ikeda A. The effect of Tmem135 overexpression on the mouse heart. PLOS ONE 2018;13(8):e0201986 |
R835737 (Final) |
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Li C, Hurley A, Hu W, Warrick J, Lozano G, Ayuso J, Pan W, Handlesman J, Beebe D. Social motility of biofilm-like microcolonies in a gliding bacterium. Nature Communications 2021;12(1). |
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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. |
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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. |
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LIvingston M, Morgan M, Daly W, Murphy W, Johnson B, Virumbrales-Munoz M. Evaluation of PEG-Based Hydrogel Influence on Estrogen-Receptor-Driven Responses in MCF7 Breast Cancer Cells. ACS Publications 2019;5(11):6089-6098. |
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Mahony C, Ashton R, Birk B, Boobis A, Cull T, Datson G, Ewart L, Knudsen T, Manou I, Maurer-Stroh S. New ideas for non-animal approaches to predict repeated-dose systemic toxicity:Report from an EPAA Blue Sky Workshop. Regulatory Toxicology and Pharmacology 2020;114(UNSP 104668). |
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Majumder J, Torr E, Aisenbrey E, Lebakken C, Favreau P, Richards W, Yin Y, Chang Q, Murphy W. Human induced pluripotent stem cell-derived planar neural organoids assembled on synthetic hydrogels. JOURNAL OF TISSUE ENGINEERING 2024;15(20417314241230633) |
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Marti-Figueroa CR, Ashton RS. The case for applying tissue engineering methodologies to instruct human organoid morphogenesis. Acta Biomaterialia 2017;54:35-44. |
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Mezu-Ndubuisi O, Wang Y, Schoephoerster J, Falero_Perez J, Zaitoun I, Sheibani, Gong S. Intravitreal Delivery of VEGF-A(165)-loaded PLGA Microparticles Reduces Retinal Vaso-Obliteration in an In Vivo Mouse Model of Retinopathy of Prematurity. CURRENT EYE RESEARCH 2018;44(Full Text HTML):275-286 |
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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. |
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Molugy K, Harkness T, Carlson-Tevermer J, Prestil R, Piscopo N, Seymour S, Knight G, Ashton R, Saha K. Tracking and Predicting Human Somatic Cell Reprogramming Using Nuclear Characteristics. BIOPHYSICAL JOURNAL 2020;118(9):2086-2102. |
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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. |
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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. |
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Morgan M, Arendt L, Alarid E, Beebe D, Johnson B. Mammary adipose stromal cells derived from obese women reduce sensitivity to the aromatase inhibitor anastrazole in an organotypic breast model. FASEB Journal 2019;33(7):8623-8633. |
R835737 (2018) R835737C003 (Final) |
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Morgan M, Schuler L, Ciciliano J, Johnson B, Alarid E, Beebe D. Modeling chemical effects on breast cancer: the importance of the microenvironment in vitro. Integrative Biology 2020;12(2):21-33 |
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Nguyen EH, Daly WT, Le NNT, 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 2017;1(7):0096. |
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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. |
R835737 (2017) |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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Seirup M, Chu L, Sengupta S, Leng N, Browder H, Kapadia K, Shafer C, Duffin B, Elwell A, Bolin J. Reproducibility across single-cell RNA-seq protocols for spatial ordering analysis. PLOS One 2020;15(9). |
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Seirup M, Sengupta S, Swanson S, McIntosh B, Collins M, Cu L, Cheng Z, Gorkin D, Duffin B, Bolin J, Argus C, Stewart R, Thompson J. Rapid changes in chromatin structure during dedifferentiation of primary hepatocytes in vitro. GENOMICS 2022;114(3):110330. |
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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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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. |
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Virumbrales-Munoz M, Ayuso J, Lacueva A, Randelovic T, Livingston M, Beebe D, Olivan S, Pereboom D, Doblare M, Fernandez L. Enabling cell recovery from 3D cell culture microfluidic devices for tumour microenvironment biomarker profiling. Scientific Reports 2020;10(1):757. |
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Wheeler HE, Ploch SA, Barberia AN, Bonazzola R, Andaleon A, Fotuhi S, Saha A, Battle A, Roy S, Im HK. Imputed gene associations identify replicable trans-acting genes enriched in transcription pathways and complex traits. Genetic Epidemiology 2019. |
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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. |
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Xie A, Zacharias N, Binder B, Murphy W. Controlled aggregation enhances immunomodulatory potential of mesenchymal stromal cell aggregates. Stem Cells Translational Medicine 2021;1(18). |
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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. |
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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. |
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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) R835737 (2016) R835737 (2017) R835737C001 (2017) R835737C004 (2015) |
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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) R835737 (2017) R835737C001 (2017) |
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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 WJ, 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) R835737C001 (2017) |
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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) R835737C005 (2016) |
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Clements AE, Leiferman EM, Chamberlain CS, Vanderby R, Murphy WL. Addition of mineral coated microparticles to soluble interleukin-1 receptor antagonist injected subcutaneously improves and extends systemic interleukin-1 inhibition. Advanced Therapeutics 2018;1(7):1800048. |
R835737 (Final) |
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Ayuso JM, Gillette A, Lugo-Cintrón K, Acevedo-Acevedo S, Gomez I, Morgan M, Heaster T, Wisinski KB, Palecek SP, Skala MC, Beebe DJ. Organotypic microfluidic breast cancer model reveals starvation-induced spatial-temporal metabolic adaptations. EBioMedicine 2018;37:144-157. |
R835737C003 (Final) |
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Khalil AS, Xie AW, Johnson HJ, Murphy WL. Sustained release and protein stabilization reduce the growth factor dosage required for human pluripotent stem cell expansion. Biomaterials 2020:120007. |
R835737 (Final) |
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Supplemental Keywords:
Ductal carcinoma in situ (DCIS), estrogen disrupting chemicals (EDC), mammary duct, microenvironment, microfluidics, stroma, regulatory networks, transcriptional modules, chromatin state, dynamic networks, temporal networks;Progress and Final Reports:
Original Abstract 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
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.