I. Kinetic Image Cytometry:

  1. Wahlquist, C., Jeong, D., Rojas-Munoz, A., Kho, C., Lee, A., Mitsuyama, S., van Mil, A., Park, W.J., Sluijter, J.P., Doevendans, P.A., Hajjar, R.J. & Mercola, M. Inhibition of miR-25 improves cardiac contractility in the failing heart. Nature 508, 531-535 (2014).
  2. Cerignoli, F., Charlot, D., Whittaker, R., Ingermanson, R., Gehalot, P., Savchenko, A., Gallacher, D.J., Towart, R., Price, J.H., McDonough, P.M. & Mercola, M. High throughput measurement of Ca2+ dynamics for drug risk assessment in human stem cell-derived cardiomyocytes by kinetic image cytometry. J Pharmacol Toxicol Methods 66, 246-256 (2012).
  3. Islas, J.F., Liu, Y., Weng, K.C., Robertson, M.J., Zhang, S., Prejusa, A., Harger, J., Tikhomirova, D., Chopra, M., Iyer, D., Mercola, M., Oshima, R.G., Willerson, J.T., Potaman, V.N. & Schwartz, R.J. Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors. Proceedings of the National Academy of Sciences of the United States of America 109, 13016-13021 (2012).
  4. Charlot, D., Campa, V., Azimi, B., Mercola, M., Ingermanson, R., McDonough, P.M. & Price, J.H. Automated calcium measurements in live cardiomyocytes. in 5th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, Link. 316-319 (2008).

II. IC100 and IC200:

  1. Bharadwaj, U., Eckols, T.K., Kolosov, M., Kasembeli, M.M., Adam, A., Torres, D., Zhang, X., Dobrolecki, L.E., Wei, W., Lewis, M.T., Dave, B., Chang, J.C., Landis, M.D., Creighton, C.J., Mancini, M.A. & Tweardy, D.J. Drug-repositioning screening identified piperlongumine as a direct STAT3 inhibitor with potent activity against breast cancer. Oncogene 0(2014).
  2. Bolt, M.J., Stossi, F., Callison, A.M., Mancini, M.G., Dandekar, R. & Mancini, M.A. Systems level-based RNAi screening by high content analysis identifies UBR5 as a regulator of estrogen receptor-alpha protein levels and activity. Oncogene (2014).
  3. Chung, T.D. Collaborative pre-competitive preclinical drug discovery with academics and pharma/biotech partners at Sanford|Burnham: infrastructure, capabilities & operational models. Combinatorial chemistry & high throughput screening 17, 272-289 (2014).
  4. Stossi, F., Bolt, M.J., Ashcroft, F.J., Lamerdin, J.E., Melnick, J.S., Powell, R.T., Dandekar, R.D., Mancini, M.G., Walker, C.L., Westwick, J.K. & Mancini, M.A. Defining estrogenic mechanisms of bisphenol A analogs through high throughput microscopy-based contextual assays. Chemistry & biology 21, 743-753 (2014).
  5. Large, M.J., Wetendorf, M., Lanz, R.B., Hartig, S.M., Creighton, C.J., Mancini, M.A., Kovanci, E., Lee, K.F., Threadgill, D.W., Lydon, J.P., Jeong, J.W. & DeMayo, F.J. The epidermal growth factor receptor critically regulates endometrial function during early pregnancy. PLoS genetics 10, e1004451 (2014).
  6. Bolt, M.J., Stossi, F., Newberg, J.Y., Orjalo, A., Johansson, H.E. & Mancini, M.A. Coactivators enable glucocorticoid receptor recruitment to fine-tune estrogen receptor transcriptional responses. Nucleic acids research 41, 4036-4048 (2013).
  7. Castro, D.J., Maurer, J., Hebbard, L. & Oshima, R.G. ROCK1 inhibition promotes the self-renewal of a novel mouse mammary cancer stem cell. Stem cells 31, 12-22 (2013).
  8. Kostrominova, T.Y., Reiner, D.S., Haas, R.H., Ingermanson, R. & McDonough, P.M. Automated methods for the analysis of skeletal muscle fiber size and metabolic type. International review of cell and molecular biology 306, 275-332 (2013).
  9. McDonough, P.M., Maciejewski-Lenoir, D., Hartig, S.M., Hanna, R.A., Whittaker, R., Heisel, A., Nicoll, J.B., Buehrer, B.M., Christensen, K., Mancini, M.G., Mancini, M.A., Edwards, D.P. & Price, J.H. Differential phosphorylation of perilipin 1A at the initiation of lipolysis revealed by novel monoclonal antibodies and high content analysis. PloS one 8, e55511 (2013).
  10. Prigozhina, N.L., Heisel, A.J., Seldeen, J.R., Cosford, N.D. & Price, J.H. Amphiphilic suramin dissolves Matrigel, causing an 'inhibition' artefact within in vitro angiogenesis assays. International journal of experimental pathology 94, 412-417 (2013).
  11. Dasgupta, I., Tanifum, E.A., Srivastava, M., Phatak, S.S., Cavasotto, C.N., Analoui, M. & Annapragada, A. Non inflammatory boronate based glucose-responsive insulin delivery systems. PloS one 7, e29585 (2012).
  12. Ding, Z., German, P., Bai, S., Feng, Z., Gao, M., Si, W., Sobieski, M.M., Stephan, C.C., Mills, G.B. & Jonasch, E. Agents that stabilize mutated von Hippel-Lindau (VHL) protein: results of a high-throughput screen to identify compounds that modulate VHL proteostasis. Journal of biomolecular screening 17, 572-580 (2012).
  13. Hartig, S.M., He, B., Newberg, J.Y., Ochsner, S.A., Loose, D.S., Lanz, R.B., McKenna, N.J., Buehrer, B.M., McGuire, S.E., Marcelli, M. & Mancini, M.A. Feed-forward inhibition of androgen receptor activity by glucocorticoid action in human adipocytes. Chemistry & biology 19, 1126-1141 (2012).
  14. Slattery, S.D., Newberg, J.Y., Szafran, A.T., Hall, R.M., Brinkley, B.R. & Mancini, M.A. A framework for image-based classification of mitotic cells in asynchronous populations. Assay and drug development technologies 10, 161-178 (2012).
  15. Uray, I.P., Rodenberg, J.M., Bissonnette, R.P., Brown, P.H. & Mancini, M.A. Cancer-preventive rexinoid modulates neutral lipid contents of mammary epithelial cells through a peroxisome proliferator-activated receptor gamma-dependent mechanism. Molecular pharmacology 81, 228-238 (2012).
  16. Zhang, X., Bolt, M., Guertin, M.J., Chen, W., Zhang, S., Cherrington, B.D., Slade, D.J., Dreyton, C.J., Subramanian, V., Bicker, K.L., Thompson, P.R., Mancini, M.A., Lis, J.T. & Coonrod, S.A. Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor alpha target gene activation. Proceedings of the National Academy of Sciences of the United States of America 109, 13331-13336 (2012).
  17. Ashcroft, F.J., Newberg, J.Y., Jones, E.D., Mikic, I. & Mancini, M. High content imaging-based assay to classify estrogen receptor-alpha ligands based on defined mechanistic outcomes. Gene (2011).
  18. Hartig, S.M., He, B., Long, W., Buehrer, B.M. & Mancini, M.A. Homeostatic levels of SRC-2 and SRC-3 promote early human adipogenesis. J Cell Biol 192, 55-67 (2011).
  19. Prigozhina, N.L., Heisel, A., Wei, K., Noberini, R., Hunter, E.A., Calzolari, D., Seldeen, J.R., Pasquale, E.B., Ruiz-Lozano, P., Mercola, M. & Price, J.H. Characterization of a novel angiogenic model based on stable, fluorescently labelled endothelial cell lines amenable to scale-up for high content screening. Biol Cell 103, 467-481 (2011).
  20. Quintavalle, M., Elia, L., Price, J.H., Heynen-Genel, S. & Courtneidge, S.A. A cell-based high-content screening assay reveals activators and inhibitors of cancer cell invasion. Science signaling 4, ra49 (2011).
  21. Yip, K.W., Cuddy, M., Pinilla, C., Giulanotti, M., Heynen-Genel, S., Matsuzawa, S. & Reed, J.C. A high-content screening (HCS) assay for the identification of chemical inducers of PML oncogenic domains (PODs). Journal of biomolecular screening 16, 251-258 (2011).
  22. Garcia-Becerra, R., Berno, V., Ordaz-Rosado, D., Sharp, Z.D., Cooney, A.J., Mancini, M.A. & Larrea, F. Ligand-induced large-scale chromatin dynamics as a biosensor for the detection of estrogen receptor subtype selective ligands. Gene 458, 37-44 (2010).
  23. Kiselyuk, A., Farber-Katz, S., Cohen, T., Lee, S.H., Geron, I., Azimi, B., Heynen-Genel, S., Singer, O., Price, J., Mercola, M., Itkin-Ansari, P. & Levine, F. Phenothiazine neuroleptics signal to the human insulin promoter as revealed by a novel high-throughput screen. Journal of biomolecular screening 15, 663-670 (2010).
  24. McDonough, P.M., Ingermanson, R.S., Loy, P.A., Koon, E.D., Whittaker, R., Laris, C.A., Hilton, J.M., Nicoll, J.B., Buehrer, B.M. & Price, J.H. Quantification of Hormone Sensitive Lipase Phosphorylation and Colocalization with Lipid Droplets in Murine 3T3L1 and Human Subcutaneous Adipocytes via Automated Digital Microscopy and High-Content Analysis. Assay and drug development technologies (2010).
  25. Narayanan, R., Yepuru, M., Szafran, A.T., Szwarc, M., Bohl, C.E., Young, N.L., Miller, D.D., Mancini, M.A. & Dalton, J.T. Discovery and mechanistic characterization of a novel selective nuclear androgen receptor exporter for the treatment of prostate cancer. Cancer Res 70, 842-851 (2010).
  26. Whittaker, R., Loy, P.A., Sisman, E., Suyama, E., Aza-Blanc, P., Ingermanson, R.S., Price, J.H. & McDonough, P.M. Identification of MicroRNAs that control lipid droplet formation and growth in hepatocytes via high-content screening. Journal of biomolecular screening 15, 798-805 (2010).
  27. Zou, J., Ganji, S., Pass, I., Ardecky, R., Peddibhotla, M., Loribelle, M., Heynen-Genel, S., Sauer, M., Pass, I., Vasile, S., Suyama, E., Malany, S., Mangravita-Novo, A., Vicchiarelli, M., McAnally, D., Cheltsov, A., Derek, S., Shi, S., Su, Y., Zeng, F.Y., Pinkerton, A.B., Smith, L.H., Kim, S., Ngyuen, H., Zeng, F.Y., Diwan, J., Heisel, A.J., Coleman, R., McDonough, P.M. & Chung, T.D.Y. Potent inhibitors of lipid droplet formation. in Probe Reports from the NIH Molecular Libraries Program (Bethesda (MD), 2010).
  28. Buck, T.E., Rao, A., Coelho, L.P., Fuhrman, M.H., Jarvik, J.W., Berget, P.B. & Murphy, R.F. Cell cycle dependence of protein subcellular location inferred from static, asynchronous images. Conf Proc IEEE Eng Med Biol Soc 2009, 1016-1019 (2009).
  29. Coelho, L.P., Shariff, A. & Murphy, R.F. Nuclear Segmentation in Microscope Cell Images: A Hand-Segmented Dataset and Comparison of Algorithms. Proc IEEE Int Symp Biomed Imaging 5193098, 518-521 (2009).
  30. Giordano, C., Cui, Y., Barone, I., Ando, S., Mancini, M.A., Berno, V. & Fuqua, S.A. Growth factor-induced resistance to tamoxifen is associated with a mutation of estrogen receptor alpha and its phosphorylation at serine 305. Breast Cancer Res Treat 119, 71-85 (2009).
  31. Heynen-Genel, S. & Price, J. Cytometric Features of Fluorescently Labeled Nuclei for Cell Classification. in Handbook of Medical Image Processing and Analysis, Vol. 1 (ed. Bankman, I.) 453-463 (Academic Press, 2009).
  32. McDonough, P.M., Agustin, R.M., Ingermanson, R.S., Loy, P.A., Buehrer, B.M., Nicoll, J.B., Prigozhina, N.L., Mikic, I. & Price, J.H. Quantification of Lipid Droplets and Associated Proteins in Cellular Models of Obesity via High-Content/High-Throughput Microscopy and Automated Image Analysis. Assay and drug development technologies (2009).
  33. Slattery, S.D., Mancini, M.A., Brinkley, B.R. & Hall, R.M. Aurora-C kinase supports mitotic progression in the absence of Aurora-B. Cell Cycle 8, 2984-2994 (2009).
  34. Szafran, A.T., Hartig, S., Sun, H., Uray, I.P., Szwarc, M., Shen, Y., Mediwala, S.N., Bell, J., McPhaul, M.J., Mancini, M.A. & Marcelli, M. Androgen receptor mutations associated with androgen insensitivity syndrome: a high content analysis approach leading to personalized medicine. PloS one 4, e8179 (2009).
  35. Willems, E., Bushway, P.J. & Mercola, M. Natural and synthetic regulators of embryonic stem cell cardiogenesis. Pediatr Cardiol 30, 635-642 (2009).
  36. Berno, V., Amazit, L., Hinojos, C., Zhong, J., Mancini, M. G., Sharp, Z. D., Mancini, M. A. Activation of estrogen receptor-alpha by E2 or EGF induces temporally distinct patterns of large-scale chromatin modification and mRNA transcription. PloS one 3, e2286 (2008).
  37. Bushway, P.J., Mercola, M. & Price, J.H. A comparative analysis of standard microtiter plate reading versus imaging in cellular assays. Assay and drug development technologies 6, 557-567 (2008).
  38. Szafran, A.T., Szwarc, M., Marcelli, M. & Mancini, M.A. Androgen receptor functional analyses by high throughput imaging: determination of ligand, cell cycle, and mutation-specific effects. PloS one 3, e3605 (2008).
  39. Amazit, L., Pasini, L., Szafran, A.T., Berno, V., Wu, R.C., Mielke, M., Jones, E.D., Mancini, M.G., Hinojos, C.A., O'Malley, B.W. & Mancini, M.A. Regulation of SRC-3 intercompartmental dynamics by estrogen receptor and phosphorylation. Molecular and cellular biology 27, 6913-6932 (2007).
  40. Garcia Osuna, E., Hua, J., Bateman, N.W., Zhao, T., Berget, P.B. & Murphy, R.F. Large-scale automated analysis of location patterns in randomly tagged 3T3 cells. Ann Biomed Eng 35, 1081-1087 (2007).
  41. Huang, Y., Qiu, J., Dong, S., Redell, M.S., Poli, V., Mancini, M.A. & Tweardy, D.J. Stat3 isoforms, alpha and beta, demonstrate distinct intracellular dynamics with prolonged nuclear retention of Stat3beta mapping to its unique C-terminal end. The Journal of biological chemistry 282, 34958-34967 (2007).
  42. Prigozhina, N.L., Zhong, L., Hunter, E.A., Mikic, I., Callaway, S., Roop, D.R., Mancini, M.A., Zacharias, D.A., Price, J.H. & McDonough, P.M. Plasma membrane assays and three-compartment image cytometry for high content screening. Assay and drug development technologies 5, 29-48 (2007).
  43. Berno, V., Hinojos, C.A., Amazit, L., Szafran, A.T. & Mancini, M.A. High-resolution, high-throughput microscopy analyses of nuclear receptor and coregulator function. Methods Enzymol 414, 188-210 (2006).
  44. Cho, C.Y., Koo, S.H., Wang, Y., Callaway, S., Hedrick, S., Mak, P.A., Orth, A.P., Peters, E.C., Saez, E., Montminy, M., Schultz, P.G. & Chanda, S.K. Identification of the tyrosine phosphatase PTP-MEG2 as an antagonist of hepatic insulin signaling. Cell Metab 3, 367-378 (2006).
  45. Marcelli, M., Stenoien, D.L., Szafran, A.T., Simeoni, S., Agoulnik, I.U., Weigel, N.L., Moran, T., Mikic, I., Price, J.H. & Mancini, M.A. Quantifying effects of ligands on androgen receptor nuclear translocation, intranuclear dynamics, and solubility. J Cell Biochem 98, 770-788 (2006).
  46. Mikic, I., Planey, S., Zhang, J., Ceballos, C., Seron, T., von Massenbach, B., Watson, R., Callaway, S., McDonough, P.M., Price, J.H., Hunter, E. & Zacharias, D. A live cell, image-based approach to understanding the enzymology and pharmacology of 2-bromopalmitate and palmitoylation. Methods Enzymol 414, 150-187 (2006).
  47. Mukherji, M., Bell, R., Supekova, L., Wang, Y., Orth, A.P., Batalov, S., Miraglia, L., Huesken, D., Lange, J., Martin, C., Sahasrabudhe, S., Reinhardt, M., Natt, F., Hall, J., Mickanin, C., Labow, M., Chanda, S.K., Cho, C.Y. & Schultz, P.G. Genome-wide functional analysis of human cell-cycle regulators. Proceedings of the National Academy of Sciences of the United States of America 103, 14819-14824 (2006).
  48. Prigozhina, N.L. & Waterman-Storer, C.M. Decreased polarity and increased random motility in PtK1 epithelial cells correlate with inhibition of endosomal recycling. J Cell Sci 119, 3571-3582 (2006).
  49. Sharp, Z.D., Mancini, M.G., Hinojos, C.A., Dai, F., Berno, V., Szafran, A.T., Smith, K.P., Lele, T.P., Ingber, D.E. & Mancini, M.A. Estrogen-receptor-alpha exchange and chromatin dynamics are ligand- and domain-dependent. J Cell Sci 119, 4101-4116 (2006).
  50. Shen, F., Hodgson, L., Rabinovich, A., Pertz, O., Hahn, K. & Price, J.H. Functional proteometrics for cell migration. Cytometry. Part A : the journal of the International Society for Analytical Cytology 69, 563-572 (2006).
  51. Shen, F. & Price, J.H. Toward complete laser ablation of melanoma contaminant cells in a co-culture outgrowth model via image cytometry. Cytometry. Part A : the journal of the International Society for Analytical Cytology 69, 573-581 (2006).
  52. Wilson, C.J., Si, Y., Thompsons, C.M., Smellie, A., Ashwell, M.A., Liu, J.F., Ye, P., Yohannes, D. & Ng, S.C. Identification of a small molecule that induces mitotic arrest using a simplified high-content screening assay and data analysis method. Journal of biomolecular screening 11, 21-28 (2006).
  53. Harada, J.N., Bower, K.E., Orth, A.P., Callaway, S., Nelson, C.G., Laris, C., Hogenesch, J.B., Vogt, P.K. & Chanda, S.K. Identification of novel mammalian growth regulatory factors by genome-scale quantitative image analysis. Genome Res 15, 1136-1144 (2005).
  54. Morelock, M.M., Hunter, E.A., Moran, T.J., Heynen, S., Laris, C., Thieleking, M., Akong, M., Mikic, I., Callaway, S., DeLeon, R.P., Goodacre, A., Zacharias, D. & Price, J.H. Statistics of assay validation in high throughput cell imaging of nuclear factor kappaB nuclear translocation. Assay and drug development technologies 3, 483-499 (2005).
  55. Price, J.H., Goodacre, A., Hahn, K., Hodgson, L., Hunter, E.A., Krajewski, S., Murphy, R.F., Rabinovich, A., Reed, J.C. & Heynen, S. Advances in molecular labeling, high throughput imaging and machine intelligence portend powerful functional cellular biochemistry tools. J Cell Biochem Suppl 39, 194-210 (2002).
  56. Bajaj, S., Welsh, J.B., Leif, R.C. & Price, J.H. Ultra-rare-event detection performance of a custom scanning cytometer on a model preparation of fetal nRBCs. Cytometry 39, 285-294 (2000).

III. CyteSeer Software Platform

  1. Chung, C.H., Miller, A., Panopoulos, A., Hao, E., Margolis, R., Terskikh, A. & Levine, F. Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not beta-cell, regeneration. Physiological reports 2(2014).
  2. Bhavane, R., Badea, C., Ghaghada, K.B., Clark, D., Vela, D., Moturu, A., Annapragada, A., Johnson, G.A., Willerson, J.T. & Annapragada, A. Dual-energy computed tomography imaging of atherosclerotic plaques in a mouse model using a liposomal-iodine nanoparticle contrast agent. Circulation. Cardiovascular imaging 6, 285-294 (2013).
  3. Mediwala, S.N., Sun, H., Szafran, A.T., Hartig, S.M., Sonpavde, G., Hayes, T.G., Thiagarajan, P., Mancini, M.A. & Marcelli, M. The activity of the androgen receptor variant AR-V7 is regulated by FOXO1 in a PTEN-PI3K-AKT-dependent way. The Prostate 73, 267-277 (2013).
  4. Zhang, Y., Davis, C., Sakellariou, G.K., Shi, Y., Kayani, A.C., Pulliam, D., Bhattacharya, A., Richardson, A., Jackson, M.J., McArdle, A., Brooks, S.V. & Van Remmen, H. CuZnSOD gene deletion targeted to skeletal muscle leads to loss of contractile force but does not cause muscle atrophy in adult mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27, 3536-3548 (2013).
  5. Colas, A.R., McKeithan, W.L., Cunningham, T.J., Bushway, P.J., Garmire, L.X., Duester, G., Subramaniam, S. & Mercola, M. Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ layer formation during early embryogenesis. Genes & development 26, 2567-2579 (2012).
  6. Tanifum, E.A., Dasgupta, I., Srivastava, M., Bhavane, R.C., Sun, L., Berridge, J., Pourgarzham, H., Kamath, R., Espinosa, G., Cook, S.C., Eriksen, J.L. & Annapragada, A. Intravenous delivery of targeted liposomes to amyloid-beta pathology in APP/PSEN1 transgenic mice. PloS one 7, e48515 (2012).
  7. Willems, E., Cabral-Teixeira, J., Schade, D., Cai, W., Reeves, P., Bushway, P.J., Lanier, M., Walsh, C., Kirchhausen, T., Izpisua Belmonte, J.C., Cashman, J. & Mercola, M. Small molecule-mediated TGF-beta type II receptor degradation promotes cardiomyogenesis in embryonic stem cells. Cell stem cell 11, 242-252 (2012).
  8. Larkin, L.M., Davis, C.S., Sims-Robinson, C., Kostrominova, T.Y., Van Remmen, H., Richardson, A., Feldman, E.L. & Brooks, S.V. Skeletal muscle weakness due to deficiency of CuZn-superoxide dismutase is associated with loss of functional innervation. American journal of physiology. Regulatory, integrative and comparative physiology 301, R1400-1407 (2011).
  9. Willems, E., Spiering, S., Davidovics, H., Lanier, M., Xia, Z., Dawson, M., Cashman, J. & Mercola, M. Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm. Circulation research 109, 360-364 (2011).
  10. Sun, S., Sprenger, C.C., Vessella, R.L., Haugk, K., Soriano, K., Mostaghel, E.A., Page, S.T., Coleman, I.M., Nguyen, H.M., Sun, H., Nelson, P.S. & Plymate, S.R. Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. The Journal of clinical investigation 120, 2715-2730 (2010).
  11. McKeithan, W.L., Colas, A.R., Bushway, P.J., Ray, S. & Mercola, M. Serum-Free Generation of Multipotent Mesoderm (Kdr+) Progenitor Cells in Mouse Embryonic Stem Cells for Functional Genomics Screening. in Current Protocols in Stem Cell Biology (John Wiley & Sons, Inc., 2007).