Bio

Professional Education


  • Bachelor of Science, University of California Riverside (1997)
  • Master of Science, University of California Riverside (1998)
  • Master of Science, University of California Riverside, Biochemistry (1998)
  • Bachelor of Science, University of California Riverside, Biochemistry (1997)
  • Doctor of Philosophy, Stanford University, CSB-PHD (2012)

Publications

Journal Articles


  • The Imidazopyridine Derivative JK184 Reveals Dual Roles for Microtubules in Hedgehog Signaling ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Cupido, T., Rack, P. G., Firestone, A. J., Hyman, J. M., Han, K., Sinha, S., Ocasio, C. A., Chen, J. K. 2009; 48 (13): 2321-2324

    Abstract

    Eradicating hedgehogs: The title molecule has been previously identified as a potent inhibitor of the Hedgehog signaling pathway, which gives embryonic cells information needed to develop properly. This molecule is shown to modulate Hedgehog target gene expression by depolymerizing microtubules, thus revealing dual roles of the cytoskeleton in pathway regulation (see figure).

    View details for DOI 10.1002/anie.200805666

    View details for Web of Science ID 000264784400011

    View details for PubMedID 19222062

  • Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Hyman, J. M., Firestone, A. J., Heine, V. M., Zhao, Y., Ocasio, C. A., Han, K., Sun, M., Rack, P. G., Sinha, S., Wu, J. J., Solow-Cordero, D. E., Jiang, J., Rowitch, D. H., Chen, J. K. 2009; 106 (33): 14132-14137

    Abstract

    Inappropriate activation of the Hedgehog (Hh) signaling pathway has been implicated in a diverse spectrum of cancers, and its pharmacological blockade has emerged as an anti-tumor strategy. While nearly all known Hh pathway antagonists target the transmembrane protein Smoothened (Smo), small molecules that suppress downstream effectors could more comprehensively remediate Hh pathway-dependent tumors. We report here four Hh pathway antagonists that are epistatic to the nucleocytoplasmic regulator Suppressor of Fused [Su(fu)], including two that can inhibit Hh target gene expression induced by overexpression of the Gli transcription factors. Each inhibitor has a unique mechanism of action, and their phenotypes reveal that Gli processing, Gli activation, and primary cilia formation are pharmacologically targetable. We further establish the ability of certain compounds to block the proliferation of cerebellar granule neuron precursors expressing an oncogenic form of Smo, and we demonstrate that Hh pathway inhibitors can have tissue-specific activities. These antagonists therefore constitute a valuable set of chemical tools for interrogating downstream Hh signaling mechanisms and for developing chemotherapies against Hh pathway-related cancers.

    View details for DOI 10.1073/pnas.0907134106

    View details for Web of Science ID 000269078700091

    View details for PubMedID 19666565

  • Channel properties of NMDA receptors on magnocellular neuroendocrine cells cultured from the rat supraoptic nucleus BRAIN RESEARCH Curras, M. C., Rack, P. G., Meeker, R. B. 1998; 789 (2): 181-193

    Abstract

    Application of N-methyl-D-aspartate (NMDA) to the supraoptic nucleus of the hypothalamus (SON) generates clustered firing that may be important in hormone release. However, synaptically evoked EPSPs recorded from SON neurons exhibit varying contributions from NMDA receptors. We used the high resolution of single-channel recording to examine the receptor and ion channel properties of NMDA receptors expressed by SON neurons in 'punch' culture. Biocytin introduced into individual neurons during patch clamp recording revealed large (32.1+/-3.3 micron), oblong somas and bipolar extensions typical of magnocellular neuroendocrine cells (MNCs). Rapid application of NMDA (100-300 microM) in the presence of 10 microM glycine to outside-out macropatches resulted in openings with an average conductance of 46. 9 pS and reversal potential of +3.9 mV. Increasing glycine from 0.03 to 30 microM increased the apparent frequency, duration and occurrence of overlapping NMDA-elicited openings. NMDA responses were inhibited by Mg2+ in a voltage-dependent manner and by the NMDA-site antagonist, D-(-)-2-amino-5-phosphonovaleric acid (D-APV). Application of saturating NMDA or glycine alone with the glycine-site antagonist, 5,7-dichlorokynurenate (DCK) or with D-APV, respectively, did not result in agonist-induced openings. NR1 immunoreactivity was observed in large neurons (>25 micron) with MNC-like morphology. These single-channel and immunocytochemical data confirm the presence of functional NR1-containing NMDA receptors in MNCs.

    View details for Web of Science ID 000073565600001

    View details for PubMedID 9573359

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