Bio

Professional Education


  • Doctor of Philosophy, Colorado State University (2014)
  • Bachelor of Science, University of California Santa Cruz (2004)
  • Associate of Arts, De Anza College (2002)

Stanford Advisors


Publications

All Publications


  • CC-401 Promotes ?-Cell Replication via Pleiotropic Consequences of DYRK1A/B Inhibition. Endocrinology Abdolazimi, Y., Lee, S., Xu, H., Allegretti, P., Horton, T. M., Yeh, B., Moeller, H. P., Nichols, R. J., McCutcheon, D., Shalizi, A., Smith, M., Armstrong, N. A., Annes, J. P. 2018

    Abstract

    Pharmacologic expansion of endogenous ?-cells is a promising therapeutic strategy for diabetes. To elucidate the molecular pathways that control ?-cell growth we screened ?2,400 bioactive compounds for rat ?-cell replication-modulating activity. Numerous hit compounds impaired or promoted rat ?-cell replication, including CC-401, an advanced clinical candidate previously characterized as a c-Jun N-terminal kinase (JNK) inhibitor. Surprisingly, CC-401 induced rodent (in vitro and in vivo) and human (in vitro) ?-cell replication via dual specificity tyrosine-phosphorylation-regulated kinases (DYRK1A/B) inhibition. In contrast to rat ?-cells, which were broadly growth responsive to compound treatment, human ?-cell replication was only consistently induced by DYRK1A/B inhibitors. This effect was enhanced by simultaneous glycogen synthase kinase-3? (GSK-3?) or transforming growth factor-? (ALK5/TGF-?) inhibition. Prior work emphasized DYRK1A/B inhibition-dependent activation of nuclear factor of activated T-cells (NFAT) as the primary mechanism of human ?-cell replication induction. However, inhibition of NFAT activity had limited impact on CC-401-induced ?-cell replication. Consequently, we investigated additional effects of CC-401-dependent DYRK1A/B inhibition. Indeed, CC-401 inhibited DYRK1A-dependent phosphorylation/stabilization of the ?-cell replication-inhibitor p27Kip1. Additionally, CC-401 increased expression of numerous replication-promoting genes normally suppressed by the dimerization partner, RB-like, E2F and multi-vulval class B (DREAM) complex, which depends upon DYRK1A/B activity for integrity, including MYBL2 and FOXM1. In summary, we present a compendium of compounds as a valuable resource for manipulating the signaling pathways that control ?-cell replication and leverage a novel DYRK1A/B inhibitor (CC-401) to expand our understanding of the molecular pathways that control ?-cell growth.

    View details for DOI 10.1210/en.2018-00083

    View details for PubMedID 29514186

  • Platinum-Catalyzed alpha,beta-Unsaturated Carbene Formation in the Formal Syntheses of Frondosin B and Liphagal ORGANIC LETTERS Huynh, K. Q., Seizert, C. A., Ozumerzifon, T. J., Allegretti, P. A., Ferreira, E. M. 2017; 19 (1): 294-297

    Abstract

    Formal syntheses of tetracyclic terpenoids frondosin B and liphagal are described. Both synthetic routes rely on the use of platinum-catalyzed ?,?-unsaturated carbene formation for the key C-C bond forming transformations. The successful route toward frondosin B utilizes a formal (4 + 3) cycloaddition, while the liphagal synthesis features the vinylogous addition of an enol nucleophile as a key step. Both synthetic routes are discussed, revealing insights into structural requirements in the catalytic ?,?-unsaturated carbene reaction manifold.

    View details for DOI 10.1021/acs.orglett.6b03682

    View details for Web of Science ID 000391781600075

    View details for PubMedID 27997203

    View details for PubMedCentralID PMC5369019

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