- Systems, Pathways & Targets (SPT) The Systems, Pathways & Targets (SPT) Program is a newly formed program (created in 2011) that integrates cancer-focused members from two prior programs with new members who have expertise in the systems biology of cancer. SPT members focus on cellular signaling, tissue morphogenesis and computational modeling/bioinformatics. The overarching goal of this program is to identify key proteins or points of crosstalk for therapeutic intervention. To achieve this goal, three aims are proposed: 1) Identify key targets in signaling pathways, developmental pathways, and metabolic programs that are relevant to cancer initiation, progression, and therapeutic resistance, 2) Develop multi-disciplinary teams to study tumor heterogeneity and microenvironment/cellular interactions, 3) Diversify multi-disciplinary approaches to develop new therapeutic strategies. SPT members include cell biologists, immunologists, geneticists, developmental biologists, computational scientists, and clinicians. Dr. David Fruman and Dr. John Lowengrub direct the program as co- leaders. Their expertise in cellular signaling and drug development (Fruman) and systems biology of the tumor microenvironment (Lowengrub) embody the scientific breadth of basic research in the program, their partnering with basic and physician scientist members demonstrates the collaborative nature of SPT. Since the last renewal, exciting progress has been made in the identification of new targets in cancer cells and the development of small lead compounds against those targets. The first subset of these molecules are making their way to the bedside in the form of pre-clinical tests and clinical trials. Strategic partnering with members of the Chemical and Structural Biology (CSB) program has led to the synthesis of a second subset of molecules for evaluation in pre-clinical assays. In addition, SPT members have collaborated with bioengineers in the Onco-Imaging and Biotechnology (OIB) program for the development of new tools for cancer research. New collaborations with members of the Cancer Prevention, Outcomes and Survivorship (CPOS) program show promise in identifying and addressing issues in the catchment area of the cancer center. In the future, the SPT program leadership will continue to leverage the unique breadth and synergy among its members to build collaborative teams that tackle long-standing problems using bold and innovative approaches. Membership: 55 Members from 17 Departments Funding: $2,731,793 NCI (Totals); $9,767,626 Other Peer-Reviewed (Totals) Publications: 588 Publications, 15% Inter-programmatic; 12% Intra-programmatic

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National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee I - Transistion to Independence (NCI)
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University of California Irvine
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Charney, Rebekah M; Forouzmand, Elmira; Cho, Jin Sun et al. (2017) Foxh1 Occupies cis-Regulatory Modules Prior to Dynamic Transcription Factor Interactions Controlling the Mesendoderm Gene Program. Dev Cell 40:595-607.e4
HD iPSC Consortium (2017) Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice. Nat Neurosci 20:648-660
McCracken, A N; McMonigle, R J; Tessier, J et al. (2017) Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation. Leukemia 31:669-677
Barton, James C; Chen, Wen-Pin; Emond, Mary J et al. (2017) GNPAT p.D519G is independently associated with markedly increased iron stores in HFE p.C282Y homozygotes. Blood Cells Mol Dis 63:15-20
Yan, Huaming; Romero-Lopez, Monica; Frieboes, Hermann B et al. (2017) Multiscale Modeling of Glioblastoma Suggests that the Partial Disruption of Vessel/Cancer Stem Cell Crosstalk Can Promote Tumor Regression Without Increasing Invasiveness. IEEE Trans Biomed Eng 64:538-548
Klempner, Samuel J; Mehta, Pareen; Schrock, Alexa B et al. (2017) Cis-oriented solvent-front EGFR G796S mutation in tissue and ctDNA in a patient progressing on osimertinib: a case report and review of the literature. Lung Cancer (Auckl) 8:241-247
Molino, Nicholas M; Neek, Medea; Tucker, Jo Anne et al. (2017) Display of DNA on Nanoparticles for Targeting Antigen Presenting Cells. ACS Biomater Sci Eng 3:496-501
Lomeli, Naomi; Di, Kaijun; Czerniawski, Jennifer et al. (2017) Cisplatin-induced mitochondrial dysfunction is associated with impaired cognitive function in rats. Free Radic Biol Med 102:274-286
Huang, Jason Y; Samarasena, Jason B; Tsujino, Takeshi et al. (2017) EUS-guided portal pressure gradient measurement with a simple novel device: a human pilot study. Gastrointest Endosc 85:996-1001
Elbir, Haitham; Sitlani, Parth; Bergström, Sven et al. (2017) Chromosome and Megaplasmid Sequences of Borrelia anserina (Sakharoff 1891), the Agent of Avian Spirochetosis and Type Species of the Genus. Genome Announc 5:

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