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

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA062203-20
Application #
9208767
Study Section
Subcommittee A - Cancer Centers (NCI-A)
Project Start
Project End
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
20
Fiscal Year
2017
Total Cost
$8,324
Indirect Cost
$2,936
Name
University of California Irvine
Department
Type
Domestic Higher Education
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92617
Konstorum, Anna; Lowengrub, John S (2018) Activation of the HGF/c-Met axis in the tumor microenvironment: A multispecies model. J Theor Biol 439:86-99
Yan, Huaming; Konstorum, Anna; Lowengrub, John S (2018) Three-Dimensional Spatiotemporal Modeling of Colon Cancer Organoids Reveals that Multimodal Control of Stem Cell Self-Renewal is a Critical Determinant of Size and Shape in Early Stages of Tumor Growth. Bull Math Biol 80:1404-1433
Wang, Xiaolin; Zhao, Da; Phan, Duc T T et al. (2018) A hydrostatic pressure-driven passive micropump enhanced with siphon-based autofill function. Lab Chip 18:2167-2177
Flather, Dylan; Nguyen, Joseph H C; Semler, Bert L et al. (2018) Exploitation of nuclear functions by human rhinovirus, a cytoplasmic RNA virus. PLoS Pathog 14:e1007277
Hou, Jue; Williams, Joshua; Botvinick, Elliot L et al. (2018) Visualization of Breast Cancer Metabolism Using Multimodal Nonlinear Optical Microscopy of Cellular Lipids and Redox State. Cancer Res 78:2503-2512
George, Andrée S; Cox, Clayton E; Desai, Prerak et al. (2018) Interactions of Salmonella enterica Serovar Typhimurium and Pectobacterium carotovorum within a Tomato Soft Rot. Appl Environ Microbiol 84:
Reidling, Jack C; Relaño-Ginés, Aroa; Holley, Sandra M et al. (2018) Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice. Stem Cell Reports 10:58-72
Lagarrigue, Frederic; Gingras, Alexandre R; Paul, David S et al. (2018) Rap1 binding to the talin 1 F0 domain makes a minimal contribution to murine platelet GPIIb-IIIa activation. Blood Adv 2:2358-2368
Santos, Rommel A; Fuertes, Ariel J C; Short, Ginger et al. (2018) DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring. Neural Dev 13:22
Ullmer, Wendy; Semler, Bert L (2018) Direct and Indirect Effects on Viral Translation and RNA Replication Are Required for AUF1 Restriction of Enterovirus Infections in Human Cells. MBio 9:

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