The overall goal of the Signal Transduction Program (STP) is to elucidate the mechanisms that govern activation and repression of signaling cascades during normal development, neoplastic transformation and tumor progression. This goal is based on the premise that abnormalities in signal transduction are universal features of human cancer cells, and underiie virtually all aspects of the transformed phenotype. Members of the Signal Transduction Program currently pursue three major investigative areas: (1) kinases and phosphatases that are important in tumor development and known to undergo changes in human tumors;(2) ubiquitin ligases and ubiquitin-like proteins that play important roles in cellular pathways that are deregulated during tumor development and progression;and (3) an emerging theme of altered metabolic signaling in cancer. The Signal Transduction Program was established in 2001, and has been greatly strengthened since the last renewal by recruitment of new faculty members with expertise that complements the interests of the original faculty members. Of the 16 current members, 11 members have been recruited since 2003. Among them is Dr. Ze'ev Ronai, who was recruited as new Program Leader for the Signal Transduction Program in 2004. The Program is highly collaborative and interactive as evidenced by joint laboratory meetings, joint mentoring of graduate students and postdoctoral fellows, joint mentoring program for young faculty, monthly postdoctoral fellow presentations, monthly faculty meetings, monthly interest group (ubiquitin, ER stress) meetings, the annual postdoctoral retreat, and several Program Project grant initiatives underway. As a result of these activities, Program members lead or participate in 4 POl grants (2 from NCI), in multiple shared federal and state grants, and multiple co-authored publications. The high productivity of the Program during the past grant period is further documented by 21 ROI grants (7 from NCI) held by the Program members;by the current total annual grant funding of $14.5MM ($8.2MM direct);by 392 publications since last review, and by 65 Program publications in 2008, which represent 11% of intra- and 31% of interprogrammatic collaborations, respectively.

Public Health Relevance

Abnormalities in signal transduction underiie virtually all aspects of the transformed phenotype. Understanding these processes is expected to produce insights into the development and progression of cancer, to facilitate the development of tools to better probe the biology of cancer, and, ultimately, serve as guidance for therapeutics development.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA030199-33
Application #
8669927
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
33
Fiscal Year
2014
Total Cost
$108,876
Indirect Cost
$100,216
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Lechtenberg, Bernhard C; Rajput, Akhil; Sanishvili, Ruslan et al. (2016) Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation. Nature 529:546-50
Zhong, Zhenyu; Umemura, Atsushi; Sanchez-Lopez, Elsa et al. (2016) NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria. Cell 164:896-910
Olson, Erika J; Lechtenberg, Bernhard C; Zhao, Chunxia et al. (2016) Modifications of a Nanomolar Cyclic Peptide Antagonist for the EphA4 Receptor To Achieve High Plasma Stability. ACS Med Chem Lett 7:841-6
Tinoco, Roberto; Carrette, Florent; Barraza, Monique L et al. (2016) PSGL-1 Is an Immune Checkpoint Regulator that Promotes T Cell Exhaustion. Immunity 44:1190-203
Zhao, Wei; Mazar, Joseph; Lee, Bongyong et al. (2016) The Long Noncoding RNA SPRIGHTLY Regulates Cell Proliferation in Primary Human Melanocytes. J Invest Dermatol 136:819-28
Singec, Ilyas; Crain, Andrew M; Hou, Junjie et al. (2016) Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling. Stem Cell Reports 7:527-42
McQuary, Philip R; Liao, Chen-Yu; Chang, Jessica T et al. (2016) C. elegans S6K Mutants Require a Creatine-Kinase-like Effector for Lifespan Extension. Cell Rep 14:2059-67
Moscat, Jorge; Karin, Michael; Diaz-Meco, Maria T (2016) p62 in Cancer: Signaling Adaptor Beyond Autophagy. Cell 167:606-609
Miletic, Ana V; Jellusova, Julia; Cato, Matthew H et al. (2016) Essential Role for Survivin in the Proliferative Expansion of Progenitor and Mature B Cells. J Immunol 196:2195-204
Koh, Mei Yee; Gagea, Mihai; Sargis, Timothy et al. (2016) A new HIF-1α/RANTES-driven pathway to hepatocellular carcinoma mediated by germline haploinsufficiency of SART1/HAF in mice. Hepatology 63:1576-91

Showing the most recent 10 out of 425 publications