PROGRAM 3: Integration of homeostatic and dynamic signals: genotoxic stress responses. Eukaryotic organisms have evolved multiple mechanisms of sensing DNA damage and genotoxic stress. The resulting signals are integrated though a regulatory network that also samples the metabolic health of the cell by involving mitochondrial signaling mediators. By integrating dynamic genotoxic response signals and homeostatic regulatory networks, cells determine a variety of different responses, including the decision to undergo cell death via apoptotic or necroptotic pathways. In this Program, we will employ a systems approach to elucidating the mitochondria-dependent cell death program that is conserved from yeast to mammalian cells.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1-CBCB-2)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
La Jolla
United States
Zip Code
Saito, Rintaro; Rocanin-Arjo, Anaïs; You, Young-Hyun et al. (2016) Systems biology analysis reveals role of MDM2 in diabetic nephropathy. JCI Insight 1:e87877
Din, M Omar; Danino, Tal; Prindle, Arthur et al. (2016) Synchronized cycles of bacterial lysis for in vivo delivery. Nature 536:81-5
Gendron, Joshua M; Webb, Kristofor; Yang, Bing et al. (2016) Using the Ubiquitin-modified Proteome to Monitor Distinct and Spatially Restricted Protein Homeostasis Dysfunction. Mol Cell Proteomics 15:2576-93
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
Srivas, Rohith; Shen, John Paul; Yang, Chih Cheng et al. (2016) A Network of Conserved Synthetic Lethal Interactions for Exploration of Precision Cancer Therapy. Mol Cell 63:514-25
Engin, H Billur; Kreisberg, Jason F; Carter, Hannah (2016) Structure-Based Analysis Reveals Cancer Missense Mutations Target Protein Interaction Interfaces. PLoS One 11:e0152929
Steiner, Paul J; Williams, Ruth J; Hasty, Jeff et al. (2016) Criticality and Adaptivity in Enzymatic Networks. Biophys J 111:1078-87
Harper, J Wade; Bennett, Eric J (2016) Proteome complexity and the forces that drive proteome imbalance. Nature 537:328-38
Didovyk, Andriy; Borek, Bartłomiej; Hasty, Jeff et al. (2016) Orthogonal Modular Gene Repression in Escherichia coli Using Engineered CRISPR/Cas9. ACS Synth Biol 5:81-8
Yu, Michael Ku; Kramer, Michael; Dutkowski, Janusz et al. (2016) Translation of Genotype to Phenotype by a Hierarchy of Cell Subsystems. Cell Syst 2:77-88

Showing the most recent 10 out of 146 publications