Researchers ID Cancer Gene-Drug Combinations Ripe for Precision Medicine

Yeast, human cells and bioinformatics help develop one-two punch approach to personalized cancer therapy —

In an effort to expand the number of cancer gene mutations that can be specifically targeted with personalized therapies, researchers at University of California San Diego School of Medicine and Moores Cancer Center looked for combinations of mutated genes and drugs that together kill cancer cells. Such combinations are expected to kill cancer cells, which have mutations, but not healthy cells, which do not. The study, published July 21 in Molecular Cell, uncovered 172 new combinations that could form the basis for future cancer therapies.

“Oncologists here at Moores Cancer Center at UC San Diego Health and elsewhere can often personalize cancer therapy based on an individual patient’s unique cancer mutations,” said senior author Trey Ideker, PhD, … Read the Full Story by Heather Buschman from the UC San Diego Newsroom


Trey Ideker, PhD

Trey Ideker, PhD

Senior author of the study report in Molecular Cell is Trey Ideker, PhD, Professor of Medicine in the Division of Medical Genetics and Professor of Bioengineering at UC San Diego.

HIV Infection Prematurely Ages People by an Average of Five Years

Epigenetic changes also associated with 19 percent increased risk of mortality —

Thanks to combination antiretroviral therapies, many people with HIV can expect to live decades after being infected. Yet doctors have observed these patients often show signs of premature aging. Researchers at University of California San Diego School of Medicine and the University of Nebraska Medical Center have applied a highly accurate biomarker to measure just how much HIV infection ages people at the cellular level — an average of almost five years.

The study is published April 21 in Molecular Cell. … Read the Full Story from the UC San Diego Newsroom


Trey Ideker, PhD

Trey Ideker, PhD

Trey Ideker, PhD, Professor of Medicine and Professor of Bioengineering, is co-corresponding author of the study report in Molecular Cell (article access for UC San Diego only).

Other Department of Medicine authors include Andrew M. Gross, Philipp A. Jaeger, Jason F. Kreisberg and Katherine Licon.

UC San Diego, UC San Francisco Launch New Cancer Cell Mapping Initiative

Researchers from the University of California, San Diego School of Medicine and University of California, San Francisco, with support from a diverse team of collaborators, have launched an ambitious new project – dubbed the Cancer Cell Map Initiative or CCMI – to determine how all of the components of a cancer cell interact.

“We’re going to draw the complete wiring diagram of a cancer cell,” said Nevan Krogan, PhD, director of the UC San Francisco division of QB3, a life science research institute and accelerator, an investigator at Gladstone Institutes and co-director of CCMI with Trey Ideker, PhD, chief of medical genetics in the UC San Diego Department of Medicine and founder of the UC San Diego Center for Computational Biology & Bioinformatics. … Read the full story from the UC San Diego Newsroom

 


Trey Ideker, PhD

Trey Ideker, PhD

Trey Ideker, PhD, is professor of bioengineering and professor of medicine in the Division of Medical Genetics. He was recently named a fellow of the American Association for the Advancement of Science (AAAS).

Dr. Ideker’s Laboratory Website

Dr. Trey Ideker Named AAAS Fellow

Trey Ideker, PhD

Trey Ideker, PhD

Trey Ideker, PhD, professor of medicine in the Division of Medical Genetics and professor of bioengineering, is one of three UC San Diego faculty members to be named Fellow of the American Association for the Advancement of Science (AAAS) this year. …Read the full story from the UC San Diego Newsroom.

 

Tumor Suppressor Mutations Alone Don’t Explain Deadly Cancer

Biomarker for head and neck cancers identified

Although mutations in a gene dubbed “the guardian of the genome” are widely recognized as being associated with more aggressive forms of cancer, researchers at the University of California, San Diego School of Medicine have found evidence suggesting that the deleterious health effects of the mutated gene may in large part be due to other genetic abnormalities, at least in squamous cell head and neck cancers. … Read the full story from the UCSD Newsroom


Trey Ideker, PhD

Trey Ideker, PhD, professor and chief in the Division of Medical Genetics and professor of bioengineering, is one of the study’s co-senior authors.

Other Department of Medicine faculty authors include Hannah Carter, PhD, assistant professor; and Scott M. Lippman, MD, professor of medicine and director of the UC San Diego Moores Cancer Center.

Hannah Carter, PhD Dr. Scott M. Lippman

Richard D. Kolodner Elected to Institute of Medicine

University of California, San Diego School of Medicine researchers Joseph G. Gleeson, MD, Howard Hughes Medical Institute investigator and professor of neurosciences and pediatrics, and Richard D. Kolodner, PhD, professor of medicine and Ludwig Cancer Research scientist, have been named new members of the Institute of Medicine (IOM), considered among the highest honors in the fields of health and medicine. … Read the full story from the UC San Diego News Center


Dr. Richard KolodnerGeneticist and biochemist Richard D. Kolodner, PhD, is a distinguished professor in the departments of medicine (Division of Hematology-Oncology) and cellular and molecular medicine at UC San Diego.

Kolodner co-leads the Laboratory of Cancer Genetics in the San Diego branch of the Ludwig Institute for Cancer Research, which is located at UC San Diego.

At the UC San Diego Moores Cancer Center, he co-leads the Cancer Genomes and Networks research program with Trey Ideker, PhD, and is a member of the faculty of the Cancer Therapeutics Training (CT2) Program.

He is also a member of the Institute for Genomic Medicine and the Biomedical Sciences graduate program.

Kolodner was elected to the National Academy of Sciences in 2000 and the American Academy of Arts and Sciences in 2008. His election to the Institute of Medicine brings to 10 the number of Department of Medicine faculty members who are members of the institute.

See other UC San Diego news stories about Dr. Kolodner and his work.

“Wildly Heterogeneous Genes”

New approach subtypes cancers by shared genetic effects; a step toward personalized medicine

Cancer tumors almost never share the exact same genetic mutations, a fact that has confounded scientific efforts to better categorize cancer types and develop more targeted, effective treatments.

In a paper published in the September 15 advanced online edition of Nature Methods, researchers at the University of California, San Diego propose a new approach called network-based stratification (NBS), which identifies cancer subtypes not by the singular mutations of individual patients, but by how those mutations affect shared genetic networks or systems. … Read the full story from the UCSD Newsroom


Trey Ideker, PhDLead investigator in the study is Trey Ideker, PhD, professor of medicine and bioengineering and chief of the Division of Medical Genetics in the Department of Medicine.

Postdoctoral researcher Hannah K. Carter and hematology/oncology fellow John P. Shen are the other Department of Medicine coauthors.

Citation for the study report:  Matan Hofree, John P Shen, Hannah Carter, Andrew Gross, Trey Ideker. Network-based stratification of tumor mutations. Nature Methods (2013) doi:10.1038/nmeth.2651. |  Full text (UCSD only)

More Information:

Trey Ideker and Collaborators Release Cytoscape v3

Visualizing Complex Networks using New Cytoscape v3

On April 22, 2013, computational biologists and computer scientists at UC San Diego released version 3 of Cytoscape for general availability. Cytoscape is the leading open source visualization software platform supporting systems biology; it enables researchers to visualize molecular interaction networks and biological pathways and integrate them with annotations, gene expression profiles and other state and process data.

Cytoscape was developed in the early 2000s to meet the need for an analytical tool that would allow researchers to organize, view and interpret large-scale biological data in a unified conceptual framework.

Approximately 1,600 scientific papers have cited the software to date, with approximately 300-400 new papers each year.

The Cytoscape-generated image below is a visualization of a data set composed of molecular and genetic interactions within cells in the human body.

A Cytoscape visualization of a data set composed of molecular and genetic interactions within cells

Although it was originally designed for biological research, Cytoscape is now a general platform for complex network analysis and visualization, with additional applications in software engineering and the study of social networks.

Features new in Cytoscape v3 include edge bending and bundling visualizations (see image below), network annotations, advanced searching, node grouping and associated tutorials.

Cytoscape v3 also incorporates a new App Store, which enables Cytoscape users to access and use a large and growing pool of community-published visualization and analytics modules, thereby driving and enabling Cytoscape’s use both in biology and in diverse research environments.

The Cytoscape core application is open source and is distributed under a Library GNU Public License; each app carries an independent software license. Cytoscape’s open application programmer interface is based on Java™ technology.

Trey Ideker, PhDCytoscape project principal investigator Trey Ideker, PhD (left), said, “Cytoscape v3 is an important milestone in the support of systems biology, enabling deep insights into complex biologic relationships and processes.

“From a biological perspective, it will enable multiscale, dynamic, and ontological studies. From a systems perspective, it will enable collaborative workflows and better, more intensive use of existing and future computing resources.”

Ideker is professor of bioengineering and professor and chief of the Division of Medical Genetics in the Department of Medicine.Barry Demchak

The Ideker laboratory offers Cytoscape and a number of other software packages and tools for download. (http://idekerlab.ucsd.edu/software).

There are approximately 6,000 Cytoscape downloads each month, Ideker said.

Lead Cytoscape software architect Barry Demchak, PhD, pictured above right, said Cytoscape v3 represents a major redesign to boost the program’s performance, improve the user interface, and make the software more extensible and stable.

Cytoscape 3 visualization image.

New feature in Cytoscape 3: Automatic edge bundling consolidates multiple edges to de-clutter dense network views.

Cytoscape v3 is the culmination of two years’ work conducted by the National Institutes of Health-funded Cytoscape Consortium, which includes collaborators at UC San Diego, UC San Francisco, the University of Toronto, the Pasteur Institute, the Broad Institute, the Memorial Sloan-Kettering Cancer Center, and the Institute for Systems Biology.

Cytoscape is available for free download at http://cytoscape.org.

User support, education and new initiatives for Cytoscape are supported by the National Resource for Network Biology under award numbers P41 RR031228 and GM103504.   |  Watch Trey Ideker’s video introduction to NRNB

For further information, contact Barry Demchak (bdemchak@ucsd.edu or 858-452-8700) at UC San Diego.

More Information:

Other News Releases about Ideker’s Work

In Epigenomics, Location is Everything

Researchers exploit gene position to test “histone code”

In a novel use of gene knockout technology, researchers at the University of California, San Diego School of Medicine tested the same gene inserted into 90 different locations in a yeast chromosome – and discovered that while the inserted gene never altered its surrounding chromatin landscape, differences in that immediate landscape measurably affected gene activity. … Read the full story from the UCSD Newsroom


Trey Ideker, PhD

Led by Trey Ideker, PhD, researchers in the UCSD departments of bioengineering, biological sciences, and medicine collaborated in the study, which was published online this week in Cell Reports.

Ideker is professor of bioengineering and medicine and chief of the Division of Medical Genetics in the Department of Medicine.

The study investigators include Lorraine Pillus, PhD, professor and chair of the Section of Molecular Biology in the Division of Biological Sciences at UCSD, whose laboratory focuses on investigating chromosomal and chromatin effects on the expression of genes.

Citation for the study report: Chen M, Licon K, Otsuka R, Pillus L, and Ideker T. (2013) Decoupling Epigenetic and Genetic Effects through Systematic Analysis of Gene Position. 10.1016/j.celrep.2012.12.003   Read the article abstract.

Toward a New Model of the Cell

Everything You Always Wanted to Know About Genes

Turning vast amounts of genomic data into meaningful information about the cell is the great challenge of bioinformatics, with major implications for human biology and medicine. Researchers at the University of California, San Diego School of Medicine and colleagues have proposed a new method that creates a computational model of the cell from large networks of gene and protein interactions, discovering how genes and proteins connect to form higher-level cellular machinery. …Read the full story from the UCSD Newsroom


Trey Ideker, PhDThe new approach comes from the medical genetics laboratory of Trey Ideker, PhD, in the departments of bioengineering and medicine. Postdoctoral fellow Janusz Dutkowski, PhD, is lead author and Michael Kramer, PhD, a coauthor of the study report in Nature Biotechnology.

Ideker, senior author, is professor of bioengineering and medicine and chief of the Division of Medical Genetics in the Department of Medicine.

Citation for the report:  Dutkowski J, Kramer M, Surma MA, Balakrishnan R, Cherry JM, Krogan NJ, Ideker T. A gene ontology inferred from molecular networks. Nature Biotechnology (2012) doi:10.1038/nbt.2463. Published online 16 December 2012  Read the abstract