New Biomarkers Might Help Personalize Metastatic Colorectal Cancer Treatment

Low levels of two genes predicts positive response to chemotherapy and longer survival times —

Metastatic colorectal cancer patients tend to live longer when they respond to the first line of chemotherapy their doctors recommend. To better predict how patients will respond to chemotherapy drugs before they begin treatment, researchers at University of California, San Diego School of Medicine conducted a proof-of-principle study with a small group of metastatic colorectal cancer patients. The results, published June 17 in PLOS ONE, revealed two genes that could help physicians make more informed treatment decisions for patients with this disease. …Read the full story from the UC San Diego Newsroom

Paul Fanta, MD, MS

Paul Fanta, MD, MS

Senior author of the study is Department of Medicine oncologist Paul Fanta, MD, MS, Health Sciences associate clinical professor in the Division of Hematology-Oncology. Dr. Fanta is a researcher in the Solid Tumor Therapeutics Program at the UC San Diego Moores Cancer Center.

Read the article in PLOS ONE (Open Access)

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

“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:

Potential Nutritional Therapy for Childhood Neurodegenerative Disease

Researchers at the University of California, San Diego School of Medicine have identified the gene mutation responsible for a particularly severe form of pontocerebellar hypoplasia, a currently incurable neurodegenerative disease affecting children. Based on results in cultured cells, they are hopeful that a nutritional supplement may one day be able to prevent or reverse the condition…. Read the full story from the UCSD Newsroom


Robert K. Naviaux, MD, PhD, is a coauthor of the study. He is professor of medicine in the Division of Medical Genetics and professor in the departments of pediatrics and pathology.

Naviaux leads a medical genetics research laboratory whose two major areas of study are the mitochondrial mechanisms of disease and development and evolutionary systems biology and marine metagenomics. He is founder and co-director of the UC San Diego Mitochondrial and Metabolic Disease Center.

Citation for the report:  Naiara Akizu, Vincent Cantagrel, Jana Schroth, Na Cai, Keith Vaux, Douglas McCloskey, Robert K. Naviaux, Jeremy Van Vleet, Ali G. Fenstermaker, Jennifer L. Silhavy, Judith S. Scheliga, Keiko Toyama, Hiroko Morisaki, Fatma M. Sonmez, Figen Celep, Azza Oraby, Maha S. Zaki, Raidah Al-Baradie, Eissa A. Faqeih, Mohammed A.M. Saleh, Emily Spencer, Rasim Ozgur Rosti, Eric Scott, Elizabeth Nickerson, Stacey Gabriel, Takayuki Morisaki, Edward W. Holmes, Joseph G. Gleeson. AMPD2 Regulates GTP Synthesis and Is Mutated in a Potentially Treatable Neurodegenerative Brainstem Disorder. Cell, Volume 154, Issue 3, 1 August 2013, Pages 505–517 http://dx.doi.org/10.1016/j.cell.2013.07.005  Read the report

Related Stories:

Drug Treatment Corrects Autism Symptoms in Mouse Model – March 14, 2013

$5.9 Million Grant to UC San Diego for Paradigm-Shifting Diabetes Research – October 3, 2011

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

Biomarking Time

Methylome modifications offer new measure of our “biological” age

Women live longer than men. Individuals can appear or feel years younger – or older – than their chronological age. Diseases can affect our aging process. When it comes to biology, our clocks clearly tick differently.

In a new study, researchers at the University of California, San Diego School of Medicine, with colleagues elsewhere, describe markers and a model that quantify how aging occurs at the level of genes and molecules, providing not just a more precise way to determine how old someone is, but also perhaps anticipate or treat ailments and diseases that come with the passage of time. … Read the full story from the UCSD Newsroom


Trey Ideker, PhDTrey Ideker, PhD, is co-senior author of the study report. He is professor of medicine and chief of the Division of Medical Genetics, professor of bioengineering and faculty investigator in the UCSD Institute for Genomic Medicine.The overall goal of Ideker’s work is to map and model molecular networks of cellular processes in health and disease, particularly in cancer and the response to genotoxic stress.

Coauthors of the study report include Rob DeConde, a graduate student in Ideker’s laboratory.

Read the abstract of the study report in PubMed

Citation: Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, Fan J-B, Gao Y, Deconde R, Chen M, Rajapakse I, Friend S, Ideker T, Zhang K: Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Molecular cell doi:10.1016/j.molcel.2012.10.016. PMID: 23177740

Enzyme Offers New Therapeutic Target for Cancer Drugs

Researchers at the University of California, San Diego School of Medicine have uncovered a new signal transduction pathway specifically devoted to the regulation of alternative RNA splicing, a process that allows a single gene to produce or code multiple types of protein variants. The discovery, published in the June 27, 2012 issue of Molecular Cell, suggests the new pathway might be a fruitful target for new cancer drugs. … Read the full story from the UCSD Newsroom


ALTDepartment of Medicine faculty co-author M. Geoffrey Rosenfeld, MD, is distinguished professor of medicine and an investigator in the Howard Hughes Medical Institute.

Read the article summary in Molecular Cell.

Article Citation:
The Akt-SRPK-SR Axis Constitutes a Major Pathway in Transducing EGF Signaling to Regulate Alternative Splicing in the Nucleus
Zhihong Zhou, Jinsong Qiu, Wen Liu, Yu Zhou, Ryan M. Plocinik, Hairi Li, Qidong Hu, Gourisanker Ghosh, Joseph A. Adams, Michael G. Rosenfeld, and Xiang-Dong Fu
10.1016/j.molcel.2012.05.014.

Dr. Rosenfeld’s laboratory

How Infectious Disease May Have Shaped Human Origins

Inactivation of two genes may have allowed escape from bacterial pathogens, researchers say

Roughly 100,000 years ago, human evolution reached a mysterious bottleneck: Our ancestors had been reduced to perhaps five to ten thousand individuals living in Africa. In time, “behaviorally modern” humans would emerge from this population, expanding dramatically in both number and range, and replacing all other co-existing evolutionary cousins, such as the Neanderthals. … Read the full story from the UCSD Newsroom

Insulin Resistance, Inflammation and a Muscle-Saving Protein

In the online May 2 issue of the journal Cell Metabolism, researchers at the University of California, San Diego School of Medicine publish three distinct articles exploring:

  • the complex interactions of lipids and inflammation in insulin resistance
  • the roles of omega 3 fatty acids and a particular gene in fighting inflammation
  • how elevated levels of a particular protein might delay the muscle-destroying effects of amyotrophic lateral sclerosis.

Type 2 diabetes has reached epidemic proportions around the world … Read the full story from the UCSD Newsroom


Dr. Jerrold Olefsky
Dr. Jerrold Olefsky coauthored two of the three articles published:

  • Perspective article: Inflammation and Lipid Signaling in the Etiology of Insulin Resistance – Free full text
  • Omega 3 Fatty Acids and GPR120 – Article summary

Dr. Olefsky is Associate Dean for Scientific Affairs, UC San Diego Health Sciences; and Distinguished Professor of Medicine in the Division of Endocrinology and Metabolism.

New Drug Target Improves Memory in Mouse Model of Alzheimer’s Disease

Researchers at the University of California, San Diego, the Medical University of South Carolina, the University of Cincinnati, and American Life Science Pharmaceuticals of San Diego have validated the protease cathepsin B (CatB) as a target for improving memory deficits and reducing the pathology of Alzheimer’s disease (AD) … Read the full story from the UCSD Newsroom

Read the abstract of the study report in the Journal of Alzheimer’s Disease

Dr. Vivian Hook
Study co-investigator Vivian Y. H. Hook, PhD, is professor in the departments of neurosciences and pharmacology and professor of medicine in the Division of Nephrology-Hypertension.

Related story: Potential New Drug Candidate Found for Alzheimer’s Disease, May 31, 2011