The Role of “Master Regulators” in Gene Mutations and Disease

Researchers identify key proteins that help establish cell function

Researchers at the University of California, San Diego School of Medicine have developed a new way to parse and understand how special proteins called “master regulators” read the genome, and consequently turn genes on and off. … Read the full story from the UC San Diego News Center


Christopher K. Glass, MD, PhDThe principal investigator of the reported study is Christopher K. Glass, MD, PhD, professor of medicine in the Division of Endocrinology & Metabolism and professor of cellular and molecular medicine at UC San Diego.

He is on the faculty of the UC San Diego Institute for Genomic Medicine.

Visit the Glass Laboratory website.

Related UC San Diego news stories:

Enhancer RNAs Alter Gene Expression

New class of molecules may be key emerging “enhancer therapy”

In a pair of distinct but complementary papers, researchers at the University of California, San Diego School of Medicine and colleagues illuminate the functional importance of a relatively new class of RNA molecules. The work, published online this week in the journal Nature, suggests modulation of “enhancer-directed RNAs” or “eRNAs” could provide a new way to alter gene expression in living cells, perhaps affecting the development or pathology of many diseases. … Read the full story from the UCSD Newsroom


Christopher K. Glass

Christopher K. Glass, MD, PhD

Drs. Christopher Glass (left) and M. Geoffrey Rosenfeld (at right below) are the principal investigators of the two studies reported in Nature.

M. Geoffrey Rosenfeld, MD

M. Geoffrey Rosenfeld, MD

Christopher Glass, MD, PhD, is professor of medicine and cellular and molecular medicine. M. Geoffrey Rosenfeld is professor of medicine and biology and is a Howard Hughes Medical Institute professor.

Both are members of the Division of Endocrinology & Metabolism in the Department of Medicine.

Citations for the study reports:

Glass report:

Michael T. Y. Lam, Han Cho, Hanna P. Lesch, David Gosselin, Sven Heinz, Yumiko Tanaka-Oishi, Christopher Benner, Minna U. Kaikkonen, Aneeza S. Kim, Mika Kosaka, Cindy Y. Lee, Andy Watt, Tamar R. Grossman, Michael G. Rosenfeld, Ronald M. Evans & Christopher K. Glass.  Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription.  Nature (2013) doi:10.1038/nature12209. Published online 02 June 2013.  |   Full Text  (UCSD only)

Rosenfeld report:

Wenbo Li, Dimple Notani, Qi Ma, Bogdan Tanasa, Esperanza Nunez, Aaron Yun Chen, Daria Merkurjev, Jie Zhang, Kenneth Ohgi, Xiaoyuan Song, Soohwan Oh, Hong-Sook Kim, Christopher K. Glass & Michael G. Rosenfeld. Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature (2013) doi:10.1038/nature12210. Published online 02 June 2013.  |  Full text  (UCSD only)

More Information:

Potential New Way to Suppress Tumor Growth Discovered

Researchers at the University of California, San Diego School of Medicine, with colleagues at the University of Rochester Medical Center, have identified a new mechanism that appears to suppress tumor growth, opening the possibility of developing a new class of anti-cancer drugs. … Read the full story from the UCSD Newsroom


Dr. Willis X. Li

Dr. Willis X. Li

Senior author of the study report in the Proceedings of the National Academy of Sciences is Willis X. Li, PhD, professor of medicine in the Division of Pulmonary & Critical Care Medicine and faculty member in the Biomedical Sciences graduate program.

Li’s UC San Diego Department of Medicine coauthors are postdoctoral fellow Pranabananda Dutta, PhD; pulmonary/critical care physician-scientist Jinghong Li, MD, PhD, and senior undergraduate student Jingtong Wang.

Coauthors Xiaoyu Hu, Amy Tsurumi and Hartmut Land are colleagues at the University of Rochester, where Li was a faculty member and researcher at the Wilmot Cancer Center before he joined the faculty at UC San Diego.

At the University of Rochester, LI received the 2008 Davey Memorial Award for Outstanding Cancer Research for his work in the cellular and molecular signaling in cancer development.

He is now principal investigator of an R01 research grant from the National Cancer Institute for the project, Epigenetic Tumor Induction by Heterochromatin Instability.

Citation for the study report:  

Xiaoyu Hu, Pranabananda Dutta, Amy Tsurumi, Jinghong Li, Jingtong Wang, Hartmut Land, and Willis X. Li. Unphosphorylated STAT5A stabilizes heterochromatin and suppresses tumor growth. PNAS 2013 ; published ahead of print June 3, 2013, doi:10.1073/pnas.1221243110  |  Abstract  |  Full text (PDF)

Drug Treatment Corrects Autism Symptoms in Mouse Model

An old drug gives hope for new treatment in autism

Autism results from abnormal cell communication. Testing a new theory, researchers at the University of California, San Diego School of Medicine have used a newly discovered function of an old drug to restore cell communications in a mouse model of autism, reversing symptoms of the devastating disorder.

The findings are published in the March 13, 2013 issue of the journal PLOS ONE. … Read the full story from the UCSD Newsroom


First author of the study report is Robert K. Naviaux, MD, PhD, 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.

Naviaux earned his MD and PhD degrees at the Indiana University School of Medicine and received his advanced training in virology and molecular biology at the Salk Institute for Biological Studies. There, in the laboratory of Dr. Inder Verma, he conducted investigations in gene therapy and retrovirus biology.

Other Department of Medicine authors of the report are Laura L. Dugan, MD, who is chief of the Division of Geriatrics and Larry L. Hillblom Chair in Geriatric Medicine; research associates Lin Wang and Qingbo Tang; and Mihael Rogac.

Citation for the report:  Naviaux RK, Zolkipli Z, Wang L, Nakayama T, Naviaux JC, et al. (2013) Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model. PLoS ONE 8(3): e57380. doi:10.1371/journal.pone.0057380  |  Read the report

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.

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

Plasticity of Hormonal Response Permits Rapid Gene Expression Reprogramming

Gene expression reprogramming may allow cancer cell growth as well as normal differentiation

Gene expression is the process of converting the genetic information encoded in DNA into a final gene product such as a protein or any of several types of RNA. Scientists have long thought that the gene programs regulated by different physiological processes throughout the body are robustly pre-determined and relatively fixed for every specialized cell. But a new study by researchers from the University of California, San Diego School of Medicine reveals the unsuspected plasticity of some of these gene expression programs. … Read the full story from the UCSD Newsroom

M. Geoffrey Rosenfeld, MD

Co-principal investigator of the study is Dr. M. Geoffrey Rosenfeld (pictured at left). M. Geoffrey Rosenfeld, MD, is Professor of Medicine in the Division of Endocrinology and Metabolism and Howard Hughes Medical Institute investigator.

Department of Medicine coauthor Christopher K. Glass, MD, PhD, is Professor of Medicine in the Division of Endocrinology and Metabolism and Professor of Cellular and Molecular Medicine.

Read the published study in Nature (free full text).