Daily Archives: September 26, 2014

PUBLIC RELEASE DATE:

25-Sep-2014

Contact: Leslie Ridgeway lridgewa@usc.edu 323-442-2823 University of Southern California - Health Sciences

LOS ANGELES Keck Medicine of USC scientists have discovered new clues about a drug instrumental in treating a certain blood cancer that may provide important targets for researchers searching for cures.

The team investigated whether demethylation of gene bodies induced by the drug 5-Aza-CdR (decitabine), which is used to treat pre-leukemia, could alter gene expression and possibly be a therapeutic target in cancer.

"When we put the drug in cancer cells, we found it not only reactivated some tumor suppressor genes, but it down-regulated the overexpressed oncogene (cancer gene)," said Gangning Liang, Ph.D., associate professor of research, Keck School of Medicine of USC Department of Urology, who is corresponding author on the research. "Overexpression is what turns cancer 'on.' The mechanism by which the drug accomplishes this dual action is by removing DNA methylation in the gene body, which we didn't expect."

DNA methylation is an epigenetic signaling tool used by cells use to turn genes off. DNA methylation is an important component in many cellular processes, including embryonic development. Mistakes in methylation are linked to several human diseases, including cancer.

The research builds upon past research by Peter Jones, Ph.D., D.Sc., former director of the USC Norris Comprehensive Cancer Center, Distinguished Professor of Urology and Biochemistry & Molecular Biology, and now director of research at the Van Andel Institute.

"The beginnings of epigenetic therapy, which is now the standard of care for myelodysplastic syndrome, can be traced back to the discovery of the DNA demethylating effects of 5-Azacytidine at Children's Hospital Los Angeles in 1980," Jones said. "Since that time we have always assumed that the drugs act by switching genes on, thus reapplying the 'brakes' to cancer cells. In this paper we show that they may also work by turning down the levels of genes, which have become overexpressed in cancer. In other words, they may also decrease the 'gasoline' and this two pronged mechanism, which was entirely unexpected, may help explain why patients respond to epigenetic therapy."

The research, "Gene body methylation can alter gene expression and is a therapeutic target in cancer," was published online Sept. 25, 2014 in Cancer Cell.

Continued here:
USC researchers discover dual purpose of cancer drug in regulating expression of genes

PUBLIC RELEASE DATE:

25-Sep-2014

Contact: Sandy Van sandy@prpacific.com 808-526-1708 Cedars-Sinai Medical Center @cedarssinai

LOS ANGELES (Sept. 25, 2014) Investigators at the Cedars-Sinai Board of Governors Regenerative Medicine Institute have received a grant from the National Institutes of Health to participate in a consortium taking the study of motor neuron disorders such as Lou Gehrig's disease and spinal muscular atrophy to a new, comprehensive perspective.

"We will be working as part of an NIH initiative to create databases of disease 'signatures' by generating and analyzing thousands of data points. Scientists often focus on very small things, such as a single signaling pathway in cells or a single gene or protein that is involved in some way with disease development, but identifying and correcting one component rarely leads to a cure. This is especially true in the brain because its networks are very complex," said Clive Svendsen, PhD, professor and director of the Board of Governors Regenerative Medicine Institute, principal investigator of Cedars-Sinai's part of the study.

Svendsen, the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine, compares this shift in perspective to the way meteorologists began predicting weather years ago viewing global trends and collecting vast amounts of data to create a forecast for a specific place and time.

The grant is part of an NIH initiative called the Library of Integrated Network-based Cellular Signatures, or LINCS, program, which aims to develop a "library" of molecular signatures that describes how different cells respond to proteins, genes, chemicals essentially anything that may come in contact with or change the cell or its activity.

Cedars-Sinai is a member of a group, NeuroLINCS, studying motor neuron disorders, which include Lou Gehrig's disease, also known as amyotrophic lateral sclerosis, or ALS, and spinal muscular atrophy. The NeuroLINCS study will be coordinated by researchers at the University of California, Irvine, with additional collaborators at the Gladstone Institutes at the University of California, San Francisco, Johns Hopkins University and the Broad Institute.

NeuroLINCS is one of six consortiums recently funded through NIH's LINCS program to study diabetes, cancers and other diseases using cell lines and specialized stem cells called induced pluripotent stem cells. Derived from a patient's own skin samples and "sent back in time" through genetic manipulation to an embryonic state, these cells can be made into any cell of the human body.

The Board of Governors Regenerative Medicine Institute, which has developed a national reputation for the quality of its induced pluripotent stem cells, was asked to provide the stem cells for all of the consortiums. The cells are produced in the Regenerative Medicine Institute's Induced Pluripotent Stem Cell Core Facility, directed by Dhruv Sareen, PhD, assistant professor of biomedical sciences and faculty research scientist with the Department of Biomedical Sciences.

Read the rest here:
With NIH grant, Cedars-Sinai helps bring big data to neuro disease research