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Archive - Nov 1, 2015

New Drug Inhibits WEE1 Protein and Kills Cancer Cells Expressing Mutated SETD2 Gene, Often Found in Kidney Cancers and Sometimes Childhood Brain Tumors; Test to ID SETD2 Mutated Tumors Developed, Immediate Diagnostic Use Possible

In a November 1, 2015 press release from the University of Oxford, it was announced that Oxford scientists have identified an Achilles heel of certain cancer cells, namely mutations in a gene called SETD2. Their findings will be presented to the National Cancer Research Institute conference in Liverpool, UK, on Monday, November 2, 2015. It is well known that mutations drive cancer cell growth and resistance to treatment. However, these mutations can also become a weak point for a tumor. The Oxford research team found that this is the case for cancer cells with mutations in a key cancer gene called SETD2. Study author Dr. Timothy Humphrey said “Mutations in SETD2 are frequently found in kidney cancer and some childhood brain tumors, so we were excited when we discovered that a new drug we were studying specifically killed cancer cells with this mutation.” The normal human SETD2 gene codes for a histone demthyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active chromatin. This protein also contains a novel transcriptional activation domain and has been found associated with hyper-phosphorylated RNA polymerase II. The SETD2 gene is located on the short arm of chromosome 3 and has been shown to play a tumour suppressor role in human cancer The Liverpool presentation will discuss how Dr. Humphrey and his team showed that cancer cells with a mutated SETD2 gene are killed by a drug called AZD1775 that inhibits a protein called WEE1 (image). The WEE1 protein was first discovered by British Nobel Prize winner Sir Paul Nurse.

Scientists ID Over 3,000 Long Non-Coding RNA (lncRNA) Genes That May Offer Insights into Development of Human Immune System; Findings Provide “Huge and Unique Resource for the Whole Immunology Community”

Scientists at the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have discovered more than 3,000 previously unknown genes in a poorly understood part of the genome. These genes, found in rare cells in the bone marrow and thymus, give scientists a new understanding of how the human immune system develops. The findings were published online on October 26, 2015 in Nature Immunology. The article is titled “Long Non-Coding RNA Profiling of Human Lymphoid Progenitor Cells Reveals Transcriptional Divergence of B Cell and T Cell Lineages.” “The genes we found are called long non-coding RNAs, or lncRNAs,” said Gay Crooks (photo), M.D., Co-Director of the UCLA Broad Stem Cell Research Center, a member of the UCLA Jonsson Comprehensive Cancer Center, and co-senior author of the Nature Immunology study. “They make up much of what we used to think of as the ‘dark matter’ of our genome because, unlike the better-known messenger RNA genes, they do not produce [code for the production of] proteins. The function of lncRNAs is not well-known, but it is becoming increasingly apparent that they are not inert; they have a critical role in controlling how other genes function,” she said. Researchers used the UCLA Broad Stem Cell Research Center’s state-of-the-art cell isolation and genetic sequencing technologies, and sophisticated bioinformatics to identify the elusive lncRNA genes. The team was led by Dr. Crooks, co-senior author Chintan Parekh, M.D., (now with Children’s Hospital Los Angeles), and first author David Casero, Ph.D. The team isolated rare blood-forming stem cells and progenitor cells from adult human bone marrow and thymus gland tissue. They then separated the genetic information in the cells using sequencing technology. Lastly, Dr.

Initiative to Harness Earth's Microbiomes Put Forward by 48-Member US Consortium Including Prominent Scientists from Harvard Medical School, Boston Children’s Hospital, & California NanoSystems Institute

A consortium of 48 scientists from 50 institutions in the United States – and including Pamela Silver, Ph.D., a Core Faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard University - is calling for a “Unified Microbiome Initiative” that would span national cross-institutional and cross-governmental agency support. The group, called the Unified Microbiome Initiative Consortium (UMIC), envisions that a coordinated effort would drive forward cutting-edge microbiome research, enabling breakthrough advances across medicine, ecosystem management, sustainable energy, and production of commodities. Their proposal was published in an open-access Policy Forum article in the October 30, 2015 issue of Science. The article is titled “A Unified Initiative to Harness Earth's Microbiomes.” Microbial life forms, including viruses, bacteria, and fungi, are the most diverse and abundant organisms on earth. They have shaped our evolutionary origins for billions of years and continue to have widespread impact on the planet, its environment, and the species inhabiting it. Together, they make up “microbiomes” that influence each other, the environment, and the host organisms that these microbial communities thrive in. The UMIC foresees that the microbiomes populating our planet and its many diverse species and environments could be leveraged through genetic engineering for applications that improve the greater good, and that many milestones could be reached on this front within ten years. "Microbes are everywhere. Therefore understanding microbiomes, whether they be the ones that live in and on our bodies or the ones in the environment, is essential to understanding life," said Dr. Silver.

Plasma miRNA Biomarkers Identified for Schizophrenia; May Enable First Objective Diagnostic Test for This Disorder; Accompanying Editorial Notes Possible Role of miRNA-Protective Exosomes

Researchers in China have shown that the up-regulation of two microRNAs (miR-130b and miR-193a-3p) in plasma is a state-independent biomarker for schizophrenia and the scientists suggest that these two miRNAs could be used to develop a diagnostic tool for schizophrenia. The new results were published in the November 1, 2015 issue of the American Journal of Psychiatry in an article titled “Detection of Circulating miRNA Levels in Schizophrenia.” The authors, from the Peking University Institute of Mental Health; and collaborating institutions in China, noted that schizophrenia is one of the most common severe mental disorders, with a lifetime risk of 1% in the population worldwide. Today, the diagnosis of schizophrenia remains symptom-based, relying mainly on self-reports from patients, mental state examination, and clinical interviews, and lacking objective laboratory tests. Such a diagnostic strategy can sometimes lead to misdiagnosis and has been widely criticized, the authors said. To remedy this “embarrassing state of affairs,” a set of biomarkers has previously (2012) been proposed based on physical and biological tests. The authors stated, however, that while “numerous studies have reported that circulating miRNA levels are highly associated with various diseases in humans, such as diabetes, cancer, and immunological diseases, there has been no systematic research on circulating miRNAs in psychiatric diseases.” The motivation for the current study was to pursue such an effort by determining whether circulating miRNA can serve as a diagnostic biomarker for schizophrenia. Briefly, the details of the new Chines work are as follows.