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Archive - Feb 2017


February 2nd

Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras

Cancer is a heterogeneous disease, with myriad distinct subtypes that differ in their genetic roots. As a result, cancers rely on varied pathways for survival--and respond differently to anticancer agents. The challenge for researchers is to precisely define those diverse pathways and pinpoint vulnerabilities that may serve as drug targets for new anti-cancer treatments. Investigators at the Whitehead Institute and the Broad Institute have taken an important step in tackling that challenge: They have succeeded in identifying the set of essential genes--those required for cellular proliferation and survival--in each of 14 human acute myeloid leukemia (AML) cell lines that had previously been characterized by genome sequencing. By combining their "gene essentiality map" with the existing genomic information, their study revealed liabilities in genetically defined subset of cancers that could be exploited for new therapies. The report on their work, appearing in the online edition of Cell on February 2, 2017, is entitled “Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras.” A major aspect of the study focuses on the genes and protein pathways connected to the Ras oncogene, the most commonly mutated oncogene in human cancers which plays a role in AML, as well as many other cancers. "For the most part, the mutant Ras protein itself has been considered to be 'undruggable,’" explain Tim Wang, the paper's first author and an MIT graduate student researcher at Whitehead Institute and the Broad Institute. "An alternative approach has been to find other genes that Ras-mutant cancers rely on with the hope that one of them may be druggable.

February 2nd

“In Vivo” Reprogramming Induces Signs of Telomere Rejuvenation

During the “in vivo” reprogramming process, cellular telomeres are extended due to an increase in endogenous telomerase. This is the main conclusion of a paper published online on February 2, 2017 in Stem Cell Reports by a team from the Spanish National Cancer Research Centre (CNIO). The open-access article is titled “Common Telomere Changes During In Vivo Reprogramming and Early Stages of Tumorigenesis.” The team’s observations show, for the first time, that the reprogramming of living tissue results in telomerase activation and telomere elongation; thus reversing one of the hallmarks of aging: i.e., the presence of short telomeres. "We have found that when you induce cell de-differentiation in an adult organism, the telomeres become longer, which is consistent with cellular rejuvenation,” explains Dr. María A. Blasco, head of the CNIO Telomeres and Telomerase Group and leader of this research. This lengthening of the telomeres is an unequivocal sign of cell rejuvenation, which has been quantified for the first time here in a living organism. Dr. Blasco and her colleagues have worked with the so-called "reprogrammable mice" - created by Dr. Manuel Serrano, also a CNIO researcher, whose group is also involved in this project. Broadly speaking, the cells of these transgenic animals carry the four Yamanaka factors (OSKM) whose expression is turned on when an antibiotic is administered. In doing so, the cells regress to an embryonic-like state, a condition known as known as pluripotency. In light of the importance of telomeres in tissue regeneration, aging, and cancer, the authors decided to analyze the changes that occur in these protective structures of the chromosomes during the “in vivo” reprogramming process, which leads to de-differentiation of the tissues.

University of Wisconsin Scientists Identify Two Proteins That May Aid Bone Growth to Restore Bone Tissue Lost to Disease or Injury

The prospect of regenerating bone lost to cancer or trauma is a step closer to the clinic as University of Wisconsin (UW)-Madison scientists have identified two proteins found in bone marrow as key regulators of the master cells responsible for making new bone. In a study published online on February 2, 2017 in the journal Stem Cell Reports, a team of UW-Madison scientists reports that the proteins govern the activity of mesenchymal stem cells -- precursor cells found in marrow that make bone and cartilage. The discovery opens the door to devising implants seeded with cells that can replace bone tissue lost to disease or injury. "These are pretty interesting molecules," explains Dr. Wan-Ju Li, a UW-Madison Professor of Orthopedics and Biomedical Engineering, of the bone marrow proteins lipocalin-2 and prolactin. "We found that they are critical in regulating the fate of mesenchymal stem cells." The open-access article is titled “Identification of Bone Marrow-Derived Soluble Factors Regulating Human Mesenchymal Stem Cells for Bone Regeneration.” Dr. Li and Dr. Tsung-Lin Tsai, a UW-Madison postdoctoral researcher, scoured donated human bone marrow using high-throughput protein arrays to identify proteins of interest and then determined the activity of mesenchymal stem cells exposed to the proteins in culture. A goal of the study, says Dr. Li, is to better understand the bone marrow niche where mesenchymal stem cells reside in the body so that researchers can improve culture conditions for growing the cells in the lab and for therapy. The Wisconsin researchers found that exposing mesenchymal stem cells to a combination of lipocalin-2 and prolactin in culture reduces and slows senescence, the natural process that robs cells of their power to divide and grow. Dr.

Landmark Genetic Study of Height in Humans

Variation in human height is partly due to diet and environment, but an estimated 80% of the variation is believed to be genetic. Combining genome-wide association methods and an unmatched dataset of more than 700,000 participants, a recent study narrowed down the set of candidate changes to 83 variants, some of which altering height by more than 2 cm (~0.8 inches). Over 300 scientists from across the globe, including researchers from the SIB Swiss Institute of Bioinformatics - among whom are group leaders Dr. Zoltán Kutalik, co-Principal Investigator of the paper, and Dr. Sven Bergmann - have combined their effort to study what makes us shorter or taller. In the context of precision medicine, the results also bring hope to understand the genetic basis of complex diseases such as diabetes or schizophrenia. The study was published online on February 1, 2017 in Nature. The article is titled “Rare and Low-Frequency Coding Variants Alter Human Adult Height.” Who will suffer from a heart attack before 55 years old despite a healthy lifestyle? Or which children will develop leukemia, and how will they respond to treatments? These and similar questions motivate precision medicine, that is an approach aiming to combine multiple types of data, including genetic information, to predict disease development and severity, and response to therapies. Adult height is mostly determined by the information encoded in our DNA: children from tall parents tend to be taller. “The idea is that if we can understand the genetics of a simple human trait like height, we could then apply this knowledge to develop tools to predict complex human diseases such as diabetes or schizophrenia,” explains Dr.

February 1st

Scientists Discover Peptide That Could Reduce Incidence of RSV-Related Asthma

A research report published in the February 2017 issue of the Journal of Leukocyte Biology shows that it may one-day be possible to reduce the incidence of asthma related to infection with respiratory syncytial virus (RSV). Specifically, the researchers found that a peptide, called STAT6-IP, when delivered to the lungs of neonatal mice at the time of first RSV exposure reduces the development of allergic-type lung inflammation and airway hyper-responsiveness ("twitchy" airways) in mice when they are "re-challenged" with RSV as young adults. "The incidence and severity of asthma and allergies have been increasing over the last 2-3 decades, affecting the general population in terms of both morbidity and cost. Our data suggest that exposure to STAT6-IP has the potential to modulate long-term responses to allergens and microbial antigens implicated in the development of asthma," said Brian J. Ward, M.D., a researcher involved in the work and Associate Professor from McGill University Health Centre, Research Institute in Montreal, Quebec, Canada. "A full understanding of how STAT6-IP works could open new approaches for therapy and long-term prevention of a variety of immunopathologic conditions beyond asthma. Indeed, our concept of peptide-based targeting of key transcriptional regulators could have broad implications for individuals at risk for many immune-mediated conditions." The new article is titled “STAT6 Inhibitory Peptide Given During RSV Infection of Neonatal Mice Reduces Exacerbated Airway Responses Upon Adult Reinfection.” To make their discovery, scientists infected mice with RSV, first as infants and then again as young adults. Mice were treated with STAT6-IP (or a control peptide) sprayed into the nose only at the time of the neonatal RSV infection.

“Mirror Game” Virtual Reality Test Could Enable Low-Cost Early Detection and Monitoring of Schizophrenia

Virtual reality could hold the key to unlocking an affordable, reliable, and effective device to provide early diagnosis and management of schizophrenia. A pioneering new study, led by experts from the University of Exeter (UK) in collaboration with partners from the Alterego FP7 EU project, has developed a new, “mirror game” test using computer avatars to accurately detect specific variations in how patients move and interact socially - well-documented characteristics of the mental disorder. For the study, the research team asked volunteers to perform a series of specific movements on their own, and then mirror some movements carried out by a computer avatar on a large screen placed opposite them. The results of these first trials revealed that the test gave a more accurate diagnosis when compared to clinical interviews, and comparable results when compared to more expensive, traditional neuroimaging methods, the team has concluded. The scientists believe it could open up new, unobtrusive pathways for health professionals to diagnose and treat schizophrenia in the future. They are now looking at conducting clinical trials to confirm the effectiveness of the early detection technique, before it can be employed in clinical practices worldwide. The study was published online in the leading scientific journal npj Schizophrenia on Wednesday, February 1 2017. The open-access article is titled “Unravelling Socio-Motor bBomarkers in Schizophrenia.” Dr. Piotr Slowinski, lead author of the study and a Mathematics Research Fellow at the University of Exeter, explained: "Human movement can give a fascinating and sophisticated insight into our personality traits and behavioral characteristics.