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Archive - 2015

December 7th

10th World Conference on Personalized Medicine to Be Held January 24-27, 2016 in Silicon Valley; Unprecedented Gathering of Luminaries in Rapidly Advancing Field That Promises to Change Medicine Forever

The Personalized Medicine World Conference (PMWC) 2016 will be held in Silicon Valley California, January 24-27, 2016. This will be the tenth annual PMWC and it promises to be an incredible gathering of major players in a field that is moving forward with astonishing speed and promises to revolutionize the practice of medicine. There will over 150 distinguished speakers and thousands of attendees from many areas of science and medicine. There are presently more than 70 corporate sponsors, and 25+ media partners. Detailed information on PMWC 2016 can be obtained at Conference session major themes include Genetics-Informed Personalized Immunotherapy, Non-Invasive Liquid Biopsies for Cancer Patients, The Microbiome—A Modifiable Biomarker, Data Solutions in Clinical Genomics, The Role of Practicing Pathologists in Personalized Medicine,, and Expansion of Non-Invasive Prenatal Testing. Four highly distinguished scientists will be recognized with awards. “Luminary Awards” will go to Laura Esserman, M.D., MBA, Director, Carol Franc Buck Breast Care Center, Professor of Surgery and Radiology, UCSF, Associate Director, UCSF Helen Diller Family Comprehensive Cancer Care Center, and to Roger Perlmutter, M.D., Ph.D., President, Merck Research Laboratories. “Pioneer Awards” will be presented to Ralph Snyderman, M.D, Chancellor Emeritus, Duke University, James B. Duke Professor of Medicine, Duke University School of Medicine, and to Irving Weissman, M.D., Director, Institute of Stem Cell Biology& Regenerative Medicine, Stanford University School of Medicine.

Discovery of Unique Muscle Fibers in Upper Airway; Fibers Present at Greater Numbers in Snorers & Sleep Apnea Patients; New Findings May Guide Future Treatments of Snoring, Sleep Apnea, and Swallowing Disorders

Researchers at Umeå University in Sweden have discovered unique muscle fibers in the soft palate of the mouth in both infants and adults. The fibers seem to be present in greater number in snorers and sleep apnea patients. The findings were published online on November 24, 2015 in the Journal of Anatomy. The article is titled “Unique Expression of Cytoskeletal Proteins in Human Soft Palate Muscles.” “This discovery of special group of fibers gives us deeper insight into the complex anatomy and physiology of the upper airway and evolutionary specialization. These unique fibers have a special molecular build-up with an absence or modified design of some key proteins. Surprisingly, absence of these proteins has only been reported in genetic muscular diseases,” says Farhan Shah, Ph.D., a researcher in the Department of Integrative Medical Biology at Umeå University and lead author of the article. The team at the Umeå University Laboratory of Muscle Biology, under the leadership of Associate Professor Per Stål, Ph.D., has taken a novel approach to see if snoring vibrations and tissue stretch can cause neuromuscular damage in upper airways and result in obstructive sleep apnea and swallowing dysfunction. These unique fibers were discovered while investigating muscles from both healthy subjects and obstructive sleep apnea patients. The ongoing project seeks to better understand upper airway muscle function in health and in disorders as obstructive sleep apnea, dysphagia, and speech disorders. Sleep apnea is associated with serious potential implications such as cardiovascular disorders, dementia and early death. “Our published findings are significant and will hopefully help guide more successful treatment strategies in the future.

Early Gene Therapy Results in Wiskott-Aldrich Syndrome Are Promising; Self-Inactivating Lentivirus Used for Gene Delivery; Four Treated Boys Show Improvement

On December 6, 2015, promising preliminary outcomes were reported for the first four children enrolled in a U.S. gene therapy trial for Wiskott-Aldrich syndrome (WAS), a rare, X-linked recessive, life-threatening blood and immune disorder. These new results were presented at the 57th Annual Meeting of the American Society of Hematology ( (abstract #260:, which is taking place in Orlando, Florida (December 5-8). All four boys are alive and have improved between 9 and 24 months following treatment, according to study principal investigator Sung-Yun Pai (photo), M.D., a pediatric hematologist/oncologist at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Since undergoing treatment, none of the four boys has experienced bleeding events or severe WAS-related infections. In addition, all four boys have experienced improvements in immunologic symptoms and variable improvements in platelet count. The two patients who had required medication to stimulate platelet production prior to undergoing gene therapy are no longer on those medicines. It is too early, however, to draw conclusions about long-term outcomes. The study protocol calls for the children to be monitored for 15 years in order to assess the treatment's safety and efficacy. WAS is caused by mutations that lead to the loss or dysfunction of the WAS gene, which is found on the X chromosome. The condition, which occurs only in boys, affects the development and function of T-cells and platelets, leaving patients vulnerable to bleeding, eczema, and infections. The only curative treatment is a hematopoietic (blood-forming) stem cell transplant from a compatible donor. However, it is often difficult to identify an appropriate match.

Thermal Ablation by MRI-Guided Ultrasound, Combined with Nanoparticle-Delivered Chemotherapy, Cures Tumors in Pre-Clinical Mouse Model of Breast Cancer

Thermal ablation with magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a noninvasive technique for treating fibroids and cancer. New research from the University of California, Davis (UC-Davias) shows that combining the technique with nanoparticle-delivered chemotherapy can allow complete destruction of tumors in mice. MRgFUS combines an ultrasound beam that heats and destroys tissue, with magnetic resonance imaging to guide the beam and monitor the effects of treatment. The effectiveness of the treatment can be limited by the need to spare normal tissue or critical structures on the tumor margins, as well as the need to eliminate micrometastases. In a open-access report published online on November 23, 2015 in The Journal of Clinical Investigation, Katherine W. Ferrara (photo), Ph.D., Distinguished Professor of Biomedical Engineering at UC-Davis, and colleagues report on a strategy that can destroy an entire tumor without thermal destruction of the tumor margin. Her group demonstrated a dramatic increase in the concentration of anti-cancer chemotherapy within several types of MRgFUS thermal ablation-treated tumors. The article is titled “Ultrasound Ablation Enhances Drug Accumulation and Survival in Mammary Carcinoma Models.” "MRgFUS is already FDA-approved for the treatment of uterine fibroids and palliation of bone metastases. We hope to expand the indication for MRgFUS by supplementing it with chemotherapy," said first author Andrew Wong, a graduate student with the UC Davis Physician Scientist Training Program. Dr. Ferrara's previous research has shown that ultrasound-induced mild hyperthermia can enhance the accumulation of tiny nanoparticles carrying anti-cancer drugs, but the accumulation is dependent on the type of tumor.

December 6th

Father’s Obesity Status Can Affect Children’s Health Via Dynamic Epigenetic Changes in Spermatozoa; Modifiable Pre-Conception Lifestyle Factors Could Be Hugely Significant; Autism Connection Also Suggested

Scientists have now shown that the obesity status of human fathers can dynamically alter the epigenome of their spermatozoa and such changes can be passed on to their children to have profound and lasting effects on the metabolism of future generations. In particular, in a multi-part study, the researchers first showed that spermatozoa from lean and from obese men differed significantly in the expression of many small non-coding RNA (sncRNA) molecules, a subtype of RNAs that is strongly implicated in epigenetic inheritance. More specifically, a particular subtype of sncRNAs, namely piwi-interacting RNAs (piRNAs), was found to be differentially expressed between lean and obese men. piRNAs are mainly expressed in the germline and are known to play a fundamental roles in maintaining genomic stability by repressing repetitive elements, and also in the regulating the expression of coding genes. A role for piRNAs in epigenetic inheritance has previously been demonstrated in Drosophila. In the current study, the scientists reported that target prediction of the piRNAs differentially expressed between lean and obese men retrieved genes with best enrichment scores for the terms ‘‘Chromosome’’ and ‘‘Chromatin’’ and the genetic annotation term ‘‘Chemdependancy.’’ Specifically, the cocaine and amphetamine regulated transcript (CART), a regulator of food intake involved in obesity, was differentially expressed in obese men.

December 4th

Schizophrenia Epigenetics: Environmental Influences Cause DNA Methylation Changes During Prenatal Period That Are Responsible for Frontal Cortex Brain Changes Associated with Schizophrenia

Researchers from the Lieber Institute for Brain Development (LIBD) affiliated with the Johns Hopkins University School of Medicine have reported results from one of the largest studies of post-mortem human brain tissue that suggest that environmental influences during the prenatal period cause brain changes associated with schizophrenia, but that environmental influences in early adulthood, when symptoms of the illness typically emerge, may not be as important as originally thought. The study and its relevant findings were published online on November 30, 2015 in Nature Neuroscience. The article is titled “Mapping DNA Methylation Across Development, Genotype, and Schizophrenia In the Human Frontal Cortex.” Findings outlined in the paper shed new light on the potential role of environmental influences on an individual’s risk of developing schizophrenia. The role of the environment in causing schizophrenia is a hotly debated topic, with many theories focusing on the stressful environment in the early adult period that typically heralds the onset of clinical symptoms of schizophrenia. In this study, results suggest that the prenatal period, not early adulthood, is when environmental influences cause brain changes involving DNA methylation that are associated with a greater risk of schizophrenia. The environment can affect human biology, e.g., how your brain responds to experience, or how your body responds to exercise, by influencing the mechanisms that turn genes on and off. One of these mechanisms is called “epigenetics,” which involves changes in the chemical structure of DNA without changes in the inherited genetic code itself. DNA methylation is an epigenetic change that can signal an environmental effect.

December 4th

Schizophrenia Epigentics: International Study Shows Genetic Risk Factors Are Associated with DNA Methylation Differences As Early As First & Second Trimester of Life

An international research collaboration has shed new light on how DNA sequence variation can influence gene activity in the developing human brain. The multi-national team, which was led by researchers at the University of Exeter Medical School, at King's College London, and at Cardiff University in Wales, conducted what was described as the first study of how genetic variation influences DNA methylation, an epigenetic modification that can have direct effects on gene expression and function, in the developing brain. In research published online on November 30, 2015 in Nature Neuroscience and funded by the UK’s Medical Research Council (MRC), the researchers demonstrated the potential utility of such data for refining the genetic signals associated with diseases hypothesized to have a neurodevelopmental component, such as schizophrenia. The article is titled “Methylation QTLs in the Developing Brain and Their Enrichment in Schizophrenia Risk Loci.” [Please also note BioQuick’s coverage of a different schizophrenia epigenetics study also published online on November 30. 2015 in Nature Neuroscience (]. DNA methylation is a chemical modification to one of the four bases that make up our genetic code, controlling when and where genes are expressed. As with other epigenetic marks, it is known to be dynamic across the course of life and modifiable by a number of factors, including the underlying genetic sequence. DNA methylation represents one possible pathway between genetic variation and disease, with genetic differences altering the regulation of gene expression at specific points in development.

Feral Cats in Australia Descended from Cats Brought by European Settlers in 1800's; Australia’s Feral Cats Currently Threaten Over 100 Native Species; New Study Has Implications for Management of Invasive Species

Researchers have found that feral cats in Australia are most likely descended from cats brought to the continent by European settlers. Feral cats found on the islands surrounding Australia may represent founding populations from Europe, introduced in the 19th century, according to research published online today (December 4, 2015) in open access journal BMC Evolutionary Biology. The article is titled "A Voyage to Terra Australis: Human-Mediated Dispersal of Cats." Identifying the timing of the founding of these cat populations increases our knowledge of the effects ths invasive species had when introduced to Australia. Feral cats (i.e., cats that are free-living and independent of humans, but that are descended from cats that did rely on humans) have established invasive populations over large geographic areas of Australia. There has been much debate about how these cats arrived in Australia. Cats were often transported on sailing vessels as a means of controlling rodents or as pets, initially on board and then in new settlements. One theory suggests that cats arrived in Australia with European explorers in the late 18th century. Another hypothesis is that cats accompanied Malaysian trepangers (Malaysian fishers of sea cucumbers) northern Australia in approximately 1650. Researchers from the Senckenberg Biodiversity and Climate Research Centre (BiK-F) and the University of Koblenz-Landau, Germany analyzed mitochondrial DNA and microsatellites (short repeating sequences of DNA) from 266 Australian feral cats to explore their evolutionary history and dispersal patterns. Samples were analyzed from six mainland and seven island locations. The analysis found that the most probable primary source of feral cats in Australia is from cats arriving from Europe in the 19th century.

Activated Notch Signaling Pathway Suppresses Formation of Certain Gliomas; Inactivation of Pathway Leads to Accelerated Growth; Major Differences Seen in Molecular Requirements of Seemingly Similar Brain Tumors

Researchers at the University of Basel in Switzerland have taken a close look at a signaling pathway (Notch) present in most organisms and found that it suppresses the formation of specific types of brain tumor. Their results have been published online today (December 4, 2015) in an open-access article in Cancer Cell. The article is titled “A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes.” Gliomas are the most common brain tumors in adults and the prognosis for patients is, in many cases, very bad. Therefore, novel and effective therapies for glioma treatment are needed. In order to develop these, it is crucial to understand the biology of this type of tumor. So far, it has been highly debated as to which brain cells can form gliomas when they acquire gene mutations. However, researchers believe that brain stem cells might be a potential source of this type of cancer. Stem cells in the human brain can generate new nerve cells and, if something goes wrong in this process and uncontrolled proliferation or impaired differentiation occurs, this may lead to the formation of a brain tumor. A research team led by Professor Verdon Taylor from the Department of Biomedicine at the University of Basel has now studied whether one molecular mechanism that controls normal stem cell maintenance in the brain is hijacked and used by cancer cells during tumor formation. The researchers studied the so-called Notch pathway. This signaling pathway is central to brain stem cell activity and it has been proposed that it can, once aberrantly activated, contribute to the growth of gliomas. “In contrast to our expectations, we found that the opposite is the case: when activated, this pathway actually suppresses the formation of some types of glioma”, says Claudio Giachino, Ph.D., first author of the study.

December 3rd

Broad & MIT Scientists Engineer Slightly Altered Cas9 Enzyme to Dramatically Reduce Off-Target Effects of CRISPR/Cas9 Genome Editing; Modified Enzyme Made Available to Labs Worldwide

Researchers at the Broad Institute of MIT and Harvard and at the McGovern Institute for Brain Research at MIT have engineered changes to the revolutionary CRISPR/Cas9 genome editing system that significantly cut down on "off-target" editing errors. The refined technique addresses one of the major technical issues in the use of genome editing. The CRISPR/Cas9 system works by making a precisely targeted modification in a cell's DNA. The protein Cas9 alters the DNA at a location that is specified by a short RNA strand whose sequence matches that of the target site. While Cas9 is known to be highly efficient at cutting its target site, a major drawback of the system has been that, once inside a cell, Cas9 can bind to and cut at additional sites that are not targeted. This has the potential to produce undesired edits that can alter gene expression or knock a gene out entirely, which might lead to the development of cancer or other problems. In a paper published online on December 1, 2015 in Science, Feng Zhang, Ph.D., and his colleagues report that changing just 3 of the approximately 1,400 amino acids that make up the Cas9 enzyme from S. pyogenes dramatically reduced "off-target editing" to undetectable levels in the specific cases examined. The Science article is titled “Rationally Engineered Cas9 Nucleases with Improved Specificity.” Dr. Zhang and his colleagues used knowledge about the structure of the Cas9 protein to decrease off-target cutting. DNA, which is negatively charged, binds to a groove in the Cas9 protein that is positively charged. Knowing the structure, the scientists were able to predict that replacing some of the positively charged amino acids with neutral ones would decrease the binding of "off target" sequences much more than the binding of "on target" sequences.