Syndicate content

Precision Medicine World Conference (PMWC) 2019 Conference in January in Silicon Valley; Q&A Session with Luminary Award Winner Genetic Alliance CEO Sharon Terry Available Now

The Precision Medicine World Conference (PMWC), celebrating ten years of operation, will take place at the Santa Clara Convention Center (Silicon Valley, California) January 20-23, 2019. This is expected to be the largest Precision Medicine World Conference ever, with 2,500 attendees. This amazing gathering of prestigious experts in multiple inter-related fields and those interested in learning more is co-hosted by UCSF, Stanford Health Care/Stanford Medicine, Duke University, Duke Health, and Johns Hopkins University. The program will cover innovative technologies, thriving initiatives, and clinical case studies that enable the translation of precision medicine into direct improvements in health care. Conference attendees (https://www.pmwcintl.com/about/#audience) will have an opportunity to learn first-hand about the latest developments and advancements in precision medicine and cutting-edge new strategies and solutions that are changing how patients are treated. The conference’s five-track program will include sessions on the following major topics, among many others: AI & Data Science; Clinical & Research Tools; Clinical Diagnostics; Creating Clinical Value with Liquid Biopsy ctDNA, etc.; Digital Health/Health and Wellness; Pharmacogenomics; Emerging Technologies in Precision Medicine; Immunotherapy; Large-Scale Bio-Data Resources to Support Drug Development; Rare Disease Diagnosis; and Wellness & Aging. Conference organizers have assembled a hugely impressive lineup of 450+ highly regarded speakers, featuring pioneering researchers and authorities across the healthcare and biotechnology sectors (https://www.pmwcintl.com/2019sv/speakers/).

Thousands of Recombination Events Identified in APP Gene in Alzheimer’s Brains; Changes Depend on Reverse Transcriptase; “Findings Provide Scientific Rationale for Immediate Clinical Evaluation of HIV Antiretroviral Therapies in People with Alzheimer's"

Scientists from Sanford Burnham Prebys Medical Discovery Institute (SBP) in San Diego, California, have identified gene recombination in neurons that produces thousands of new gene variants within Alzheimer's disease brains. The study, published online on November 21, 2018 in Nature, reveals for the first time how the Alzheimer's-linked gene, APP (the gene coding for amyloid precursor protein--see image), is recombined by using the same type of enzyme found in HIV. The article is titled “Somatic APP Gene Recombination in Alzheimer’s Disease and Normal Neurons.” Using new analytical methods focused on single and multiple-cell samples, the researchers found that the APP gene, which produces the toxic beta amyloid proteins defining Alzheimer's disease, gives rise to novel gene variants in neurons--creating a genomic mosaic. The process required reverse transcription and reinsertion of the variants back into the original genome, producing permanent DNA sequence changes within the cell's DNA blueprint. "We used new approaches to study the APP gene, which gives rise to amyloid plaques, a pathological hallmark of the disease," says Jerold Chun, MD, PhD, , senior author of the paper and Professor and Senior Vice President of Neuroscience Drug Discovery at SBP. "Gene recombination was discovered as both a normal process for the brain and one that goes wrong in Alzheimer's disease." One hundred percent of the Alzheimer's disease brain samples contained an over-abundance of distinct APP gene variants, compared to samples from normal brains. Among these Alzheimer's-enriched variations, the scientists identified 11 single-nucleotide changes identical to known mutations in familial Alzheimer's disease--a very rare inherited form of the disorder.

Enzyme on Surface of Some Lung Cancers Enhances Cancer Growth & May Be Target for Treatment

University of Texas (UT) Southwestern researchers have found that an enzyme on the surface of some lung cancer cells helps feed the cancer, making it a tempting treatment target. The enzyme, transmembrane serine protease 11B (TMPRSS11B), is described in a report published in the November 20, 2018 issue of Cell Reports. The open-access article is titled “Transmembrane Protease TMPRSS11B Promotes Lung Cancer Growth by Enhancing Lactate Export and Glycolytic Metabolism.” In addition to being found in squamous cell lung cancer and prostate cancer, the enzyme also has been identified in squamous cell head, neck, and cervical cancers, said Dr. Kathryn O’Donnell (photo), Assistant Professor of Molecular Biology. Her team identified TMPRSS11B while searching for genes that can convert precancerous lung cells into malignant cells that can form tumors. “In this study, we found that the enzyme strongly promoted the growth of certain types of lung cancer cells. We uncovered a new mechanism that expands our understanding of how cancer cells reprogram their metabolism to provide energy for rapid growth as they form tumors,” Dr. O’Donnell said. The researchers noticed that the enzyme was expressed at increased levels in human squamous cell lung cancers – a common type of non-small cell lung cancer – and that suppressing the levels of TMPRSS11B through gene editing or RNA interference reduced tumor growth in mouse models, she said. The research focused on TMPRSS11B’s ability to encourage the movement of lactate, a byproduct of cell metabolism long thought to be a waste product. Ground-breaking research last year from UT Southwestern Professor Dr. Ralph DeBerardinis’ laboratory found that, in fact, lactate provides fuel for growing tumors. Dr.

DNA Vaccine Reduces Both Toxic Proteins (Beta-Amyloid & Tau) Linked to Alzheimer’s in Mouse Model

A DNA vaccine tested in mice reduces accumulation of both types of toxic proteins associated with Alzheimer’s disease, according to research that scientists say may pave the way to a clinical trial. A new study by the University of Texas (UT) Southwestern’s Peter O’Donnell Jr. Brain Institute shows that a vaccine delivered to the skin prompts an immune response that reduces buildup of harmful tau and beta-amyloid – without triggering severe brain swelling that earlier antibody treatments caused in some patients. “This study is the culmination of a decade of research that has repeatedly demonstrated that this vaccine can effectively and safely target in animal models what we think may cause Alzheimer’s disease,” said Dr. Roger Rosenberg, founding Director of the Alzheimer’s Disease Center at UT Southwestern. “I believe we’re getting close to testing this therapy in people.” The research, published online on October 20, 2018 in Alzheimer’s Research and Therapy, demonstrates how a vaccine containing DNA coding for a segment of beta-amyloid also reduces tau in mice modeled to have Alzheimer’s disease. In addition, the vaccine elicits a different immune response that may be safe for humans. The open-accessa article is titled “Active Full-Length DNA Aβ42 Immunization in 3xTg-AD Mice Reduces Not Only Amyloid Deposition But Also Tau Pathology.” Two previous studies from Dr. Rosenberg’s lab showed similar immune responses in rabbits and monkeys. The vaccine is on a shortlist of promising antibody treatments aimed at protecting against both types of proteins that kill brain cells as they spread in deadly plaques and tangles on the brains of Alzheimer’s disease patients. Although earlier research established that antibodies significantly reduce amyloid buildup in the brain, Dr. Rosenberg’s team needed to find a safe way to introduce them into the body.

Activation of Inhibitory Neurons Prior to Epileptic Seizures Observed for First Time in Humans

(BY RACHEL DERITA, PhD Candidate,Thomas Jefferson University, Department of Cancer Biology) Epileptic seizures are established to neuroscience as global excitation of neurons in the brain. However, new research from Jefferson (Philadelphia University & Jefferson University) in Philadelphia and collaborating institutions has uncovered a previously unknown period of time before an epileptic seizure in which there is an activation of inhibitory neurons. “This is the first time, to our knowledge, that this phenomenon of inhibition at the start of a seizure has been observed in humans,” states senior author of the study Shennan Weiss, MD, PhD, Assistant Professor of Neurology and Head of the Thomas Jefferson Computational Epilepsy Laboratory at the Vickie & Jack Farber Institute for Neuroscience at Jefferson. Before now, this was a phenomenon only observed in chemically-induced seizures in research animals, and was therefore considered an artifact of the experimental models. In the current study, published online on September 4, 2018, in the Annals of Neurology, surgeons collaborating between Jefferson and the University of California at Los Angeles (UCLA), used electrodes to determine the exact location of the seizures occurring in an epilepsy patient. They then were able to track action potentials from single neurons, classified as either excitatory or inhibitory. It was observed that there was a burst of activity from the inhibitory neurons prior to activity of the excitatory neurons. Epileptic patients often experience a period of time prior to a seizure characterized by auras, confusion, and an inability to speak clearly or form coherent sentences.

New Work Suggests That Non-Homologous End-Joining (NHEJ) & Retrotransposons Led to Evolution of Spliceosome and Advance of Eukaryotic Life

A previously unappreciated interaction in the genome turns out to have possibly been one of the driving forces in the emergence of advanced life, billions of years ago. This discovery began with a curiosity for retrotransposons, known as "jumping genes," which are DNA sequences that copy and paste themselves within the genome, multiplying rapidly. Nearly half of the human genome is made up of retrotransposons, but bacteria hardly have them at all. Nigel Goldenfeld, PhD, Swanlund Endowed Chair of Physics at the University of Illinois at Urbana-Champaigne (UIUC), and Director of NASA Astrobiology Institute for Universal Biology at UIUC; and Thomas Kuhlman, PhD, a former Physics Professor at UIUC who is now at the University of California, Riverside, wondered why this is. "We thought a really simple thing to try was to just take one (retrotransposon) out of my genome and put it into the bacteria just to see what would happen," Dr. Kuhlman said. "And it turned out to be really quite interesting." Their results, published online on November 19, 2018 in PNAS, give more depth to the history of how advanced life may have emerged billions of years ago -- and could also help determine the possibility and nature of life on other planets. The title of the open-access PNAS article is “Testing the Retroelement Invasion Hypothesis for the Emergence of the Ancestral Eukaryotic Cell.”Along the way to explaining life, the researchers first encountered death -- bacterial death, that is. When they put retrotransposons in bacteria, the outcome was fatal. "As they jump around and make copies of themselves, they jump into genes that the bacteria need to survive," Dr. Kuhlman said. "It's incredibly lethal to them."

Good Nutrition Could Protect Children from Cognitive Difficulties Caused by Early-Life Stress

Good nutrition in early life may protect against stress-induced changes in brain development in young mice, according to data presented at the Society for Endocrinology 2018 Annual Conference in Glasgow (November 19-21). The study findings suggests that a nutrient-rich diet may have protective effects on brain development in young mice exposed to early-life stress, which reduces their risk of learning and memory issues in later life. It has been reported, in humans and animals, that exposure to adversities, such as stress, in early life can have long-lasting effects on brain function, and may lead to cognitive problems in later life. The period just after birth is critical for brain development and demand for nutrients is high, both for energy and as essential building blocks for the developing brain. Therefore any deficit in essential nutrients during this time could result in long-lasting abnormalities in brain function, including learning processes. The stress and metabolic processes of the body are closely interlinked, and whether stress-related cognitive problems in early life can be prevented or even reversed by ensuring good nutrition has not been fully investigated. In this study, Dr. Aniko Korosi and colleagues from the University of Amsterdam, investigated the effects of essential nutrients on brain function using a mouse model of early-life stress. Early-life stress was mimicked by reducing the amount of maternal care and attention given to pups within the first 2 weeks of birth. By the age of 4 months, these neglected mice show several impairments, including increased body fat levels, high stress hormone levels, and poor performance in learning and memory tasks.

Michael Bloomberg Gives Record $1.8 Billion to Johns Hopkins for Financial Aid--Historic Gift Is Largest Ever to a US College or University

Philanthropist, business leader, and three-term New York City Mayor Michael R. Bloomberg will commit a record-breaking $1.8 billion to support undergraduate financial aid at Johns Hopkins, the university announced on October 18, 2018, the largest-ever single contribution to a US college or university. "This historic gift reflects Mike Bloomberg's deep belief in the transformative power of higher education and his insistence that it be accessible to all qualified students, regardless of financial means," Johns Hopkins University President Ronald J. Daniels wrote in a message to the university community today (see text below). "It also affirms Mike's profound devotion to this university for the role that it played in enriching his life." Bloomberg, a 1964 Johns Hopkins graduate, announced his historic gift in a New York Times op-ed (https://www.nytimes.com/2018/11/18/opinion/bloomberg-college-donation-fi...) in which he identified college affordability as a national challenge. "America is at its best when we reward people based on the quality of their work, not the size of their pocketbook," Bloomberg said. "Denying students entry to a college based on their ability to pay undermines equal opportunity. It perpetuates inter-generational poverty. And it strikes at the heart of the American dream: the idea that every person, from every community, has the chance to rise based on merit." For more on Bloomberg's gift, read the full text of President Daniels' message to the community below. "Dear Members of the Johns Hopkins Community:

Exosomes “Swarm” to Protect Against Bacteria Inhaled Through Nose; “Armed” Exosomes Contain Increased Nitric Oxide Synthase to Make Potent Anti-Bacterial Compound (Nitric Oxide); Finding May Also Lead to Improved Airway Drug Delivery

Bacteria are present in just about every breath of air we take in. How the airway protects itself from infection from these bacteria has largely remained a mystery — until now. When bacteria are inhaled, exosomes, or tiny fluid-filled vesicles, are immediately secreted from cells that directly attack the bacteria and also shuttle protective antimicrobial proteins from the front of the nose to the back along the airway, protecting other cells against the bacteria before they get too far into the body. A research team from Massachusetts Eye and Ear describes this newly discovered mechanism in a report publishd online on November 12, 2018 in the Journal of Allergy and Clinical Immunology (JACI). The findings shed new light on our immune systems — and also pave the way for drug delivery techniques to be developed that harness this natural transportation process from one group of cells to another. The article is titled “Exosome Swarms Eliminate Airway Pathogens and Provide Passive Epithelial Immunoprotection Through Nitric Oxide.” “Similar to kicking a hornets’ nest, the nose releases billions of exosomes into the mucus at the first sign bacteria, killing the bacteria and arming cells throughout the airway with a natural, potent defense,” said senior author Benjamin S. Bleier, MD, a sinus surgeon at Massachusetts Eye and Ear and Associate Professor of Otolaryngology at Harvard Medical School. “It’s almost like this swarm of exosomes vaccinates cells farther down the airway against a microbe before they even have a chance to see it.” The JACI study was motivated by a perplexing previous finding from Dr. Bleier’s lab a few years ago. In studies of sinus inflammation, researchers found that proteins in the cells of the nasal cavity were also present in patients’ nasal mucus.

Non-Coding Rare Genetic Variant (rs17114036) Could Improve Key Vascular Functions and May Reduce Risk of Risk of Coronary Artery Disease (CAD)

Atherosclerotic disease, the slow and silent hardening and narrowing of the arteries, is a leading cause of mortality worldwide. It is responsible for more than 15 million deaths each year, including an estimated 610,000 people in the United States. In an pen-access article published online on November 14, 2018 in PNAS, a team of physicians, geneticists, and biologists describes a previously unknown genetic factor that can either raise or reduce the risk of coronary artery disease or ischemic stroke. The article is titled “Genetic Variant at Coronary Artery Disease & Ischemic Stroke Locus 1p32.2 Regulates Endothelial Responses to Hemodynamics.” The researchers found that a common non-coding sequence of DNA -- known as rs17114036 and located on chromosome 1p32.2 -- helps regulate gene expression in the cells that line the interior surface of blood vessels, the vascular endothelium. This sequence of DNA contains a single nucleotide polymorphism (SNP). SNPs are common. There is, on average, 1 SNP for every 300 nucleotides scattered throughout a person's DNA. SNPs tend to reside between genes. Most have no known effect, but some play a distinct role. The research team found that rs17114036 plays a significant role in endothelial function and is relevant to human disease incidence. "This particular polymorphism is a previously unappreciated layer of regulatory control," said Yun Fang, PhD, an Assistant Professor of Medicine at the University of Chicago and senior author of the study. The endothelium helps smooth and speed the flow of blood through complex vascular intersections, places where branches or bifurcations disrupt the flow from an artery to two smaller vessels. When the flow is smooth and in one direction, the endothelium is quiescent.

Syndicate content