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News Article | May 8, 2017
Site: www.eurekalert.org

PHOENIX, Ariz. -- May 8, 2017 -- Dr. Daniel Von Hoff -- Distinguished Professor, Physician-In-Chief, and Director of Molecular Medicine at the Translational Genomics Research Institute (TGen) -- will receive a gold medal for excellence in clinical medicine from his alma mater, Columbia University. Columbia University College of Physicians and Surgeons Alumni Association will present the award May 13 in New York City to Dr. Von Hoff, a world-renowned expert in new therapies for patients with cancer. "This medal represents the highest honor which the Alumni Association can bestow in recognition of your outstanding accomplishments," said Dr. Kenneth A. Forde, chair of the P&S Alumni Association Honors and Awards Committee, which represents some of the nation's most accomplished medical professionals. This year marks the 250th anniversary of P&S, and its founding as the first medical school in Colonial America to award an Medical Doctorate degree. "This recognition is especially gratifying as it is being presented by notable fellow graduates of my medical school, and I am deeply humbled and appreciative to be counted among those devoted to the welfare of patients," said Dr. Von Hoff, who has been instrumental in developing numerous new cancer treatments. He also is a Senior Consultant-Clinical Investigations for City of Hope, Chief Scientific Officer at HonorHealth Research Institute, and Professor of Medicine at Mayo Clinic. Dr. Von Hoff currently co-leads an international Stand Up To Cancer (SU2C) Pancreatic Cancer Dream Team, developing new treatments for this disease. It is one of three SU2C Dream Team grants awarded to TGen. He graduated cum laude from Carroll University (1969), and received his M.D. from Columbia University College of Physicians and Surgeons (1973). He completed his internship and residency in internal medicine at the University of California, San Francisco, then completed a medical oncology fellowship at the National Cancer Institute. Dr. Von Hoff is a past director of the University of Arizona's Arizona Cancer Center. He also is a past board member and president of the American Association for Cancer Research (AACR), a Fellow of the AACR, and recipient of the distinguished AACR Richard and Hinda Rosenthal Memorial Award. In addition, he is a past board member of the American Association of Clinical Oncology (ASCO) and winner of its prestigious David A. Karnofsky Memorial Award for outstanding contributions to patient care and treatment. He served a six-year term on President Bush's National Cancer Advisory Board (2004-10); is a recipient of the Wallace A. Reed M.D. Award, recognizing his accomplishments in advancing innovative cancer treatments, from the Arizona Medical Association; and received the Award of Excellence from the Hope Funds for Cancer Research, for his work in the clinical development of many new cancer treatments. Dr. Von Hoff and his colleagues have conducted early clinical investigations of many new cancer agents, including: gemcitabine, docetaxel, paclitaxel, topotecan, irinotecan, nanoliposomal irinotecan, fludarabine, mitoxantrone, dexrazoxane, nab-paclitaxel, vismodegib, and others. These treatments are helping many patients with breast, ovarian, prostate, colon, leukemia, advanced basal cell and pancreatic cancers. Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. TGen is focused on helping patients with neurological disorders, cancer, and diabetes, through cutting edge translational research (the process of rapidly moving research towards patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children. Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. TGen is allied with City of Hope, a world-renowned independent research and cancer and diabetes treatment center. This precision medicine alliance enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. For more information, visit: http://www. . Follow TGen on Facebook, LinkedIn and Twitter @TGen.


ATLANTA--Dr. Ming-Hui Zou, director of the Center for Molecular & Translational Medicine and a Georgia Research Alliance Eminent Scholar in Molecular Medicine, has received a five-year, $2.3 million federal grant to study how to reduce tumor growth in lung cancer. In the United States, more people die from lung cancer than any other type of cancer, according to the Centers for Disease Control and Prevention. In 2013, the most recent year for which statistics are available, 212,584 people were diagnosed with lung cancer and 156,176 people died from lung cancer. As cancer develops, tumor cells release substances that promote the formation of new blood vessels, known as pro-angiogenic factors, by stimulating a response from endothelial cells, which line the inner walls of blood vessels. This leads to increased angiogenesis (the formation of new blood vessels), tumor growth and the spread of cancer. Scientists have developed therapies that target vascular endothelial growth factor (VEGF), a potent angiogenic factor. However, the benefits of anti-VEGF therapies are often temporary because tumors become resistant to this therapy and start inducing new blood vessel formation with other pro-angiogenic factors. As a result, there's an urgent need to find novel targets for treatment. This grant from the National Cancer Institute of the National Institutes of Health will help Zou determine the molecular mechanism by which Liver Kinase B1 (LKB1), a tumor suppressor gene, suppresses transcriptional (gene) expression and activity of VEGF, NRP-1 and other pro-angiogenic factors, resulting in a reduction in tumor growth and a restriction in blood supply to tumors. "The completion of this project will allow us to identify that enhancing LKB1 activity or expression is not only beneficial in suppressing cancer progression/metastasis but also in treating ischemic heart diseases," Zou said. The project has three aims. The first is to establish if LKB1 leads to decreased VEGF expression through impeding the activation of transcription, the first step of gene expression, in endothelial cells. The second aim is to establish if LKB1 suppresses NRP-1 and other non-VEGF growth factor-mediated angiogenesis in tumor cells. The third aim is to determine the contribution of LKB1 down-regulation of VEGF and NRP-1 within the vascular niche in mice. An abstract of the grant, 1R01CA213022-01, is available at NIH's Project RePORTer website. For more information about the Center for Molecular & Translational Medicine, visit http://medicine. .


News Article | February 15, 2017
Site: www.scientificamerican.com

When a mother gives birth vaginally and if she breastfeeds, she passes on colonies of essential microbes to her baby. This continues a chain of maternal heritage that stretches through female ancestry for thousands of generations, if all have been vaginally born and breastfed. This means a child’s microbiome, that is the trillions of microorganisms that live on and in him or her, will resemble the microbiome of his/her mother, the grandmother, the great-grandmother and so on, if all have been vaginally born and breastfed. To use an analogy, pregnancy sets the conditions for a big party to take place in the baby’s gut. This once-in-a-lifetime event is open to everyone, but especially welcome are the VIP guests, the mother’s vaginal, gut and breast milk microorganisms. During pregnancy, the baby is mostly protected from harmful microorganisms by the amniotic sac, but recent research suggests the baby could be exposed to small quantities of microbes from the placenta, amniotic fluid, umbilical cord blood and fetal membranes. One theory is that any possible prenatal exposure could ‘pre-seed’ the infant microbiome. In other words, to set the right conditions for the ‘main seeding event’ for founding the infant microbiome. As soon as the mother’s waters break, this is the moment the party doors swing open, the stereo is switched on and the first VIP party guests flood in. Suddenly the baby is exposed to a wave of the mother’s vaginal microbes that wash over the baby in the birth canal. They coat the baby’s skin, and enter the baby’s eyes, ears, nose and some are swallowed to be sent down into the gut. More VIP guests in the form of the mother’s gut microbes join the colonisation party through contact with the mother’s faecal matter. Many more microbes come from every breath, from every touch including skin-to-skin contact with the mother and of course, from breastfeeding. Inside breast milk, you have special sugars called human milk oligosaccharides (HMO’s) that are indigestible by the baby. These sugars are designed to feed the mother’s VIP microbes newly arrived in the baby’s gut. The HMO’s feed the party guests, fuelling the party spirit, so that the microbes quickly multiply. By multiplying quickly, the ‘good’ VIP bacteria crowd out any potentially harmful gate-crashing pathogens. These ‘good’ bacteria help train the baby’s naive immune system, teaching it to identify what is friend to be tolerated, what is pathogen to be attacked. In other words, the mother’s bacteria teach security who to keep in the party, and who to eject. If the party gets off to a great start, and the chain of maternal heritage continues, this leads to the optimal training of the infant immune system resulting in a child’s best possible lifelong health. With C-section and formula feeding, the baby is not likely to acquire the full complement of the mother’s vaginal, gut and breast milk microbes. Therefore, the baby’s microbiome is not likely to closely resemble the mother’s microbiome. A baby born by C-section is likely to have a different microbiome from its mother, its grandmother, its great-grandmother and so on. C-section breaks the chain of maternal heritage and this break can never be restored. From that moment on, a different set of microbes will be passed on to that child’s child, to that child’s grandchild, and great-grandchild and so on. Returning to the party analogy, there’s a different crowd at the gut colonisation party with a baby born by C-section. You’ll still have the party guests coming from the air and from every touch, but at least with elective C-section, you won’t have the VIP party guests from the mother’s vagina and gut. (With emergency C-section, there might be some exposure to the mother’s vaginal microbes during labor if the waters have broken prior to surgery.) In nine recent cohort studies,* the microbial profiles of babies born by C-section have a lower abundance of the species Bacteroides than vaginally born babies. A very recent study published by Chu. D et al., in Nature Medicine 2017, also shows this lower abundance of Bacteroides in their cladograms and heatmaps, but the researchers chose not to report this data in numbers. What does an altered microbiome mean for a child’s lifelong health? Causation is still to be proven, but many studies link C-section with a significantly increased risk for developing asthma, Type 1 diabetes, celiac disease and obesity. With formula feeding, the baby won’t receive the 700 species of microbes found in breast milk. The baby also won’t receive the human milk oligosaccharides that provide the perfect food to feed the microbes newly arrived from the mother‘s vagina and gut (if vaginally born). Plus, formula milk is likely to contain other bacteria that are not supposed to be there, for these might interfere with the optimal training of the immune system, with consequences for a child’s lifelong health. Over the past five years, through co-directing the award-winning documentary MICROBIRTH and through co-authoring the book, YOUR BABY’S MICROBIOME, I’ve interviewed dozens of world-leading professors about their research. Scientists might not yet have all the pieces, but the picture that is forming is that C-section and formula feeding could be significantly impacting the health of the next generation. Through the transgenerational aspect to birth, it could even be impacting the health of future generations. In other words, we risk breaking the chain of maternal heritage at our peril. *Nine Cohort studies showing consistency of low abundance of Bacteroides for babies born by C-section: Jakobsson et al. 2014, Azad et al. 2016, Hesla et al. 2014, Backhed et al. 2015, Penders et al. 2013, Madan et al. 2016, Dogra et al. 2015, Martin et al. 2016, Yassour, et al. 2016 The Completed Self: An Immunological View of the Human-Microbiome Superorganism and Risk of Chronic Diseases. Dietert, Rodney R., and Janice M. Dietert. Entropy 14 (2012): 2036–65, doi:10.3390/e14112036. The Infant Microbiome Development: Mom Matters Noel T. Mueller, Elizabeth Bakacs, Joan Combellick, Zoya Grigoryan, and Maria G. Dominguez-Bello, Trends in Molecular Medicine 21, no. 2 (January 8, 2015): 109–17, doi:10.1016/j. molmed.2014.12.002. The Placenta Harbors a Unique Microbiome Kjersti Aagaard, Jun Ma, Kathleen M. Antony, Radhika Ganu, Joseph Petrosino, and James Versalovic, Science Translational Medicine 6, no. 237 (May 21, 2014): 237ra65, doi:10.1126/ scitranslmed.3008599. CHILD Study Investigators. Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study. Azad MB , Konya T , Persaud RR , Guttman DS , Chari RS , Field CJ , Sears MR , Mandhane PJ , Turvey SE, Subbarao P , Becker AB , Scott JA , Kozyrskyj AL , BJOG : an international journal of obstetrics and gynaecology. 2016; 123(6): 983-993. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery Derrick M Chu, Jun Ma, Amanda L Price, Kathleen M Anthony, Maxim D Seferovic & Kjersti M Aagard, Nature Medicine (2017) doi:10.1038/nm.4272


News Article | February 15, 2017
Site: www.eurekalert.org

Kent researchers have identified how few mutations it can take for Ebolaviruses to adapt to affect previously resistant species Kent researchers have identified how few mutations it can take for Ebolaviruses to adapt to affect previously resistant species. Ebola is one of the world's most virulent diseases, though rodent species such as guinea pigs, rats and mice are not normally susceptible to it. However, through repeated infection of a host animal, Ebola virus strains can be generated that replicate and cause disease within new host rodent species. Scientists in the University of Kent's School of Biosciences examined the changes associated with Ebolavirus adaptation to rodents including guinea pigs and mice across four different studies. They found that only very few mutations, probably fewer than five, are required for the virus to adapt. In particular, a change in the Ebolavirus protein VP24 seems to be critical for Ebola viruses to infect a new animal species. Ebolaviruses infecting domestic species, including pigs and dogs, may also result in virus changes that may increase the risk to humans. Reston viruses, Ebolaviruses that have not been shown to cause disease in humans, so far, are known to circulate in domestic pigs in Asia. The research was performed by Dr Mark Wass (Senior Lecturer in Computational Biology), Professor Martin Michaelis (Professor of Molecular Medicine), and Dr Jeremy Rossman (Senior Lecturer in Virology) and members of their research groups. The research, entitled Changes associated with Ebola virus adaptation to novel species, was published in the journal Bioinformatics. See here: https:/ For further information or interview requests contact Sandy Fleming at the University of Kent Press Office. News releases can also be found at http://www. The recent Ebola virus epidemic in West Africa, which resulted in more than 28,000 confirmed cases and more than 11,000 deaths, raised concerns that similar (or even larger epidemics) may occur in the future. Ebolaviruses are zoonotic viruses, transmitted between different animal species and humans are typically infected by animals. The species in which Ebolaviruses are continuously circulating remain to be identified, although some bats have been suspected to be carriers. Zoonotic viruses that infect a novel species may adapt to this species and change their behaviour, meaning they can become more or less aggressive and/ or more or less transmissible. There is concern that Ebolaviruses may adapt to humans during human outbreaks, which may result in the emergence of novel virus types that can more easily spread between humans. Established in 1965, the University of Kent - the UK's European university - now has almost 20,000 students across campuses or study centres at Canterbury, Medway, Tonbridge, Brussels, Paris, Athens and Rome. It has been ranked: third for overall student satisfaction in the 2014 National Student Survey; 16th in the Guardian University Guide 2016; 23rd in the Times and Sunday Times University Guide 2016; and 22nd in the Complete University Guide 2015. In the Times Higher Education (THE) World University Rankings 2015-16, Kent is in the top 10% of the world's leading universities for international outlook. Kent is ranked 17th in the UK for research intensity (REF 2014). It has world-leading research in all subjects and 97% of its research is deemed by the REF to be of international quality. Along with the universities of East Anglia and Essex, Kent is a member of the Eastern Arc Research Consortium (http://www. ). The University is worth £0.7 billion to the economy of the south east and supports more than 7,800 jobs in the region. Student off-campus spend contributes £293.3m and 2,532 full-time-equivalent jobs to those totals. In 2014, Kent received its second Queen's Anniversary Prize for Higher and Further Education.


Kurzlehrgang mit Fokus auf Assay zum Nachweis von intrazellulären Zytokinen bei adoptiven Zelltherapie-Studien, Poster legt metaproteomische Analyse des Darm-Mikrobioms bei Säuglingen dar Wie Caprion Biosciences Inc. heute bekanntgab, wird Dr. Yoav Peretz, Scientific Director bei ImmuneCarta, einen Kurzlehrgang zu neuartigen Methoden in der Entwicklung von Assays zum Nachweis intrazellulärer Zytokine bei adoptiven Zelltherapie-Studien im Rahmen der jährlich stattfindenden Molecular Medicine Triconference in San Francisco (Kalifornien) leiten.  Der Kurs konzentriert sich auf die Bereitstellung von Leitlinien für Nachweis, Persistenz und phänotypische Charakterisierung von Pentamer CD8+ T-Zellen bei adoptiven zellulären Immuntherapie-Studien. Caprion wird außerdem ein Poster zu einer explorativen Studie für die Ausforschung einer metaproteomischen Analyse des fäkalen Mikrobioms bei Säuglingen präsentieren.  Ziel der Studie war die Erstellung einer Taxonomie zum Darm-Mikrobiom und die Erhebung von Funktionsdaten aus Fäkalproben in einer Säuglingspopulation. Die Ergebnisse belegen, dass der proteomische Ansatz funktionelle Änderungen und Reaktionen mit deutlich größerer Abdeckung von Bakterien-Gattungen als eine Herangehensweise über Pyrosequenzierung liefert. Die Signalweganalyse arbeitet auch die Unterschiede zwischen individuellen Mikrobiomen heraus und bietet Einblicke in ihre funktionellen Reaktionen hinsichtlich Ernährung, Erkrankung und Therapie. Kurzlehrgang: Development and Deployment of an Intracellular Cytokine Detection Assay in Adoptive Cell Therapy Trials (Entwicklung und Einsatz eines Assays zum Nachweis intrazellulärer Zytokine bei adoptiven Zelltherapie-Studien)   SC24 "Flow Cytometry and Phenotypic Cell Analysis in Immuno-Oncology" ("Durchflusszytometrie und phänotypische Zellanalyse in der Immunonkologie") Referent: Yoav Peretz, PhD, Scientific Director, ImmuneCarta Montag, 20. Februar, 10:10 Uhr Poster-Präsentation im Rahmen der Konferenz "Metaproteomic Analysis of the Infant Fecal Microbiome" ("Metaproteomische Analyse des fäkalen Mikrobioms bei Säuglingen") Laetitia Cortes[1], Aude Tartière[1], Julie Piquenot[1], Sebastian Tims[2], Joost W. Gouw[2], Jan Knol[2],[3], Harm Wopereis[2],[3] und Daniel Chelsky[1] [1]Caprion Biosciences Inc, Montreal, Canada; [2]Nutricia Research, Utrecht, Niederlande; [3]Universität Wageningen, Labor für Mikrobiologie, Wageningen, Niederlande Informationen zu Caprion Biosciences, Inc. Caprion stellt als führender Anbieter Proteomik und Immunüberwachungsdienste für die Pharma- und Biotechnologiebranche bereit. Caprions Geschäftsbereich ImmuneCarta® widmet sich der Immunüberwachung und liefert proprietäre multiparametrische Durchflusszytometrie für funktionale Analysen des angeborenen und erworbenen Immunsystems. Caprions Proteomik-Division, ProteoCarta™, bietet proprietäre gelfreie, markierungsfreie Massenspektrometrie (MS), die der umfassenden, quantitativen und robusten Vergleichsmessung von Proteinen in umfangreichen biologischen Probensets für die Entdeckung und Validierung von Proteinbiomarkern dient. Das in Montreal (Kanada) und Belgien ansässige Caprion stellt seit mehr als 15 Jahren großangelegte Proteomik- und Immunmonitoring-Dienste für mehr als 50 große Pharma- und Biotech-Kunden bereit. Caprion ist ein Privatunternehmen, das sich im Mehrheitsbesitz von Global Healthcare Opportunities bzw. GHO Capital Partners LLP befindet. Weitere Informationen finden Sie unter http://www.caprion.com.


News Article | February 15, 2017
Site: www.eurekalert.org

WORCESTER, MA - A father's nicotine use may have a significant impact on children's risk of some diseases. In a study published in the online biomedical sciences journal eLife, Oliver J. Rando, MD, PhD, and colleagues at UMass Medical School, demonstrate that mice born of fathers who are habitually exposed to nicotine inherit enhanced chemical tolerance and drug clearance abilities. These findings offer a powerful framework for exploring how information about a father's environmental exposure history is passed down to offspring. "Children born of fathers who have been exposed to nicotine are programmed to be not only more resistant to nicotine toxicity, but to other chemicals as well," said Dr. Rando, professor of biochemistry & molecular pharmacology. "If a similar phenomenon occurs in humans, this raises many important questions. For example, if your father smoked does that mean chemotherapy might be less effective for you? Are you more or less likely to smoke? It's important to understand what information is specifically being passed down from father to offspring and how that impacts us." Studies over the past decade in the field of epigenetics - the study of inheritable traits that are carried outside the genome - have provided unexpected support to the notion that the environmental conditions experienced by a parent can affect disease risk and other features of future generations. In mammals, many of these studies have focused on interactions between the male parent and the offspring - paternal effects - as these are in many ways easier to investigate than maternal effects. Specifically, a number of studies have linked paternal diet to metabolic changes in offspring, while others link paternal stress to anxiety-like behaviors in the next generation. Despite the growing number of these studies, only a small number of paternal exposures have been explored rigorously in the lab. In addition, it has remained unclear in these studies whether the offspring response is specific for the paternal exposure, or whether it is a more generic response to a father's overall quality of life. To address this question, Rando and colleagues set out to determine how precise the response is for the environment experienced by the male parent, by looking at a single molecular interaction. Nicotine is a commonly used drug in humans, and acts by binding to a specific molecular receptor. Providing male mice with access to nicotine, researchers sought to learn whether their offspring were more or less sensitive to nicotine, and whether the offspring response was specific to nicotine or extended to other molecules. What researchers found is that the offspring of nicotine-exposed fathers, compared to the offspring of fathers that were never exposed to nicotine, were protected from toxic levels of nicotine. Researchers then tested whether this resistance was specific for nicotine by treating both sets of offspring with cocaine, which acts via a wholly distinct molecular pathway than nicotine. Surprisingly, the children of nicotine-exposed fathers were also protected from cocaine. This multi-toxin resistance is likely a result of enhanced drug metabolism in the liver, and corresponds to an increase in expression levels of genes involved in drug metabolism. These genes were also packaged in a more open and accessible configuration in the liver cells, allowing for increased expression. "This demonstrates that 'dad' paints with very broad brush strokes. Fathers exposed to nicotine do not specifically program changes in nicotine receptors in their children, as these children are broadly resistant to multiple toxins," said Rando. To determine if multiple, distinct molecules are capable of affecting drug resistance in the next generation, Rando and colleagues treated male mice with another bioactive compound, mecamylamine, which blocks nicotine receptors and is sometimes used to help people stop smoking. Surprisingly, offspring of these mice exhibited the same chemical resistance as those exposed to nicotine. "These findings raise key questions about what drugs or molecules are sufficient to affect children of exposed fathers," said Rando. "What distinguishes nicotine and mecamylamine from the countless small molecules present in our food and environment?" The next step for Rando and colleagues is to determine how many channels of information are being passed down from parent to offspring. "We now know that this information is relatively nonspecific," he said. "But is dad only telling us, on a scale of 1 to 10, that his life was good or not, or is he telling us four or five things broadly about the amount of food, level of stress and degree of chemical exposure?" Given the prevalence of smoking in humans, Rando notes that "there are obvious reasons to be interested in whether this type of effect also happens in human beings, but given the differences between mice and humans in their metabolism of nicotine, it will need to be tested rigorously in future studies of human populations." The University of Massachusetts Medical School (UMMS), one of five campuses of the University system, is comprised of the School of Medicine, the Graduate School of Biomedical Sciences, the Graduate School of Nursing, a thriving research enterprise and an innovative public service initiative, Commonwealth Medicine. Its mission is to advance the health of the people of the Commonwealth through pioneering education, research, public service and health care delivery with its clinical partner, UMass Memorial Health Care. In doing so, it has built a reputation as a world-class research institution and as a leader in primary care education. The Medical School attracts more than $266 million annually in research funding, placing it among the top 50 medical schools in the nation. In 2006, UMMS's Craig C. Mello, PhD, Howard Hughes Medical Institute Investigator and the Blais University Chair in Molecular Medicine, was awarded the Nobel Prize in Physiology or Medicine, along with colleague Andrew Z. Fire, PhD, of Stanford University, for their discoveries related to RNA interference (RNAi). The 2013 opening of the Albert Sherman Center ushered in a new era of biomedical research and education on campus. Designed to maximize collaboration across fields, the Sherman Center is home to scientists pursuing novel research in emerging scientific fields with the goal of translating new discoveries into innovative therapies for human diseases.


News Article | February 15, 2017
Site: phys.org

Ebola is one of the world's most virulent diseases, though rodent species such as guinea pigs, rats and mice are not normally susceptible to it. However, through repeated infection of a host animal, Ebola virus strains can be generated that replicate and cause disease within new host rodent species. Scientists in the University of Kent's School of Biosciences examined the changes associated with Ebolavirus adaptation to rodents including guinea pigs and mice across four different studies. They found that only very few mutations, probably fewer than five, are required for the virus to adapt. In particular, a change in the Ebolavirus protein VP24 seems to be critical for Ebola viruses to infect a new animal species. Ebolaviruses infecting domestic species, including pigs and dogs, may also result in virus changes that may increase the risk to humans. Reston viruses, Ebolaviruses that have not been shown to cause disease in humans, so far, are known to circulate in domestic pigs in Asia. The research was performed by Dr Mark Wass (Senior Lecturer in Computational Biology), Professor Martin Michaelis (Professor of Molecular Medicine), and Dr Jeremy Rossman (Senior Lecturer in Virology) and members of their research groups. The research, entitled Changes associated with Ebola virus adaptation to novel species, was published in the journal Bioinformatics. Explore further: Research shows potential for emergence of new Ebola virus that causes disease in humans


News Article | February 16, 2017
Site: www.sciencedaily.com

Kent researchers have identified how few mutations it can take for Ebolaviruses to adapt to affect previously resistant species. Ebola is one of the world's most virulent diseases, though rodent species such as guinea pigs, rats and mice are not normally susceptible to it. However, through repeated infection of a host animal, Ebola virus strains can be generated that replicate and cause disease within new host rodent species. Scientists in the University of Kent's School of Biosciences examined the changes associated with Ebolavirus adaptation to rodents including guinea pigs and mice across four different studies. They found that only very few mutations, probably fewer than five, are required for the virus to adapt. In particular, a change in the Ebolavirus protein VP24 seems to be critical for Ebola viruses to infect a new animal species. Ebolaviruses infecting domestic species, including pigs and dogs, may also result in virus changes that may increase the risk to humans. Reston viruses, Ebolaviruses that have not been shown to cause disease in humans, so far, are known to circulate in domestic pigs in Asia. The research was performed by Dr Mark Wass (Senior Lecturer in Computational Biology), Professor Martin Michaelis (Professor of Molecular Medicine), and Dr Jeremy Rossman (Senior Lecturer in Virology) and members of their research groups. The research, entitled "Changes associated with Ebola virus adaptation to novel species," was published in the journal Bioinformatics.


News Article | February 1, 2017
Site: www.medicalnewstoday.com

The wear and tear of life takes a cumulative toll on our bodies. Our organs gradually stiffen through fibrosis, which is a process that deposits tough collagen in our body tissue. Fibrosis happens little by little, each time we experience illness or injury. Eventually, this causes our health to decline. "As we age, we typically accumulate more fibrosis and our organs become dysfunctional," says Denisa Wagner, PhD, the Edwin Cohn Professor of Pediatrics in the Program in Cellular and Molecular Medicine and a member of the Division of Hematology/Oncology at Boston Children's Hospital and Harvard Medical School. Ironically, fibrosis can stem from our own immune system's attempt to defend us during injury, stress-related illness, environmental factors and even common infections. But a Boston Children's team of scientists thinks preventative therapies could be on the horizon. A study by Wagner and her team, published recently by the Journal of Experimental Medicine, pinpoints a gene responsible for fibrosis and identifies some possible therapeutic solutions. "We've documented in mice how deletion of a single gene, PAD4, has a drastic effect on curbing the complex process of fibrosis," says Kim Martinod, PhD, a former postdoctoral fellow and co-lead author on the study with Thilo Witsch, MD, and Luise Erpenbeck, MD, in Wagner's lab. Their research indicates that an already-FDA-approved drug used by cystic fibrosis patients could shield our organs from fibrosis during acute events, like lung infection or heart attack. And looking to the future, they envision that the development of a once-daily pill, capable of inhibiting PAD4, could one day be used as a preventative measure. The PAD4 gene controls an enzyme of the same name. In times of infection or bodily stress, the PAD4 enzyme activates a strange, primitive immune defense that ends up doing more harm than good. White blood cells, called neutrophils, self-combust and eject their own DNA strands outward like javelins. Sacrificing themselves, the exploded neutrophils and their outreaching DNA tentacles form so-called neutrophil extracellular traps (NETs), which nature perhaps intended to use as webs for catching foreign invaders and plugging up injury-related bleeding. Even though NETs try to help us, they counteractively set off a chain reaction that deposits an insidious type of collagen amidst our organs' hard-working cells. This collagen-laced fibrosis keeps piling up each time our body's immune system releases NETs. Over a lifetime, cumulative fibrosis is a far more important factor in health than any possible benefits imparted by NET release. "Suppressing PAD4 activity and therefore blocking NET formation over the course of someone's lifetime could potentially have dramatic effects on overall organ function, we hypothesized," says Wagner. Wagner's team set out to demonstrate the relationship between PAD4, NET release, aging and organ fibrosis. They studied mice, which share very similar immune responses with humans. Whereas young hearts in mice and humans contain thin layers of connective tissue, older hearts typically have too much connective collagen built up between heart muscle cells. This reduces the heart's ability to pump blood efficiently. To investigate PAD4's effects on age-related cardiac fibrosis, Wagner's team compared heart tissue of normal mice with another group of mice that had the PAD4 gene deleted. They observed that old mice without PAD4 had much less fibrosis than the normal mice. In fact, these mice had heart tissue that looked strikingly similar to heart tissue of young mice, and they kept up remarkably "young" levels of systolic and diastolic heart function as they aged. Wagner's team then looked at collagen deposition in mouse lungs. They found that deleting the PAD4 gene also significantly reduced lung fibrosis as mice aged. The researchers believe these observations show that deleting the PAD4 gene in mice protected their organs from age-related fibrosis and dysfunction. "If we could inhibit PAD4 or otherwise stop NET release in humans, we might be able to greatly reduce age-related fibrosis and improve our quality of life," says Wagner. For starters, it turns out there's already a drug on the market that can degrade NETs after they've been released. It works by targeting the expelled strands of DNA that characterize NETs. The DNA-destroying enzyme DNase has been developed into a drug used today by cystic fibrosis (CF) patients. CF makes the body's fluid secretions very thick, causing mucus accumulation and frequent lung infection. In the face of the ensuing infection, PAD4 activates prolific NET release in CF patients' lungs. Together with bacteria, this forms a gel-like layer of debris that further debilitates the lungs. To combat this gel, CF patients turn to an inhalable drug form of DNase. "NETs are easily targeted and destroyed by DNase in the lungs of CF patients," says Wagner. "So by extending DNase use to a much wider range of patients experiencing infectious illness or injury, we could potentially clear up NETs elsewhere in the body and prevent subsequent organ fibrosis." Wagner's team tested this approach in an experimental model of mice with cardiac injury leading to heart failure, which activates the PAD4 enzyme and triggers NET release. Within one month, fibrosis and decline in heart function will typically follow. Interestingly, mice that received DNase injections in the next few days after cardiac injury were protected from fibrosis nearly as well as mice that had their PAD4 gene deleted (and therefore never experienced NET release at all). DNase might therefore be a powerful interventional therapy. It could potentially fight off accumulating organ fibrosis caused by a huge variety of infections or acute injuries. To block NET release before it can even happen, Wagner and her team envision a PAD4 inhibitor drug that could stop neutrophils from being activated by the PAD4 enzyme. "The development of orally-administered PAD4 inhibitors intended to be taken like baby aspirin could radically improve our quality of life as we age," Wagner speculates.


News Article | February 15, 2017
Site: news.europawire.eu

STOCKHOLM, 14-Feb-2017 — /EuropaWire/ — A new study from Karolinska Institutet shows that short-course preoperative radiotherapy combined with delayed surgery reduces the adverse side-effects of rectal cancer surgery without compromising its efficacy. The results are presented in the journal The Lancet Oncology. Rectal cancer affects some 2,000 men and women in Sweden every year. Preoperative radiotherapy was gradually introduced in the early 1990s, with a consequent improvement in prognosis for people with rectal cancer and reduction in the risk of local recurrence. “Back then we showed that preoperative radiotherapy reduces the risk of local recurrence by over 50 per cent for patients with rectal cancer,” says principal investigator Anna Martling, senior consultant surgeon and professor at Karolinska Institutet’s Department of Molecular Medicine and Surgery. “Thanks to our results, radiotherapy is recommended to many rectal cancer patients.” However, radiotherapy can cause adverse reactions and the optimal radiotherapeutic method and the interval between it and the ensuing surgery have been mooted. The study now presented in The Lancet Oncology is based on the claim that the adverse effects of rectal cancer treatment can be reduced by administering more but lower doses of radiation for a longer time, or by increasing the interval between radiotherapy and surgery. These hypotheses have now been tested in a study in which rectal cancer patients were randomly assigned to three different treatment arms: The results of the study show that patients with delayed surgery develop fewer complications with equally good oncological outcomes. It also showed that there is no difference between long-course and short-course radiotherapy other than that the former considerably lengthens the time for treatment. “The results of the study will give rise to improved therapeutic strategies, fewer complications with a sustained low incidence of local recurrence, and better survival rates for rectal cancer patients,” says Professor Martling. “The results can now be immediately put to clinical use to the considerable benefit of the patients.” Eighteen Swedish hospitals took part in the study, which was financed by the Swedish Research Council and the Cancer Society in Stockholm, and through the regional ALF agreement between Stockholm County Council and Karolinska Institutet. Researchers from the universities in Lund, Uppsala and Linköping also contributed to findings. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial Johan Erlandsson, Torbjörn Holm, David Pettersson, Åke Berglund, Björn Cedermark, Calin Radu, Hemming Johansson, Mikael Machado, Fredrik Hjern, Olof Hallböök, Ingvar Syk, Bengt Glimelius, Anna Martling The Lancet Oncology, online 9 February 2017, DOI: http://dx.doi.org/10.1016/S1470-2045(17)30086-4

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