News Article | May 30, 2017
Dr. Ravetch will receive the Feinstein Institute for Medical Research and Molecular Medicine's 2017 Award for his research in immunology NEW YORK, May 30, 2017 - The New York Academy of Sciences in conjunction with the Feinstein Institute for Medical Research and Molecular Medicine will host the 2017 Ross Prize in Molecular Medicine - Regulating Immunity: Fc Receptor Biology at the Academy's headquarters on Monday, June 5th. Pioneering immunology researcher Jeffrey V. Ravetch MD, PhD, the Theresa and Eugene M. Lang Professor and Head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at The Rockefeller University, will be awarded this year's prize, which includes a $50,000 award for his identification of the mechanism by which the specific structure of antibodies controls immune cell reactivity. "I am honored by the recognition this award represents and to be included among the distinguished scientists who have preceded me," said Dr. Ravetch on the news of his receiving the award. Dr. Ravetch's research focuses on understanding the immune system response. His work revealed the fine line that exists between healthy immune reactions that destroy foreign pathogens, and autoimmunity that attacks the body's own tissue. This understanding and improved knowledge of immunity will allow for the improvement or creation of new therapies for infectious, neoplastic, and inflammatory diseases. The Ross Prize recognizes biomedical scientists who have made a significant impact in the understanding of human disease pathogenesis and/or treatment, and who hold significant promise for making even greater contributions to the general field of molecular medicine. "Dr. Jeffrey Ravetch's discovery of the relationship between antibodies and activation of the immune response has opened the door to developing new therapies for autoimmune conditions," said Feinstein Institute President and CEO Kevin J. Tracey, MD, who also serves as editor emeritus of Molecular Medicine. "His work embodies the pioneering spirit of the Ross Prize and we look forward to honoring his career and to his future discoveries' positive impact on patients." After the presentation ceremony, Dr. Ravetch will give a lecture titled, "Diversification of Antibody Effector Function," where he will discuss his findings in the field of Fc Receptor Biology. In addition, Rafi Ahmed, PhD, Director of the Emory Vaccine Center, and Ronald Levy, MD, Professor and Chief of the Division of Oncology at Stanford Medicine, will discuss their work on antibody dependent mechanisms of protection in infectious disease and cancer. If you are interested in attending this event in person please visit the registration page for additional information. The Feinstein Institute for Medical Research is the research arm of Northwell Health, the largest healthcare provider in New York. Home to 50 research laboratories and to clinical research throughout dozens of hospitals and outpatient facilities, the 3,500 researchers and staff of the Feinstein are making breakthroughs in molecular medicine, genetics, oncology, brain research, mental health, autoimmunity, and bioelectronic medicine - a new field of science that has the potential to revolutionize medicine. For more information about how we empower imagination and pioneer discovery, visit FeinsteinInstitute.org Molecular Medicine is an Open-Access, international, peer-reviewed, biomedical journal seeking insight into the cellular and molecular basis of disease. The journal publishes work in the format of original research articles, review articles, editorials, commentaries and letters to the editor. The 2014 Journal Citation Report (JCR) lists Molecular Medicine with an impact factor of 4.508. For more information, visit http://www. . The New York Academy of Sciences is an independent, not-for-profit organization that since 1817 has been driving innovative solutions to society's challenges by advancing scientific research, education, and policy. With more than 20,000 Members in 100 countries, the Academy is creating a global community of science for the benefit of humanity. Please visit us online at http://www. and follow us on Twitter at @NYASciences.
News Article | May 28, 2017
AIIMS and CSIR IGIB Ink Deal for Partnership in Clinical and Translational Genomics, Expanding on Reach of the GUaRDIAN Programme The All India Institute of Medical Sciences (AIIMS) Delhi and CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB) inked a deal for collaborative research in the area of Rare Diseases and application of genomics to aid clinical decisions, expanding on the reach of the GUaRDIAN programme. New Delhi, India, May 28, 2017 --( AIIMS Delhi is a premier Institute for medical education and research in India, having extraordinary infrastructure, specialized medical/paramedical staff, management and state of the art facilities for patient care, training programmes and research activities. CSIR-IGIB is one of the premier Institutes in India pioneering cutting edge advancements in Genomic Science and a constituent laboratory of the Council for Scientific and Industrial Research (CSIR). Research at CSIR-IGIB spans a variety of areas including Genomics & Molecular Medicine, Chemical & Systems Biology, Genome Informatics & Structural Biology, Respiratory Disease Biology and Energy & Environmental Biotechnology. As part of the agreement, AIIMS Delhi and CSIR IGIB would collaborate in the area of genetic diseases as well as application of genomics in clinical settings. This would include formulation and participation in joint collaborative programs spanning genomics for aiding the diagnosis, understanding the prognosis and aiding precise therapy of genetic diseases. The deal would also enable faculty members of both institutes to actively participate in formulating and implementing collaborative programs aimed at accelerating the application of genomics to aid clinical decisions. The deal would also allow AIIMS Delhi to access the state of the art genomics and bioinformatics infrastructure as well as the clinical genomics analytical resources at CSIR IGIB to enable fast, accurate and cost effective diagnosis of genetic diseases for patients coming to AIIMS Delhi. CSIR IGIB has been a pioneer in translational genomics in India. The Genomics for Understanding Rare Diseases India Alliance Network (GUaRDIAN) is a focussed translational research programme in the area of Rare Diseases initiated in the year 2015. The programme has evolved to become one of the largest of its kind in the area of Rare genetic diseases with a clinical collaborative network of over 100 clinicians from over 35 clinical centres across India working on Rare Diseases. A complementary programme entitled Genomics and other Omics tools for Enabling Medical Decisions (GOMED) initiated last year at CSIR IGIB enables affordable and equitable access to genetic diagnosis. The programme covers genetic tests for over 80 genes and has already catered to over 2000 patients in from over 25 Centres from across India. Skilled manpower is undoubtedly essential to advance and accelerate clinical adoption of genomics. This deal also envisages imparting genomics knowledge for practicing clinicians through training and education as well as faculty exchange. This would surely provide impetus to national initiatives like the Skill India programme. The deal also envisages setting up collaborative research programmes aimed at accelerating research in the area of clinical genomics in India. New Delhi, India, May 28, 2017 --( PR.com )-- The All India Institute of Medical Sciences (AIIMS) Delhi and CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB) inked a deal for collaborative research in the area of Rare Diseases and application of genomics to aid clinical decisions.AIIMS Delhi is a premier Institute for medical education and research in India, having extraordinary infrastructure, specialized medical/paramedical staff, management and state of the art facilities for patient care, training programmes and research activities. CSIR-IGIB is one of the premier Institutes in India pioneering cutting edge advancements in Genomic Science and a constituent laboratory of the Council for Scientific and Industrial Research (CSIR). Research at CSIR-IGIB spans a variety of areas including Genomics & Molecular Medicine, Chemical & Systems Biology, Genome Informatics & Structural Biology, Respiratory Disease Biology and Energy & Environmental Biotechnology.As part of the agreement, AIIMS Delhi and CSIR IGIB would collaborate in the area of genetic diseases as well as application of genomics in clinical settings. This would include formulation and participation in joint collaborative programs spanning genomics for aiding the diagnosis, understanding the prognosis and aiding precise therapy of genetic diseases. The deal would also enable faculty members of both institutes to actively participate in formulating and implementing collaborative programs aimed at accelerating the application of genomics to aid clinical decisions.The deal would also allow AIIMS Delhi to access the state of the art genomics and bioinformatics infrastructure as well as the clinical genomics analytical resources at CSIR IGIB to enable fast, accurate and cost effective diagnosis of genetic diseases for patients coming to AIIMS Delhi.CSIR IGIB has been a pioneer in translational genomics in India. The Genomics for Understanding Rare Diseases India Alliance Network (GUaRDIAN) is a focussed translational research programme in the area of Rare Diseases initiated in the year 2015. The programme has evolved to become one of the largest of its kind in the area of Rare genetic diseases with a clinical collaborative network of over 100 clinicians from over 35 clinical centres across India working on Rare Diseases.A complementary programme entitled Genomics and other Omics tools for Enabling Medical Decisions (GOMED) initiated last year at CSIR IGIB enables affordable and equitable access to genetic diagnosis. The programme covers genetic tests for over 80 genes and has already catered to over 2000 patients in from over 25 Centres from across India.Skilled manpower is undoubtedly essential to advance and accelerate clinical adoption of genomics. This deal also envisages imparting genomics knowledge for practicing clinicians through training and education as well as faculty exchange. This would surely provide impetus to national initiatives like the Skill India programme. The deal also envisages setting up collaborative research programmes aimed at accelerating research in the area of clinical genomics in India.
News Article | May 25, 2017
ATLANTA -- Dr. Ming-Hui Zou, director of the Center for Molecular & Translational Medicine and a Georgia Research Alliance Eminent Scholar in Molecular Medicine, has renewed a four-year, $2.3 million federal grant to study the role of an enzyme in causing diabetic vascular diseases and the molecular mechanism that leads to these diseases. This is the third competitive renewal for this grant from the National Heart, Lung and Blood Institute of the National Institutes of Health. The diabetes-related research was initially funded in 2005. Diabetes is the seventh leading cause of death in the United States. About 29.1 million Americans, one out of every 11 people, have diabetes, a disease in which blood glucose levels are above normal. Diabetes can cause serious health complications, including heart disease, blindness, kidney failure and lower-extremity amputations, according to the Centers for Disease Control and Prevention. The grant will help Zou determine if adenosine monophosphate-activated protein kinase (AMPK), an essential energy and redox homeostasis sensor, maintains the balance of mitochondrial fission and fusion by promoting the autophagic degradation (the natural, destructive mechanism of the cell that gets rid of unnecessary or dysfunctional components) of dynamin-related protein 1 (DRP1). The findings could lead to a new treatment for diabetic vascular diseases. Mitochondria are the power houses of cells, and a disruption in the balance between mitochondrial fusion and fission is associated with mitochondrial dysfunction in a variety of diseases, including neurodegenerative and cardiovascular diseases. Zou's preliminary data found that inhibiting AMPK is accompanied by increases in mitochondrial fission, oxidative stress and endothelial dysfunction. "The completion of this study will assess whether the inhibition of mitochondrial fission, a crucial step in the initiation of cardiovascular disease, can be a new strategy to protect against the development of vascular disease in diabetic patients," Zou said. The project has two aims. Zou's research team will determine the essential role of AMPK in maintaining the balance between mitochondrial fission and fusion, and they will explain the molecular mechanisms by which AMPK inhibits DRP-1-dependent mitochondrial fission in endothelial cells, which line the inner walls of blood vessels and lymphatic vessels. The studies will be conducted in mice. An abstract of the grant, 5R01HL080499-12, is available at NIH's Project RePORTer website. For more information about the Center for Molecular & Translational Medicine, visit http://medicine. .
News Article | May 24, 2017
Dr. Nurse's monograph on the identification of molecules that control cell division and their implications in cancer treatment will be published in Molecular Medicine MANHASSET, NY - Northwell Health's Feinstein Institute for Medical Research and Molecular Medicine announced today that the seventh Anthony Cerami Award in Translational Medicine will be awarded to Sir Paul Nurse, PhD, director of The Francis Crick Institute. The award is in recognition of his research, which identified protein molecules that control the division (duplication) of cells in the cell cycle currently being examined as a therapy to stop or prevent cancer cell growth. Dr. Nurse's research led to the critical discovery that the protein, cyclin-dependent protein kinase (CDK), found both in yeast and in human genes, controls the cell cycle or cell growth process. Knowledge of the cell cycle is critical to the treatment of cancer. Most cancers are caused by the uncontrolled cell division due to damage to the controls regulating cell growth and reproduction, or by damage to how the cell replicates and grows. Leading drug companies are utilizing the understanding of the role that CDK plays in cell growth to test new therapies to stop cancer cell growth. "The Anthony Cerami Award in Translational Medicine was established to recognize investigators who provide the crucial early knowledge that inspires further research and leads to new therapies," said Kevin J. Tracey, MD, president and CEO of the Feinstein Institute, editor emeritus of Molecular Medicine, and Cerami Award committee member. "Dr. Nurse's discovery of CDK is a fundamental advance that is now helping the development of targeted treatments for cancer." The Cerami Award, which includes a $20,000 prize, is conferred semi-annually by the editors of Molecular Medicine, a peer-reviewed, open-access journal published by the Feinstein Institute. A monograph authored by Dr. Nurse titled, "A Journey in Science: Cell Cycle Control," has been published on the Molecular Medicine website. "It is an honor to be recognized as an Anthony Cerami Award winner for my work on CDK and its impact on cancer," said Dr. Nurse. "When deciding on a course of study, it has been my belief that it is essential to tackle a significant research problem, one that if solved could make a difference. I'm happy to tell my story to inspire investigators on their path to making a difference." The Feinstein Institute is committed to celebrating the stewardship of the scientific process and imparting that perspective to young scientists. It also recognizes that the story behind making a discovery in medicine or health care should be cherished and broadly shared. The goal of the Cerami Award and its associated monographs is to document the thinking leading to such innovations and discoveries so that these stories can endure and inspire future generations of investigators. The Anthony Cerami Award in Translational Medicine was made possible by the generosity of Dr. Cerami and the Ann Dunne Foundation for World Health. Dr. Cerami's breakthrough translational work includes the identification of anti-TNF's potential to treat a number of inflammatory diseases, including rheumatoid arthritis, and the development of the HbA1c Diagnostic Test, currently the gold standard for the diagnosis and control of diabetes. He is currently working on a potential treatment of diabetes as CEO of Araim Pharmaceuticals. Molecular Medicine is an open access, international, peer-reviewed biomedical journal published by The Feinstein Institute for Medical Research. Molecular Medicine promotes the understanding of normal body functioning and disease pathogenesis at the cellular and molecular levels, allowing researchers and physician-scientists to use that knowledge in the design of specific tools for disease diagnosis, treatment, prognosis, and prevention. For more information, visit molmed.org. The Feinstein Institute for Medical Research is the research arm of Northwell Health, the largest healthcare provider in New York. Home to 50 research laboratories and to clinical research throughout dozens of hospitals and outpatient facilities, the 3,500 researchers and staff of the Feinstein are making breakthroughs in molecular medicine, genetics, oncology, brain research, mental health, autoimmunity, and bioelectronic medicine - a new field of science that has the potential to revolutionize medicine. For more information about how we empower imagination and pioneer discovery, visit FeinsteinInstitute.org
News Article | May 8, 2017
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.
News Article | May 8, 2017
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
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 16, 2017
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
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
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