News Article | January 6, 2016
"Our creation of a Cas9 variant that brings off-target effects to levels where we can no longer detect them, even with the most sensitive methods, provides a substantial advance for therapeutic applications in which you want to accurately hit your target without causing damage anywhere else in the genome," says J. Keith Joung, MD, PhD, associate chief for Research and the Jim and Ann Orr MGH Research Scholar in the MGH Department of Pathology, senior author of the Nature paper. "But its impact will also be incredibly important for research applications because off-target effects can potentially confound the results of any experiment. As a result, we envision that our high-fidelity variant will supplant the use of standard Cas9 for many research and therapeutic applications." Used to create targeted DNA breaks at which genetic changes can be introduced, CRISPR-Cas9 nucleases combine a bacterial DNA-cutting enzyme called Cas9 with a short guide RNA sequence that can bind to the target DNA sequence. While easier to use than previous gene-editing tools, CRISPR-Cas9 nucleases have a well-characterized and significant limitation. As described in 2013 studies led by Joung and others, CRISPR-Cas9 nucleases can induce off-target DNA breaks at sites that resemble the on-target sequence. Subsequent investigations by Joung's team and others have reduced but never completely and consistently eliminated these off-target effects. Joung and his colleagues hypothesized that reducing interactions between Cas9 and the target DNA might more completely eliminate off-target effects while still retaining the desired on-target interaction. The MGH team focused on the fact that certain portions of the Cas9 enzyme itself can interact with the backbone of the target DNA molecule. Pursuing an observation originally made by co-lead author Vikram Pattanayak, MD, PhD, of MGH Pathology, the team altered four of these Cas9-mediated contacts by replacing the long amino acid side-chains that bind to the DNA backbone with shorter ones unable to make those connections. "Our previous work suggested that Cas9 might bind to its intended target DNA site with more energy than it needs, enabling unwanted cleavage of imperfectly matched off-target sites," says Pattanayak. "We reasoned that, by making substitutions at these four positions, we could remove some of that energy to eliminate off-target effects while still retaining full on-target activities." Co-lead author Benjamin Kleinstiver, PhD, of the MGH Molecular Pathology Unit and Michelle Prew, a research technician in Joung's lab, then tested all 15 possible variants in which any combination of one, two, three or four of those amino acid side-chains were altered and found that one three-substitution and one four-substitution variant appeared to show the greatest promise in discriminating against mismatched target sites while retaining full on-target activities in human cells. The researchers then more fully characterized the four-substitution variant, which they called SpCas9-HF1 (Sp for the Streptococcus pyogenes bacteria, which is the source of this widely used Cas9, and HF for high-fidelity). They found that this variant induced on-target effects comparable to those observed with the original unaltered SpCas9 when used with more than 85 percent of 37 different guide RNAs they tested. Using GUIDE-Seq, a highly sensitive system Joung's lab developed in 2014 to detect off-target CRISPR-Cas9 effects across the genome, the team found that, while nucleases combining unaltered SpCas9 with seven different guide RNAs induced as many as 25 off-target mutations, use of SpCas9-HF1 produced no detectable off-target effects with six of those guide RNAs and only one off-target site with the seventh. These results were further confirmed using targeted deep-sequencing experiments. Joung's team also found that SpCas9-HF1 could reduce off-target effects when targeting atypical DNA sites characterized by repeat sequences of one or two nucleotides - sites that are typically subject to many off-target mutations. They developed additional derivatives of SpCas9-HF1 - called HF2, HF3 and HF4 - which could eliminate the few residual off-target effects that persisted with the HF1 variant and a small number of guide RNAs. "If SpCas9-HF1 using a certain guide RNA still produces a handful of off-target effects that are particularly difficult to eliminate, it may be possible to engineer new variants that get rid of even those effects," says Joung, who is a professor of Pathology at Harvard Medical School. The researchers also showed that SpCas9-HF1, like its naturally occurring counterpart, could be combined with other useful alterations that extend its utility. Previous work from the Joung lab published last summer in Nature had shown that introducing a series of amino acid substitutions could expand the targeting range of unaltered SpCas9. In the current study, the authors show that introducing these same alterations into SpCas9-HF1 also extended the targeting range of the high-fidelity variant. "These results show that these variants should be broadly useful to anyone currently using CRISPR-Cas9 technology," says Kleinstiver. "They can easily be used in place of wild-type SpCas9 and provide a highly effective method for reducing off-target mutations to undetectable levels." Explore further: New genome-editing platform significantly increases accuracy of CRISPR-based systems More information: Benjamin P. Kleinstiver et al. High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects, Nature (2016). DOI: 10.1038/nature16526
News Article | November 3, 2016
FAIRPORT, NY, November 03, 2016-- William Y. Chey, MD, DSc, has been included in Marquis Who's Who. As in all Marquis Who's Who biographical volumes, individuals profiled are selected on the basis of current reference value. Factors such as position, noteworthy accomplishments, visibility, and prominence in a field are all taken into account during the selection process.With more than 50 years of experience as a physician, educator and research scientist in gastrointestinal medicine, Dr. Chey is widely recognized for his expertise in the field of gastroenterology and hepatology. Prior to his retirement in 2000, he served as a professor of medicine and director of the Division of Gastroenterology and Hepatology at the University of Rochester Medical Center, and as a consultant gastroenterologist at Canandaigua VA Medical Center. He is a fellow of the American College of Gastroenterology and the American Gastroenterological Association, a member of the AGA Legacy Society, and was a member of the American Association for the Advancement of Science and American Physiological Society, among other medical organizations. In addition, he is the former president of the American Pancreatic Association and the American Society of Acupuncture. He was invited nationally and internationally as a visiting professor by numerous prestigious institutions in the United States, Europe, Asia and Mid-Eastern countries. In particular, he holds the titles of Honorary Professor at the Catholic University College of Medicine, Seoul, Korea and Visiting Professor at Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China and Korea University College of Medicine, Seoul, Korea.After completing his medical education in 1953 through the two top medical schools in Seoul, Korea, Seoul National University and Yonsei University in Seoul, Korea, and serving as a medical officer of the Republic of Korea in the Korean War, Dr. Chey emigrated to the United States in 1954 and had his post-graduate training including internship and residency in internal medicine at City Hospital of New York, fellowship in pathology at Mount Sinai Hospital, New York, and fellowship in hepatology at Jersey City Medical Center, Seton Hall University School of Medicine and Dentistry, Jersey City, NJ. Then he received advanced degrees of Master of Science in Gastroenterology in 1962 and Doctor of Science in Medicine in 1966 from the University of Pennsylvania School of Medicine. At Temple University Medical Center and the Samuel S. Fel's Research Institute, Temple University School of Medicine, Philadelphia, PA, he finished a fellowship in gastroenterology and became a faculty member in 1963. He was an Associate Professor of Medicine and Head of Gastrointestinal Research in 1971 when he was recruited by the University of Rochester School of Medicine and Dentistry, Rochester, NY. He was the Founding Director of the Isaac Gordon Center for Digestive Diseases and Nutrition at the Genesee Hospital and Attending Physician at Strong Memorial Hospital, Rochester, NY. In 1992, he became Director of the Division of Gastroenterology and Hepatology at the University of Rochester Medical Center. He was also the Founding Director of the William and Sheila Konar Center for Digestive and Liver Diseases at Strong Memorial Hospital until his retirement in 2000. During his tenure, he trained numerous clinical and research fellows from the United States and abroad, including Asia, Europe, South America, Mid-East and Africa. The majority of them returned to their native countries and are active in their leadership positions. During the following ten years, he enjoyed practicing gastrointestinal medicine at the Rochester Institute for Digestive Diseases and Sciences and was also actively involved in the American Gastroenterological Association and the American Pancreatic Association. He has been married to Fan K. Tang since 1959. They have 4 children; William D. married to Janine Zwiren, Donna married to Dale Hoellrich, Richard married to Maura Bauman, and Laura married to Richard Warren, and 9 grandchildren; Cameron, Brandon (deceased), Samuel, Megen, Russell, Paris, Wyatt, Josephine and LiLi.He contributed numerous articles to competitive scientific journals, and published many chapters in text-books and two books of his specialty and research. He was a member of the editorial board of the Pancreas and American Journal of Physiology, and has been the Editor-In-Chief of Clinical Endoscopy since 2011. He served as an active member of the National Institute of Health, Surgery and Bioengineering Study Section and a consultant to the Gastrointestinal Drug Advisory Committee, Food and Drug Administration, Department of Health and Human Services.In recognition of his contributions to medicine, Dr. Chey received a wide variety of honors and awards. He was the recipient of the V.L. William and Frisca Go Award for Life Time Achievement from the American Pancreatic Association, the Governor's Award for Excellence in Clinical Research from the American College of Gastroenterology, Distinguished Clinician Award and Mentor's Research Scholar Award from the American Gastroenterological Association, Distinguished Service Award from the Rochester Academy of Medicine and American Top Physicians Award in 2008 from the Consumers' Research Council of America. He has been cited in Marquis Who's Who in America, in Medicine and Health Care, in Science and Engineering, and in the World.About Marquis Who's Who :Since 1899, when A. N. Marquis printed the First Edition of Who's Who in America , Marquis Who's Who has chronicled the lives of the most accomplished individuals and innovators from every significant field of endeavor, including politics, business, medicine, law, education, art, religion and entertainment. Today, Who's Who in America remains an essential biographical source for thousands of researchers, journalists, librarians and executive search firms around the world. Marquis now publishes many Who's Who titles, including Who's Who in America , Who's Who in the World , Who's Who in American Law , Who's Who in Medicine and Healthcare , Who's Who in Science and Engineering , and Who's Who in Asia . Marquis publications may be visited at the official Marquis Who's Who website at www.marquiswhoswho.com
News Article | March 1, 2017
CAMBRIDGE, Mass., March 01, 2017 (GLOBE NEWSWIRE) -- Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company developing targeted and immuno-oncology therapeutics, today announced preclinical and clinical data presentations will be made during the 2017 American Association for Cancer Research (AACR) Annual Meeting, being held April 1 - 5, 2017, in Washington, D.C. Data on TRX518 will be presented as an oral presentation in a clinical trials plenary session by Roberta Zappasodi, Ph.D., Parker Institute Scholar and Research Scholar in the Ludwig Collaborative Laboratory at Memorial Sloan Kettering Cancer Center from the lab of Taha Merghoub, Ph.D., Associate Attending Lab Member of the Ludwig Collaborative Laboratory at the Memorial Sloan Kettering Cancer Center and Jedd Wolchok, M.D. Ph.D., Chief of Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center. Abstract Number and Title: #CT018, Intratumor and peripheral Treg modulation as a pharmacodynamic biomarker of the GITR agonist antibody TRX-518 in the first in-human trial Session Title: Immuno-oncology Biomarkers in Clinical Trials Session Date and Time: Sunday Apr 2, 2017 3:28 PM - 3:43 PM Session Location: Hall D-E, Level 2, Washington Convention Center Abstract Number and Title: #369, Therapeutic targeting of the Wnt antagonist DKK1 with a humanized monoclonal antibody in oncology indications Session Title: Cell Growth Signaling Pathways 2 Session Date and Time: Sunday Apr 2, 2017 1:00 PM - 5:00 PM Session Location: Convention Center, Halls A-C, Poster Section 15 About Leap Therapeutics Leap Therapeutics’ (NASDAQ:LPTX) most advanced clinical candidate, DKN-01, is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein. DKN-01 is in clinical trials in patients with gastroesophageal cancer in combination with paclitaxel and in patients with biliary tract cancers in combination with gemcitabine and cisplatin. DKN-01 has demonstrated single agent activity in non-small cell lung cancer patients. Leap’s second clinical candidate, TRX518, is a novel, humanized GITR agonist monoclonal antibody designed to enhance the immune system’s anti-tumor response. For more information about Leap Therapeutics, visit http://www.leaptx.com or our public filings with the SEC that are available via EDGAR at http://www.sec.gov or via http://www.investors.leaptx.com/. Some of the statements in this release are forward looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. These statements relate to future events of Leap’s development of DKN-01, TRX518, and other programs, future expectations, plans and prospects. Although Leap believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. Leap has attempted to identify forward looking statements by terminology including ‘‘believes,’’ ‘‘estimates,’’ ‘‘anticipates,’’ ‘‘expects,’’ ‘‘plans,’’ ‘‘projects,’’ ‘‘intends,’’ ‘‘potential,’’ ‘‘may,’’ ‘‘could,’’ ‘‘might,’’ ‘‘will,’’ ‘‘should,’’ ‘‘approximately’’ or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors. Any forward looking statements contained in this release speak only as of its date. We undertake no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.
News Article | December 20, 2016
DALLAS - Dec. 20, 2016 - UT Southwestern Medical Center researchers have invented a transistor-like threshold sensor that can illuminate cancer tissue, helping surgeons more accurately distinguish cancerous from normal tissue. In this latest study, researchers were able to demonstrate the ability of the nanosensor to illuminate tumor tissue in multiple mouse models. The study is published in Nature Biomedical Engineering. "We synthesized an imaging probe that stays dark in normal tissues but switches on like a light bulb when it reaches solid tumors. The purpose is to allow surgeons to see tumors better during surgery," said senior author Dr. Jinming Gao, Professor of Oncology, Pharmacology and Otolaryngology with the Harold C. Simmons Comprehensive Cancer Center. The nanosensor amplifies pH signals in tumor cells to more accurately distinguish them from normal cells. "Cancer is a very diverse set of diseases, but it does have some universal features. Tumors do not have the same pH as normal tissue. Tumors are acidic, and they secrete acids into the surrounding tissue. It's a very consistent difference and was discovered in the 1920's," said Dr. Baran Sumer, Associate Professor of Otolaryngology, and co-senior author of the study. The researchers hope the improved surgical technology can eventually benefit cancer patients in multiple ways. "This new digital nanosensor-guided surgery potentially has several advantages for patients, including more accurate removal of tumors, and greater preservation of functional normal tissues," said Dr. Sumer. "These advantages can improve both survival and quality of life." For example, this technology may help cancer patients who face side effects such as incontinence after rectal cancer surgery. "The new technology also can potentially assist radiologists by helping them to reduce false rates in imaging, and assist cancer researchers with non-invasive monitoring of drug responses," said Dr. Gao. According to the National Cancer Institute, there are 15.5 million cancer survivors in the U.S., representing 4.8 percent of the population. The number of cancer survivors is projected to increase by 31 percent, to 20.3 million, by 2026. Dr. Sumer and Dr. Gao were joined in this study by Dr. Gang Huang, Instructor of Pharmacology; Dr. Xian-Jin Xie, Professor of Clinical Sciences; Dr. Rolf Brekken, Professor of Surgery and Pharmacology and an Effie Marie Cain Research Scholar; and Dr. Xiankai Sun, Director of Cyclotron and Radiochemistry Program in Department of Radiology and Advanced Imaging Research Center, Associate Professor of Radiology, and holder of the Dr. Jack Krohmer Professorship in Radiation Physics; Dr. Joel Thibodeaux, Assistant Professor of Pathology and Director of Cytopathology, Parkland Memorial Hospital. Additional UT Southwestern researchers who contributed to the study include: Dr. Tian Zhao, Dr. Xinpeng Ma, Mr. Yang Li, Dr. Zhiqiang Lin, Dr. Min Luo, Dr. Yiguang Wang, Mr. Shunchun Yang and Ms. Zhiqun Zeng in the Harold C. Simmons Comprehensive Cancer Center; and Dr. Saleh Ramezani in the Department of Radiology. Dr. Gao and Dr. Sumer are scientific co-founders of OncoNano Medicine, Inc. The authors declare competing financial interests in the full-text of the Nature Biomedical Engineering article. UT Southwestern Medical Center has licensed the technology to OncoNano Medicine and has a financial interest in the research described in the article. Funding for the project includes grants from the Cancer Prevention and Research Institute of Texas. Dr. Gao and Dr. Sumer are investigators for two Academic Research grants and OncoNano Medicine was the recipient of a CPRIT Product Development Research grant. Research reported in this press release was supported by the National Cancer Institute under Award Number R01 CA192221 and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Harold C. Simmons Comprehensive Cancer Center is the only NCI-designated Comprehensive Cancer Center in North Texas and one of just 47 NCI-designated Comprehensive Cancer Centers in the nation. Simmons Cancer Center includes 13 major cancer care programs. In addition, the Center's education and training programs support and develop the next generation of cancer researchers and clinicians. Simmons Cancer Center is among only 30 U.S. cancer research centers to be designated by the NCI as a National Clinical Trials Network Lead Academic Participating Site. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. . To automatically receive news releases from UT Southwestern via email, subscribe at http://www.
News Article | February 15, 2017
A study from Massachusetts General Hospital (MGH) researchers has found that a pattern of gene variants associated with an "apple-shaped" body type, in which weight is deposited around the abdomen, rather than in the hips and thighs, increases the risk for type 2 diabetes and coronary heart disease, as well as the incidence of several cardiovascular risk factors. The report appears in the February 14 issue of JAMA. "People vary in their distribution of body fat - some put fat in their belly, which we call abdominal adiposity, and some in their hips and thighs," says Sekar Kathiresan, MD, director of the MGH Center for Genomic Medicine, associate professor of Medicine at Harvard Medical School, and senior author of the JAMA report. "Abdominal adiposity has been correlated with cardiometabolic disease, but whether it actually has a role in causing those conditions was unknown. We tested whether genetic predisposition to abdominal adiposity was associated with the risk for type 2 diabetes and coronary heart disease and found that the answer was a firm 'yes'." While several observational studies have reported greater incidence of type 2 diabetes and heart disease among individuals with abdominal adiposity, they could not rule out the possibility that lifestyle factors - such as diet, smoking and a lack of exercise - were the actual causes of increased disease risk. It also could have been possible that individuals in the early stages of heart disease might develop abdominal adiposity because of a limited ability to exercise. The current study was designed to determine whether body type really could increase cardiometabolic risk. To answer that question, the research team applied a genetic approach called mendelian randomization, which measures whether inherited gene variants actually cause outcomes such as the development of a disease. Using data from a previous study that identified 48 gene variants associated with waist-to-hip ratio adjusted for body mass index - an established measure for abdominal adiposity - they developed a genetic risk score. They then applied that score to data from six major genome-wide association studies and to individual data from the U.K. Biobank - a total research group of more than 400,000 individuals - to determine any association between a genetic predisposition to abdominal adiposity and cardiometabolic disease and its risk factors. The results clearly indicated that genetic predisposition to abdominal adiposity is associated with significant increases in the incidence of type 2 diabetes and coronary heart disease, along with increases in blood lipids, blood glucose and systolic blood pressure. No association was found between the genetic risk score and lifestyle factors, and testing confirmed that only the abdominal adiposity effects of the identified gene variants were associated with cardiometabolic risk. "These results illustrate the power of using genetics as a method of determining the effects of a characteristic like abdominal adiposity on cardiometabolic outcomes," says lead author Connor Emdin, DPhil, of the MGH Center for Genomic Medicine and the Cardiology Division. "The lack of association between the body type genetic risk score and confounding factors such as diet and smoking provides strong evidence that abdominal adiposity itself contributes to causing type 2 diabetes and heart disease." Emdin continues, "Not only do these results allow us to use body shape as a marker for increased cardiometabolic risk, they also suggest that developing drugs that modify fat distribution may help prevent these diseases. Future research also could identify individual genes that could be targeted to improve body fat distribution to reduce these risks." Additional co-authors of the JAMA paper are Amit Khera, MD, Pradeep Natarajan, MD, Derek Klarin, MD, and Seyedeh Zekavat, all of the MGH Center for Genomic Medicine; and Allan Hsiao, MPhil, Massachusetts Institute of Technology. Support for the study includes National Institutes of Health grants R01 HL127564, and T32 HL0007734; the Ofer and Shelly Nemirovsky MGH Research Scholar Award; and grants from the Rhodes Trust, and the Donovan Family Foundation. Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $800 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2016 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."
News Article | December 21, 2016
Crafting a vaccine against RSV (respiratory syncytial virus) has been a minefield for 50 years, but scientists believe they have found the right balance. Researchers at Emory University School of Medicine and Children's Healthcare of Atlanta report that they have engineered a version of RSV that is highly attenuated - weakened in its ability to cause disease - yet potent in its ability to induce protective antibodies. The researchers examined the engineered virus using cryo-electron microscopy and cryo-electron tomography techniques, and showed that it is structurally very similar to wild type virus. When used as a vaccine, it can protect mice and cotton rats from RSV infection. The results are scheduled for publication in Nature Communications on December 21. "Our paper shows that it's possible to attenuate RSV without losing any immunogenicity," says senior author Martin Moore, PhD, associate professor of pediatrics at Emory University School of Medicine and a Children's Healthcare of Atlanta Research Scholar. "This is a promising live-attenuated vaccine candidate that merits further investigation clinically." The next steps for this vaccine are to produce a clinical grade lot and conduct a phase 1 study of safety and immunogenicity in infants, Moore says. RSV is the number one cause of pneumonia deaths in children worldwide and one of the top causes of infant hospitalization in the United States. Most children in the USA become infected in the first year of life. Even so, there is no vaccine against RSV available. In the 1960s, an attempt to develop an RSV vaccine by chemically inactivating the virus, like in a standard flu shot, backfired. Exposure to this vaccine actually made natural RSV infection in infants worse. More recently, a clinical trial of a protein-only RSV vaccine in older adults showed disappointing results. Several successful vaccines against other viruses, likes measles, polio, and mumps, have been created by weakening the viruses in cell culture. A strain that is safe enough for use as a vaccine, but still stimulates the immune system, is supposed to result. "Achieving that balance is a challenge," Moore says. "Weakening RSV by passage hasn't worked out satisfactorily. It turns out that for RSV, the natural virus does not induce a lot of immunity itself." Instead, Moore and his colleagues engineered RSV to enhance production of a key protein, called F (for fusion). F is critical for RSV's ability to enter cells and is the target of several vaccines in development. By making mutations in the viral gene that encodes F, the researchers also made the virus more stable with respect to heat, which could help vaccine manufacturing and distribution. At the same time, the researchers removed or weakened several other viral genes that promote infection and suppress the immune system. One measure of this is that the modified virus, called OE4, stimulates high levels of antibody production. Moore and his team rewrote several of the viral genes in the OE4 strain using a process called codon-deoptimization, which makes it less likely for a re-engineered virus to mutate back to its original form. When examined via cryo-electron microscopy and cryo-electron tomography, OE4 virions were structurally very similar to standard RSV virions. The researchers used techniques that allow the virions to be preserved in their native states, says co-senior author Elizabeth R. Wright, PhD, associate professor of pediatrics at the Emory University School of Medicine. Wright is director of the Robert P. Apkarian Integrated Electron Microscopy Core and a Georgia Research Alliance Distinguished Investigator. Immuno-EM experiments revealed that OE4 had higher levels of the pre-fusion, form of the F protein and lower levels of the attachment protein called G. In addition, a Georgia Tech graduate student in Wright's lab, Zunlong Ke, analyzed cryo-ET data and found that that the majority of F proteins on both viruses preserved immediately after budding was in the pre-fusion conformation. This is the structural evidence that the vaccine candidate (OE4) is highly immunogenic though highly attenuated, Wright says. OE4 vaccination could completely protect mice and cotton rats against later infection by standard forms of RSV. In contrast with a chemically inactivated RSV vaccine, OE4 did not result in enhanced lung disease in cotton rats. Christopher Stobart, PhD, now assistant professor of biology at Butler University, and instructor Christina Rostad, PhD are co-first authors of the paper. Cotton rat studies were performed at Baylor College of Medicine and at Sigmovir Biosystems. Emory has optioned the vaccine technology to a startup company, Meissa Vaccines, Inc. Moore co-founded and serves as chief scientific officer for Meissa Vaccines, Inc. Moore, Stobart, Rostad, and co-authors Anne Hotard and Jia Meng are co-inventors in a patent application describing the RSV vaccine reported in the Nature Communications paper. Emory and Moore could benefit financially from this technology, and this relationship has been reviewed and approved by Emory University School of Medicine. The research was supported by the National Institute of Allergy and Infectious Diseases (R01AI087798, U19AI095227, T32AI074492), the Atlanta Pediatric Scholars program (K12HD072245) and a pilot grant from the Emory/Children's/Georgia Tech Center for Childhood Infections and Vaccines.
News Article | November 12, 2016
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Leap Therapeutics, Inc. today announced the presentation of data from its Phase 1 clinical trial of TRX518 in patients with advanced relapsed or refractory solid tumors. Roberta Zappasodi, Ph.D., Parker Institute Scholar and Research Scholar in the Ludwig Collaborative Laboratory at Memorial Sloan Kettering Cancer Center, a site participating in the Phase 1 study, led an oral presentation during the Presidential Session entitled “Analysis of pharmacodynamic bi
News Article | October 31, 2016
Nearly 7 in 10 cigarette smokers are looking for a way to quit - and many smokers have turned to e-cigarettes for help. A researcher at the Oklahoma Tobacco Research Center at the Stephenson Cancer Center has received a 5-year, $3 million R01 grant from the National Cancer Institute to study the impact of e-cigarette usage on smoking rates. The grant was awarded to Theodore Wagener, PhD, assistant professor of pediatrics, associate director for training at the Oklahoma Tobacco Research Center, and an Oklahoma TSET Research Scholar. National Cancer Institute R01 grants are the oldest and most prestigious type of cancer research grants. Wagener's research will assess how effective different types of e-cigarettes are in helping smokers switch from cigarettes to these vaping products and what impact switching has on smokers' exposure to harmful carcinogens and cancer risk. "We know that traditional combustible cigarettes, when used as intended kill one out of three smokers and is the leading cause of preventable death," Wagener said. "There may be a potential benefit if smokers switch to e-cigarettes completely, but we need additional research to understand to what extent." Since e-cigarettes have emerged on the market, the design and nicotine delivery has evolved. The newest generation of high-powered e-cigarettes is able to deliver nicotine much more like a cigarette, but with much lower levels of cancer-causing agents and no carbon monoxide. Early research demonstrates that an e-cigarette user may see some health benefit if they switch completely to the newer generation of e-cigarettes and reduce their exposure to combustible cigarette smoke. "Missing from the current literature is a long-term randomized trial assessing differences between earlier, low-powered e-cigarette devices and newer, high-powered devices on affecting smoking behaviors, nicotine addiction, and users' exposure to harmful chemicals and the resulting changes in cancer risk," said Wagener. Wagener's study will monitor levels of chemicals and toxicants in an e-cigarette user's body and inform the developing research base about the health impacts of e-cigarettes. Through this improved understanding, the study hopes to better inform the Food and Drug Administration as it considers any product-specific regulations. Historically, the e-cigarette market has been unregulated. As a TSET Research Scholar, Wagener, a clinical psychologist, has used a grant from TSET to fund research into the evolving field of e-cigarette use for more than four years. These pilot studies allowed Wagener to gather the necessary data to apply for the National Cancer Institute grant. "[E-cigarettes are] a new and evolving field for tobacco addiction, and it's important that those working to end tobacco use, regulators and consumers have the best information needed to make informed decisions," said TSET Executive Director Tracey Strader. "While the science on e-cigarettes is developing, wedo know that nicotine is not good for the developing brains of youth and young adults, and that children, pregnant women, and nonsmokers should not be exposed to the secondhand aerosol from e-cigarettes. Dr. Wagener's research will certainly benefit Oklahomans, and should have relevance for the nation, and across the globe." According to the Centers for Disease Control and Prevention, cigarette smoking is responsible for more than 480,000 deaths each year in the United States alone. The e-cigarette research is funded by NCI grant R01 CA204891.
News Article | December 24, 2016
The 12th International conference of the World Association for Vedic Studies was successfully held from the 15th to 18th of December at the Bharatiya Vidya Bhavan, New Delhi. The main theme of the conference was Scientific aspects of Vedic knowledge and it was held jointly with the 20th Conference of Wider Association of Vedic Studies of India. On the inaugural day Dr. Shashi Tiwari, General Chair of the conference, pointed out that while one cannot expect the Vedas to be used as modern science textbooks, the scientific knowledge of the Vedas must still be appreciated. The conference co-chair was Dr. R.P. Singh of JNU, who helped with the editing of the 130 peer-reviewed papers and invited talks. In addition to focusing on the main theme of the conference, scholars also analysed the use of Vedic concepts for world peace, ecology, human rights, and solutions to the crises faced by modern civilization. Ashok Pradhan, Director of the Delhi Kendra of Bharatiya Vidya Bhavan (BVB), pointed to the relevance of the conference to BVB’s mission, and was optimistic that the conference would remove many misconceptions and encourage intellectuals to explore the scientific aspects of the Vedas. Professor Ram Karan Sharma, President of WAVES India, and Sashi Kejriwal, President of WAVES International, placed emphasis on the fact that this 12th WAVES conference was appropriately being held at the geographical center of the Vedic civilization. Sashi Kejriwal felt that it was “mission accomplished. After eleven conferences in the Americas, the first conference in India has brought about a positive resonance amongst the scholars of Vedic studies in India, especially amongst the younger ones.” Dhirendra Shah, Director and treasurer of the Board of WAVES International, remarked on the contributions of the WAVES as a multidisciplinary academic organization since its foundation in 1996, in promoting ancient Indian traditions and Vedic wisdom through its conferences and other activities. Published contributions have advanced knowledge on the Sarasvati civilization, Ayurveda, science and mathematics, and other topics. Promoting awareness of the contributions from the Indian Civilization in all these fields is critical in inspiring young Indians. Other messages on the relevance of the conference came from Dr. Lallan Prasad, VP of WAVES India, Dr. Bhudev Sharma, Founder and Past President of WAVES International, Dr. Balram Singh, Founder of the Maryada Foundation, and Rajiv Malhotra, founder of the Infinity Foundation and renowned author on Indology and its modern challenges. Dr. S. Kalyanaraman of the Saraswati Foundation welcomed the conference with his message of significant new discoveries linking 2500 BCE metalwork to the inscriptions found at Binjor in the heart of the Saraswati River Civilization. The conference consisted of keynote speeches, plenary lectures, panel discussions, and academic sessions for presentation of research papers, and attracted nearly 200 scholars from four different continents. The discussion focused on abstract concepts of quantum mechanics and consciousness to more practical and contextual issues like the caste system and health. One of the major features of this year’s biennial conference was the participation of a large number of young scholars, especially from India. Dr. Ved Mitra Shukla of Delhi University felt it was a very positive development for his and other students. “Students got an opportunity to get a flavour of international relevance of their work,” said Shukla. Dr. Shakuntala, a faculty member from a college in Assam, who led a group of research students at the conference said, “We need more such international conferences in India to expose our students and scholars to the latest advances in knowledge happening at a fast pace.” Various scholarly presentations touched on the knowledge present in the Vedas in the areas of metallurgy, nanosciences, holistic health, gynaecological techniques, environmental sustainability, social stability, chronology of major events, concepts of economic equality and human rights, etc. Dr. John Kinneman of University of Colorado discussed consciousness in cell biology that could form the basis of new approach to modern sciences. Dr. Indrani Rampersad of Trinidad proposed that epics like Ramayana help in the preservation of the civilizational culture and values that date back many millennia. Dr. Robert Schneider of Maharishi University of Managament, Iowa, US, presented a paper on the subtle power of the mind and the use of consciousness that can give us the power to keep from aging. This power has practical value in healthcare. Dr. Koenraad Elst from Belgium narrated a provocative theory that certain yoga practices, such as kundalini, may have their origin in China. The valedictory session was presided over by the WAVES India Vice President Dr. Lallan Prasad. It included key speeches by Dr. Bhudev Sharma, founder of WAVES, Dr. Bhakti Nishkam Shanta of Sri Chaitanya Institute of Bengaluru, Dr. Narayanan Komerath of Georgia Tech, Dr. Narahari Achar of University of Memphis, Paul Palmorozza of St. James School, London, Dr. Bal Ram Singh, and Sashi Kejriwal and Dhirendra Shah, President and treasurer, respectively, of WAVES International. Speakers emphasized the involvement of young scholars and students in Vedic studies to make these relevant to modern times and for solving the various problems modern day society faces. The reaction from the delegates was very positive. “It raised my interest in Indology, especially towards Vedas and Epics,” said Jayati Saxena, a Philosophy Research Scholar at Delhi University. Dr. Narahari Achar said, “I am impressed by the range and depth of the topics presented…. and by the participation from young scholars.” This sentiment was echoed by Pooja Vashistha, a Master’s student in the Sanskrit Department at Delhi University. “I found it [conference] really knowledgeable and very interesting….I felt very lucky.” Dr. Bal Ram Singh, who is also the Founding Director of the Center for Indic Studies at the University of Massachusetts and currently the Executive Mentor of the School of Indic Studies at the Institute of Advanced Sciences, implored scholars to make Vedic knowledge useful to the current society. Karthik Amaanchi of Srimaharshi Research Institute of Vedic Technology, Guntur, Andhra Pradesh, presented a paper on how ancient knowledge is used by his Institute to develop nanomaterials. Deeper study is needed to bring out various secrets locked in the Vedas, according to Dr. Bhakti Nishkam Shanta. “Let us encourage the inquiry of the self, origin of both matter and life through education and research.” An impressive presentation was made by Mr. Tahashin Mandal of Aligarh Muslim University on the Vedic wisdom related to the development of the foetus in the mother’s womb, an area still lacking some understanding in modern science. Dr. Narayanan Komerath, highlighted his journey in writing his recent book, “Writing an Introductory Textbook on Sanatana Dharma for a Global Audience”, was impressed by the passion of presenters in languages other than English. "Several papers and presentations discussed in Hindi and Sanskrit by senior scholars and Masters/Doctoral candidates, brought special insights into the richness of the scholarly discourse on Vedic studies". The invaluable help provided by Bharaitiya Vidya Bhavan, and by the local team of volunteers headed by Dr. Shashi Tiwari and Dr. Aparna Dhir, was acknowledge by all that attended the four day conference.
News Article | March 28, 2016
Certain types of bacteria in the gut can leverage the immune system to decrease the severity of stroke, according to new research from Weill Cornell Medicine. This finding can help mitigate stroke -- which is the second leading cause of death worldwide. In the study, published March 28 in Nature Medicine, mice received a combination of antibiotics. Two weeks later, the researcher team -- which included collaborators at Memorial Sloan Kettering Cancer Center -- induced the most common type of stroke, called ischemic stroke, in which an obstructed blood vessel prevents blood from reaching the brain. Mice treated with antibiotics experienced a stroke that was about 60 percent smaller than rodents that did not receive the medication. The microbial environment in the gut directed the immune cells there to protect the brain, the investigators said, shielding it from the stroke's full force. "Our experiment shows a new relationship between the brain and the intestine," said Dr. Josef Anrather, the Finbar and Marianne Kenny Research Scholar in Neurology and an associate professor of neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine. "The intestinal microbiota shape stroke outcome, which will impact how the medical community views stroke and defines stroke risk." The findings suggest that modifying the microbiotic makeup of the gut can become an innovative method to prevent stroke. This could be especially useful to high-risk patients, like those undergoing cardiac surgery or those who have multiple obstructed blood vessels in the brain. Further investigation is needed to understand exactly which bacterial components elicited their protective message. However, the researchers do know that the bacteria did not interact with the brain chemically, but rather influenced neural survival by modifying the behavior of immune cells. Immune cells from the gut made their way to the outer coverings of the brain, called the meninges, where they organized and directed a response to the stroke. "One of the most surprising findings was that the immune system made strokes smaller by orchestrating the response from outside the brain, like a conductor who doesn't play an instrument himself but instructs the others, which ultimately creates music," said Dr. Costantino Iadecola, director of the Feil Family Brain and Mind Research Institute and the Anne Parrish Titzell Professor of Neurology at Weill Cornell Medicine. The newfound connection between the gut and the brain holds promising implications for preventing stroke in the future, which the investigators say might be achieved by changing dietary habits in patients or "at risk" individuals. "Dietary intervention is much easier to accomplish than drug use, and it could reach a broad base," Dr. Anrather said. "This is a little far off from the current study -- it's music of the future. But diet has the biggest effect of composition of microbiota, and once beneficial and deleterious species are identified, we can address them with dietary intervention."