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News Article | May 10, 2017
Site: www.eurekalert.org

Among today's most promising weapons against cancer is the use of therapies that direct the immune system against a tumor. One approach - immune checkpoint blockade - is designed to circumvent the "off switches" that prevent the immune system from attacking healthy tissues but also can shield a tumor from the immune response. These drugs have had remarkable success in some but not all patients, and long-term survival has been achieved in a minority of patients. Now a study from Massachusetts General Hospital (MGH) investigators has identified a surprising mechanism for resistance to immune checkpoint blockade. In their paper published online in Science Translational Medicine, the researchers describe finding that an antibody-based drug designed to block the immunosuppressive molecule PD-1 is removed from its target T cells by macrophages within minutes of administration in several mouse models of cancer. They also identify the molecular mechanism behind this drug capture, which could lead to ways to prevent the process. "Immune checkpoint blockers are very effective in some patients but not others, and our current ability to understand why treatments work or fail is quite limited," says Mikael Pittet, PhD, director of the Cancer Immunology Program in the MGH Center for Systems Biology and senior author of the report. "Using high-resolution molecular imaging to track immune checkpoint drugs in real time, we were able to discover what was happening, devise ways to extend the time the drug binds to its target and improve treatment efficacy in our models." Immune checkpoint molecules like PD-1 are expressed on the surface of CD8 T cells - the immune system's "killer cells" that attack cells that are damaged or diseased, including cancer cells - and act to suppress an inappropriate T cell response. Monoclonal antibodies that block pathways controlled by checkpoint molecules are the basis of current checkpoint blockade drugs. The MGH team used intravital microscopy - which examines biological processes in living animals through tiny implanted windows - to track the activity of an antiPD-1 drug in mouse models of colon cancer. As expected, the labeled antibody was observed to bind to PD-1 molecules on CD8 T cells within a few minutes. But as little as 20 minutes later, the drug had been taken up by macrophages within the tumors. The same process of rapid antibody binding to PD-1 molecules on CD8 T cells, followed by macrophage uptake, was observed in models of melanoma and lung cancer. To determine how the antibodies were being removed from T cells, the researchers first confirmed that the macrophages neither expressed PD-1 molecules nor did they take up antibody not bound to T cells. Experiments in mouse and human tumor cells revealed that antibody removal was accomplished through the interaction of the Fc region - the portion of an antibody that communicates with and directs the action of immune cells - and Fc receptors on the surface of macrophages. Administering an Fc receptor inhibitor prior to anti-PD-1 treatment both extended the binding of the drug to CD8 T cells and led to complete tumor disappearance in a mouse model. Whether a similar strategy could improve the results of immune checkpoint blockade in human patients may be answered by current clinical trials that combine immune checkpoint blockers with drugs targeting macrophages, which have number of detrimental effects in cancer. "Our observations would not have been possible without a method of dynamically imaging drug action on a cellular level," says Pittet, who is an associate professor of Radiology at Harvard Medical School. "Our platform for imaging anti-PD-1 in live animals can easily be adapted to study additional checkpoint blockade agents, so we are building a program to track the cellular interactions that will allow us to decipher drug mechanisms and hopefully leverage knowledge into engineering better therapeutics." The lead authors of the Science Translational Medicine report are Sean Arlauckas, PhD, and Christopher S. Garris, MGH Center for Systems Biology. Additional co-authors are Rainer Kohler, PhD, Michael Cuccarese, PhD, Katherine Yang, PhD, Miles Miller, PhD, Jonathan Carlson, MD, PhD, and Ralph Weissleder, MD, PhD, Center for Systems Biology; Maya Kitaoka and Robert Anthony, PhD, MGH Center for Immunology and Infectious Disease; and Gordon Freeman, PhD, Dana-Farber Cancer Institute. Support for the study includes the Samana Cay MGH Research Scholar Fund, National Institutes of Health grants R01AI084880, R01CA164448, R21CA190344, U54-CA151884, P50CA086355, DP2AR068272-01, and HL084312; Department of Defense grant PC140318, and the David H. Koch-Prostate Cancer Foundation Award in Nanotherapeutics. 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, genomic medicine, 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 | May 15, 2017
Site: www.eurekalert.org

BOSTON- As of this year, kids under the age of 15 only need 2 doses of HPV vaccine. New research out of Boston Medical Center, published online in the STD Journal, is the first published clinical evidence to support new recommendations by the Center for Disease Control and Prevention (CDC) for a two-dose HPV vaccine to prevent genital warts. BMC researchers found that the two-dose human papillomavirus (HPV) vaccine provides the same level of protection against genital warts as three doses, when given as directed. The study looked at nearly 400,000 girls from around the country to find the rate of genital warts based on the number of vaccine doses received. Researchers found that receiving two or three doses of the vaccine was effective. Both provided significantly more protection against genital warts than one dose or not receiving the vaccine at all. The vaccine is recommended to prevent HPV infections and its associated diseases, including cancers and genital warts. Recently, the CDC and the World Health Organization (WHO) updated their recommendations from a three to two dose vaccine schedule for girls and boys ages 9 to 14. "The CDC and WHO based the new two dose schedule primarily on immunogenicity results, but there was very little research on how effective that recommendation has been," said Rebecca Perkins, MD, obstetrician at BMC and the study's lead author. "This study validates the new recommendations and allows us to confidently move forward with the 2 dose schedule for the prevention of genital warts." Researchers did note that the rate of genital warts for all girls dropped significantly from 2007 to 2013 and attribute the trend to the wide distribution of the HPV vaccine in recent years. "The data supporting a two dose schedule is encouraging, but it only reports on genital warts, not cervical dysplasia or cancer outcomes. Collecting that long term data is paramount," said Perkins, who is also an associate professor of obstetrics and gynecology at Boston University School of Medicine. "This study will be a stepping stone for future research into the effectiveness of the two dose schedule of the HPV vaccine for other symptoms of the disease." The study was funded by the American Cancer Society Mentored Research Scholar Grant (MRSG-09-151-01). Boston Medical Center is a private, not-for-profit, 493-bed, academic medical center that is the primary teaching affiliate of Boston University School of Medicine. It is the largest and busiest provider of trauma and emergency services in New England. Committed to providing high-quality health care to all, the hospital offers a full spectrum of pediatric and adult care services including primary and family medicine and advanced specialty care with an emphasis on community-based care. Boston Medical Center offers specialized care for complex health problems and is a leading research institution, receiving more than $119 million in sponsored research funding in fiscal year 2015. It is the 11th largest recipient of funding in the U.S. from the National Institutes of Health among independent hospitals. In 1997, BMC founded Boston Medical Center Health Plan, Inc., now one of the top ranked Medicaid MCOs in the country, as a non-profit managed care organization. It does business in Massachusetts as BMC HealthNet Plan and as Well Sense Health Plan in New Hampshire, serving more than 315,000 people, collectively. Boston Medical Center and Boston University School of Medicine are partners in the Boston HealthNet - 14 community health centers focused on providing exceptional health care to residents of Boston. For more information, please visit.


News Article | April 20, 2017
Site: www.cemag.us

With the depletion of nonrenewable energy sources and the increase of pollution, researchers have turned to finding ways to harness clean energy from cheap alternative sources. Researchers at The University of Toledo have recently focused their investigation in the area of perovskite solar cell technology. Perovskite is a compound material with a special crystal structure, according to Dr. Yanfa Yan, Ohio Research Scholar chair and UT professor of physics. “Metal halide perovskites can effectively harvest sunlight and efficiently convert it into usable electrical power. They have the potential to be used for fabricating cheap and highly efficient solar cells,” he says. “Perovskite photovoltaic technology has attracted tremendous interest in the past several years.” Current conventional solar cells are made out of materials such as silicon, a material more expensive than perovskite solar cells. Yan explains that his research combined theoretical and experimental approaches to understand the fundamental mechanisms of the limitations of the perovskites and to develop processes and design new materials to overcome the limitations. “Our ultimate goal is to help improve the energy conversion efficiencies of photovoltaic cells and solar fuel devices,” Yan says. He and his team did just that. In fact, their research revealed a world record efficiency for the conversation of sunlight to electricity in the area of perovskite solar cell technology using less toxic lead as well as demonstrated a concept for producing an all-perovskite tandem solar cell that can bring together two different solar cells to increase the total electrical power generated by using two different parts of the sun’s spectrum. “We reported a method that can easily be followed by other researchers in the field,” Yan says. The research has been published in the journal Nature Energy. “The publication of this paper in Nature Energy shows a significant recognition of our work by the peers in the field of photovoltaics,” Yan says. “We are very proud of our achievements.” He adds, “We are thankful for collaborations with colleagues in the Wright Center for Photovoltaics Innovational and Commercialization at UT.” “Dr. Yan and his team are doing outstanding work on this promising type of solar cell, paving the way for cheaper and more efficient ways to provide clean renewable energy to meet the needs of society,” says Dr. Karen Bjorkman, dean of the College of Natural Sciences and Mathematics; Distinguished University Professor of Astronomy; and Helen Luedtke Brooks Endowed Professor of Astronomy. “The faculty and researchers in the Department of Physics and Astronomy and UT’s Wright Center for Photovoltaic Innovation and Commercialization continue to lead the way in improving photovoltaic devices to address our growing energy demands through sustainable and renewable means.”


News Article | May 1, 2017
Site: www.eurekalert.org

IMAGE:  Ovarian cancer tumors with higher percentages of cIAP-expressing cells, shown in red at left, were more sensitive to a potential combination therapy than tumor cells without cIAP-expressing cells. view more Researchers have been trying to understand why up to 85 percent of women experience recurrence of high-grade serous ovarian cancer -- the most common subtype of ovarian cancer -- after standard treatment with the chemotherapy drug carboplatin. Preclinical research from Dr. Sanaz Memarzadeh, who is a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, has potentially solved this mystery and pinpointed a combination therapy that may be effective for up to 50 percent of women with ovarian cancer. Memarzadeh's research, published in the journal Precision Oncology, shows a new combination therapy of carboplatin and an experimental drug called birinapant can improve survival in mice with ovarian cancer tumors. Additional findings reveal that testing for a specific protein could identify ovarian tumors for which the treatment could be effective. Importantly, the treatment could also target cancers that affect other parts of the body, including the bladder, cervix, colon and lung cancer. In 2015, Memarzadeh and her team uncovered and isolated carboplatin-resistant ovarian cancer stem cells. These cells have high levels of proteins called cIAPs, which prevent cell death after chemotherapy. Since the cancer stem cells survive carboplatin treatment, they regenerate the tumor; with each recurrence of ovarian cancer, treatment options become more limited. Memarzadeh showed that birinapant, which degrades cIAPs, can make carboplatin more effective against some ovarian cancer tumors. "I've been treating women with ovarian cancer for about two decades and have seen firsthand that ovarian cancer treatment options are not always as effective as they should be," said Memarzadeh, director of the G.O. Discovery Lab and member of the UCLA Jonsson Comprehensive Cancer Center. "Our previous research was promising, but we still had questions about what percentage of tumors could be targeted with the birinapant and carboplatin combination therapy, and whether this combination could improve overall survival by eradicating chemotherapy-resistant ovarian cancer tumors." In this new study, the research team first tested whether the combination therapy could improve survival in mice. Half of the mice tested had carboplatin-resistant human ovarian cancer tumors and the other half had carboplatin-sensitive tumors. The team administered birinapant or carboplatin as well as the two drugs combined and then monitored the mice over time. While birinapant or carboplatin alone had minimal effect, the combination therapy doubled overall survival in half of the mice regardless of whether they had carboplatin-resistant or carboplatin-sensitive tumors. "Our results suggest that the treatment is applicable in some, but not all, tumors," said Rachel Fujikawa, a fourth year undergraduate student in Memarzadeh's lab and co-first author of the study. To assess the combination therapy's rate of effectiveness in tumors, the team went on to test 23 high-grade serous ovarian cancer tumors from independent patients. Some were from patients who had never been treated with carboplatin and some were from patients who had carboplatin-resistant cancer. With these samples, the researchers generated ovarian cancer tumors utilizing a method called disease-in-a-dish modeling and tested the same treatments previously tested in mice. Once again, carboplatin or birinapant alone had some effect, while the combination of birinapant and carboplatin successfully eliminated the ovarian cancer tumors in approximately 50 percent of samples. Importantly, the combination therapy worked for both carboplatin-resistant and carboplatin-sensitive tumors. The researchers also measured cIAPs (the target for the drug birinapant) in the tumors. They found a strong correlation between cancer stem cells with high levels of cIAP and a positive response to the combination therapy. Since elevated levels of cIAPs have been linked to chemotherapy resistance in other cancers, the researchers wondered if the combination therapy could effectively target those cancers as well. The team created disease-in-a-dish models using human bladder, cervix, colon and lung cancer cells and tested the combination therapy. Similar to the ovarian cancer findings, 50 percent of the tumors were effectively targeted and high cIAP levels correlated with a positive response to the combination therapy. "I believe that our research potentially points to a new treatment option. In the near future, I hope to initiate a phase 1/2 clinical trial for women with ovarian cancer tumors predicted to benefit from this combination therapy," said Memarzadeh, gynecologic oncology surgeon and professor at the David Geffen School of Medicine at UCLA. The research was supported by an American Cancer Society Research Scholar Grant (RSG-14-217-407 01-TBG), the Phase One Foundation, the Ovarian Cancer Circle Inspired by Robin Babbini, a STOP Cancer Margot Lansing Memorial Seed award, the National Institutes of Health (R01CA183877 and #U54 MD007598) and the UCLA Broad Stem Cell Research Center.


News Article | April 28, 2017
Site: www.businesswire.com

NEW YORK--(BUSINESS WIRE)--Weill Cornell Medicine today announced a gift made by WorldQuant, LLC (“WorldQuant”) and Igor Tulchinsky that will further realize the promise of precision medicine. The $5 million gift establishes a new initiative that will use predictive tools to enhance Weill Cornell Medicine’s capability to diagnose and treat a variety of illnesses, with the goal of improving outcomes for patients. The WorldQuant Initiative for Quantitative Prediction brings together financial and medical experts whose collaboration strives to enhance biomedical research. Weill Cornell Medicine’s scientists, working closely with researchers and technologists from WorldQuant, will deploy predictive tools and quantitative methods to deepen the understanding of genetic factors that drive disease in individual patients. Using sophisticated algorithms, the new initiative will enable the research team to analyze genomic data to identify patterns and trends that may predict patients’ future risk of developing disease, as well as potential outcomes. These insights may be used to improve the diagnosis and treatment of a variety of illnesses, including cancer, neurological disorders, cardiovascular diseases and infections. Weill Cornell Medicine researchers Dr. Christopher Mason, the WorldQuant Research Scholar, and Dr. Olivier Elemento, the Walter B. Wriston Research Scholar, will lead the initiative, which will involve joint work with physician-scientists at the Caryl and Israel Englander Institute for Precision Medicine and the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “This outstanding gift will accelerate and expand Weill Cornell Medicine’s approach to precision medicine, providing new predictive tools that will lead to even better outcomes for patients,” said Jessica Bibliowicz, chairman of the Weill Cornell Medicine Board of Overseers. “We are very grateful to Igor Tulchinsky and WorldQuant, LLC for making this initiative possible.” “The use of quantitative prediction for patients represents an important new tool at Weill Cornell Medicine,” said Dr. Augustine M.K. Choi, the Stephen and Suzanne Weiss Dean at Weill Cornell Medicine. “We appreciate Mr. Tulchinsky’s generosity, which will help us achieve new goals in the rapidly evolving field of precision medicine.” For WorldQuant, an international quantitative investment management firm founded by Mr. Tulchinsky, who is chairman and CEO, applying predictive algorithms to medical research is a natural progression. “There is a great opportunity to leverage the technology and proprietary algorithms we’ve developed for use outside of the financial markets, particularly around predictive medicine and cancer research, where the stakes are so high,” said Mr. Tulchinsky, a member of the Board of Overseers at Weill Cornell Medicine. “This initiative has tremendous possibilities, and I am proud to help drive advances in the field.” Drs. Mason and Elemento, as co-directors of the initiative, will leverage new technologies to analyze clinical samples and visualize various diseased tissues at single-cell resolution. These methods will be combined with a supercomputing infrastructure, which includes developing new software to crunch data using advanced pattern-recognition algorithms to model disease progression. One of the initiative’s ultimate goals is to give researchers the ability to examine a blood draw or urine sample from one patient and predict his or her future risk for developing a specific type of cancer. The same technology could also give researchers the ability to rapidly diagnose patients and predict which treatments might work, which treatments may encounter resistance and how the disease is likely to progress. In the future, this framework may enable investigators to analyze single cells and molecules from blood, tumor biopsies, saliva or other clinical samples collected from patients seeking care at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, and then use analytical algorithms to create personalized predictive models based on findings from longitudinal healthcare data collected from thousands of patients. To accomplish this, Drs. Mason and Elemento will work closely with WorldQuant’s research team and intend to recruit software engineers and experts in artificial intelligence who can develop innovative quantitative prediction tools and analyze findings. They will continue to provide advanced training in quantitative biology and modeling to Weill Cornell Medicine’s physician-scientists to support this effort. “We are looking forward to using the tools and methods that will result from this philanthropic investment to tease apart disease cells’ secrets and create predictive models of health for patients,” said Dr. Mason, who is also an associate professor of physiology and biophysics, an associate professor of computational genomics at the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine, and an associate professor of neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine. “Not only does this gift enable new science and predictive models in medicine, it also creates an unprecedented collaboration between two big-data groups at Weill Cornell Medicine and WorldQuant.” “This incredibly generous gift will likely spur a whole new generation of biomedical discoveries by helping bring predictive disease analytics to precision medicine,” said Dr. Elemento, who is also associate director of the Institute for Computational Biomedicine and an associate professor of physiology and biophysics at Weill Cornell Medicine. “We’re profoundly thankful to Igor for his support, and grateful to have WorldQuant as a partner in pioneering new approaches to understanding cancer, infections and neurological diseases.” Weill Cornell Medicine is committed to excellence in patient care, scientific discovery and the education of future physicians in New York City and around the world. The doctors and scientists of Weill Cornell Medicine — faculty from Weill Cornell Medical College, Weill Cornell Graduate School of Medical Sciences, and Weill Cornell Physician Organization — are engaged in world-class clinical care and cutting-edge research that connect patients to the latest treatment innovations and prevention strategies. Located in the heart of the Upper East Side's scientific corridor, Weill Cornell Medicine's powerful network of collaborators extends to its parent university Cornell University; to Qatar, where an international campus offers a U.S. medical degree; and to programs in Tanzania, Haiti, Brazil, Austria and Turkey. Weill Cornell Medicine faculty provide comprehensive patient care at NewYork-Presbyterian Weill Cornell Medical Center, NewYork-Presbyterian Lower Manhattan Hospital and NewYork-Presbyterian Queens. Weill Cornell Medicine is also affiliated with Houston Methodist. For more information, visit weill.cornell.edu. WorldQuant, LLC is a global quantitative investment firm that was founded in 2007 by Igor Tulchinsky and now has more than $5 billion in assets under management. The firm has more than 20 offices in 15 countries and over 600 employees and 500 consultants. WorldQuant develops and deploys systematic investment strategies across a variety of asset classes in global markets, utilizing a proprietary research platform and investment process. For more information on WorldQuant’s culture and philosophy, please visit www.WeAreWorldQuant.com.


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

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."


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
Site: www.eurekalert.org

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 | November 12, 2016
Site: www.businesswire.com

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
Site: www.eurekalert.org

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.

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