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| 3482 | NCATS Announces CTSA Program Hub Awards to Help Transform How Clinical and Translational Science Is Conducted Nationwide | Turning scientific discoveries into clinical advances often takes too long. To help address challenges and get more treatments to more patients more quickly, NCATS has announced new funding for 18 Clinical and Translational Science Awards (CTSA) Program hubs. The CTSA Program comprises an innovative national network of medical research institutions — called hubs — that work together to improve the translational research process. The hubs collaborate locally, regionally and nationally, catalyzing innovation in human subjects research, patient involvement, new translational methodologies and training. “The CTSA Program is tackling system-wide scientific and operational problems to make the clinical and translational research enterprise more efficient,” said NCATS Director Christopher P. Austin, M.D. Hub awardees include the State University of New York at Buffalo and Wake Forest University Health Sciences, both of which are new CTSA Program hubs. The full list of awarded institutions is: Boston University Georgetown-Howard Universities, Washington, D.C. Medical College of Wisconsin, Milwaukee Medical University of South Carolina, Charleston Mount Sinai School of Medicine, New York City New York University Langone Medical Center, New York City Northwestern University, Chicago State University of New York at Buffalo University of Alabama at Birmingham University of California, Irvine University of California, San Diego University of Cincinnati University of Florida, Gainesville University of Iowa, Iowa City University of Massachusetts Medical School, Worcester University of New Mexico Health Sciences Center, Albuquerque University of Texas Medical Branch at Galveston Wake Forest University Health Sciences, Winston-Salem, North Carolina “These institutions will collaborate with each other and with additional CTSA Program hubs in our network to develop, demonstrate and disseminate innovative methods and technologies to turn scientific discoveries into clinical advances,” said Petra Kaufmann, M.D., M.Sc., director of NCATS’ Division of Clinical Innovation and Office of Rare Diseases Research. View descriptions of these awardees and other CTSA Program hubs. To learn more about how investigators supported through the CTSA Program are translating basic discoveries into improved health, visit the CTSA Program page. Posted October 2015 | ||||||||
| 3483 | Wake Forest Clinical & Translational Science Institute | Principal Investigator King Li, M.D., M.B.A., Wake Forest Baptist Medical Center Website The Wake Forest Clinical & Translational Science Institute (CTSI) provides an innovative, efficient and sustainable infrastructure to accelerate Wake Forest’s transformation into a learning health care system and thus speed the translation of discoveries to improve health. CTSI will: Develop a competent, diverse translational workforce prepared to contribute to a learning health care system by providing ongoing skill building, team training, and pilot funding for clinical and translational studies with a focus on integration of health care delivery and research. Increase the use and impact of clinical and research data to improve health by expanding Wake Forest’s strong informatics and scientific infrastructure and facilitating collaborations and multidisciplinary team science at CTSI and with CTSA Program network partners. Increase clinical and translational research opportunities to leverage CTSI’s expertise in multisite study support, recruitment of research participants and nationally prominent Nonhuman Primate Program in collaboration with the CTSA Program network. Increase the impact of clinical and translational research by engaging community and other relevant stakeholders and integrating their perspectives into all CTSI-supported activities. Promote research sustainability by increasing efficiency through effective organization, governance, collaboration and communication infrastructure combined with a comprehensive evaluation and continuous improvement process. CTSI achieves these goals through the activities of its 14 integrated programs, which support all clinical and translational research activities; provide training and education for caregivers, researchers and the community; and enhance the application of research to improve patient care and community health. Through its support of investigation, education and application, CTSI will capitalize on an integrated organizational structure to emerge as a learning health care system, connected effectively with the CTSA Program network. | ||||||||
| 3484 | Buffalo Clinical and Translational Science Institute | Principal Investigator Timothy Murphy, M.D., State University of New York at Buffalo Website The Buffalo Translational Consortium (BTC) is building a strong foundation for clinical and translational research in response to community needs. Fifty percent of Buffalo residents are underrepresented minorities who experienced health disparities in 2015. This statistic parallels the levels projected for the United States in 2050, making Buffalo a microcosm of what the nation may look like in 35 years. In 2012, the University at Buffalo opened a new Clinical and Translational Science Institute (CTSI), which includes translational research laboratories; a clinical research center; an imaging center; a laboratory animal facility; and a repository for archiving samples of blood, tissue and DNA from research participants. The University at Buffalo CTSI will enhance the research capabilities across the CTSA Program consortium by offering new health computational tools, new approaches to community-based research developed in collaboration with the local community, proven methods for sharing imaging data and drug development services. BTC will apply a unique tool for drug discovery — the Computational Analysis of Novel Drug Opportunities (CANDO) — to assess the activity of drugs or small molecules against protein targets. A particular strength of this CTSA Program hub is its community engagement initiatives. Plans are underway to expand research efforts focused on translation of research results into medical practice through BTC’s established networks and the Patient Voices Network, which includes patients as part of research teams. The Buffalo CTSI also will train and develop a diverse workforce to ensure that researchers and their teams have the skills and knowledge to advance translation. Training modules will be responsive to different learning styles and cultural backgrounds to meet the needs of a diverse clinical and translational research workforce. | ||||||||
| 3429 | 2015 ExRNA Projects: Biomarkers | NCATS is administering 18 new NIH Extracellular RNA (exRNA) Communication program projects as a next phase to test and validate exRNA molecules for their potential as disease biomarkers and treatments. Funded by the NIH Common Fund, these projects are aimed at developing clinically validated biomarkers. Circulating MicroRNAs as Disease Biomarkers in Multiple Sclerosis Clinical Utility of Extracellular RNA as Marker of Kidney Disease Progression Clinical Utility of MicroRNAs as Diagnostic Biomarkers of Alzheimer’s Disease Clinical Utility of Salivary ExRNA Biomarkers for Gastric Cancer Detection ExRNA Biomarkers for Human Glioma ExRNA Signatures Predict Outcomes After Brain Injury ExRNAs for Early Identification of Pregnancies at Risk for Placental Dysfunction Extracellular Non-Coding RNA Biomarkers of Hepatocellular Cancer Extracellular RNAs: Biomarkers for Cardiovascular Risk and Disease Plasma MiRNA Predictors of Adverse Mechanical and Electrical Remodeling After Myocardial Infarction Circulating MicroRNAs as Disease Biomarkers in Multiple Sclerosis Investigators: Howard L. Weiner, M.D., and Roopali Gandhi, Ph.D., Brigham and Women’s Hospital, Boston Grant Number: UH2-TR000890 Multiple sclerosis (MS) is a disease in which the body’s immune system attacks and destroys the protective covering of the nerves. Over time, the brain, the spinal cord and the rest of the body lose the ability to communicate with each other. Many people with MS eventually lose the ability to walk or speak clearly. MS affects 2.5 million people worldwide, including 400,000 in the United States. Currently, no cure exists, but some treatments can slow the disease. A better understanding of the biology and progression of MS could lead to better treatments or a cure. This study team previously measured a type of exRNA called microRNA (miRNA) in the blood of patients with MS and found that it was related to disease stage, response to therapy and level of disability. This project’s investigators will continue to study these biomarkers, or indicators of the presence, absence or stage of a disease, and assess their usefulness in diagnosing and monitoring MS progression and response to therapy. MiRNA biomarkers for MS may provide a new way for clinicians to better understand the nature of the disease in individual patients. Learn more about this project in the NIH RePORTER. Clinical Utility of Extracellular RNA as Marker of Kidney Disease Progression Investigators: Thomas Tuschl, Ph.D., The Rockefeller University, New York, and Manikkam Suthanthiran, M.D., Weill Cornell Medical College, New York Grant Number: UH2-TR000933 Chronic kidney disease (CKD) is a condition in which the kidneys partly or completely lose their ability to function and can result from high blood pressure, diabetes, disorders of the immune system, genetic defects and developmental disorders. CKD causes early death from heart disease, infections and cancer. Many CKD patients develop end-stage kidney disease and need dialysis or kidney transplants. Recipients of kidney transplants also are prone to CKD. Current tests cannot predict which patients will have CKD that worsens over time. Identifying CKD patients at risk for disease progression could allow clinicians to treat patients earlier and slow further decline in kidney function. It also could help scientists develop therapies that prevent decline in kidney function in patients at risk. This research team will identify types of exRNA in the urine of CKD patients and will determine whether this approach can identify patients at risk for worsening disease. The team plans to use these findings to develop a urine test that clinicians can use to guide treatment of CKD patients. Learn more about this project in the NIH RePORTER. Clinical Utility of MicroRNAs as Diagnostic Biomarkers of Alzheimer’s Disease Investigators: Julie Anne Saugstad, Ph.D., and Joseph M. Quinn, M.D., Oregon Health and Science University, Portland Grant Number: UH2-TR000903 Alzheimer’s disease (AD) is the most common form of dementia and is the sixth leading cause of death in the United States. AD symptoms include memory loss, personality changes and trouble thinking, and the disease typically worsens over time. Current AD treatments cannot stop the disease from progressing, but they can slow the development of symptoms temporarily. Currently, clinicians diagnose AD by noting the degree of a patient’s mental decline, which is not obvious until severe and permanent brain damage has occurred. No biomarkers exist that can be used to predict the onset of AD or distinguish early AD from age-related memory loss. ExRNA could have an important role as a diagnostic biomarker for AD. This project team will examine miRNA found in the fluid surrounding the brain and spinal cord for its usefulness as a biomarker to diagnose AD earlier. Earlier diagnosis could allow patients to start treatments sooner, possibly slowing or preventing brain function decline and damage. Learn more about this project in the NIH RePORTER. Clinical Utility of Salivary ExRNA Biomarkers for Gastric Cancer Detection Investigator: David T.W. Wong, D.M.D., D.M.Sc., University of California, Los Angeles Grant Number: UH2-TR000923 Gastric (stomach) cancer kills about 800,000 people worldwide each year. This cancer is quite deadly because most people do not notice symptoms until the disease has advanced. Studies suggest that exRNA in saliva can be used as a biomarker to detect oral cancer, Sjögren’s syndrome (a disease in which immune cells attack and destroy the glands that produce tears and saliva), pancreatic cancer, breast cancer, lung cancer and ovarian cancer. This project team will study exRNA in saliva to determine its usefulness as a biomarker for gastric cancer. The study will compare exRNA in saliva from people with and without gastric cancer to assess which types of exRNA are specific to gastric cancer. The use of exRNA in saliva as a biomarker of gastric cancer could enable clinicians to perform simple tests to detect and treat gastric cancer at earlier stages. Learn more about this project in the NIH RePORTER. Read an NCATS feature story about this research. Left: ExRNA saliva experts Xinshu (Grace) Xiao, Ph.D., and David T. W. Wong, D.M.D., D.M.Sc. Right: Mechanism of salivary exRNA development in pancreatic cancer. (A) Pancreatic cancer sheds exosomes carrying tumor-specific RNAs shuttled from the pancreas to the salivary glands. (B) Exosomes move through small cavities called acini in the salivary glands. (C) During swallowing, salivary exosomes travel to the gastrointestinal tract. (University of California, Los Angeles Photos/Reed Hutchinson) ExRNA Biomarkers for Human Glioma Investigators: Bob S. Carter, M.D., Ph.D., University of California, San Diego, and Fred Hochberg, M.D., Massachusetts General Hospital, Boston Grant Number: UH2-TR000931 Gliomas are the most common type of brain tumor and, when malignant, require care that poses an economic and emotional burden to many individuals. The tumors are hard to diagnose and treat. Surgeons use biopsies to provide diagnoses, but many patients cannot sustain an operation or obtain benefit, as surgery requires removal of brain tissue responsible for language or movement. These investigators will change patient care by providing diagnoses of malignant and benign gliomas, without surgery, based on “liquid biopsies” of blood and fluid covering the brain. Working with a consortium composed of 20 American brain surgeons, the investigators have developed techniques to characterize small amounts of exRNA within exosomes that are released by brain tumors. By using state-of-the-art technologies, they can identify the exRNA without surgery but with a high degree of accuracy. This approach sets the stage for “personalized medical care” of brain tumor patients. This research could lead to safer, less expensive forms of diagnosis and a more rapid, personalized, effective treatment of brain tumors. Findings from this research also could be used to improve scientists’ understanding of risk factors for gliomas, improve how patients respond to brain tumor treatments and create a roadmap of therapies for patients. Learn more about this project in the NIH RePORTER. This series of images illustrate how exRNA biomarkers in plasma and cerebrospinal fluid aid diagnosis of brain tumors. The first illustration (a) is a drawing of a head and neck, with the brain and spine. A glioma is indicated by an oval within the brain. Arrows pointing out of the glioma indicate that it releases exRNA contained in exosomes (presented as circles with wavy lines inside) into the brain and spinal fluid. An illustrated inset (b) shows several exosomes and exRNA molecules in the cerebrospinal fluid. Another inset (c) shows a microscope image of exosomes containing exRNA. A syringe points to the cerebrospinal fluid in inset b, representing the method by which exosomes are isolated for diagnostic testing. Another illustration (d) shows an exRNA diagnostic test with a panel of five biomarkers, labeled A–E, with negative and positive test results for glioma. Using exRNA in this diagnostic manner represents a form of personalized therapy. (University of California at San Diego Photo) ExRNA Signatures Predict Outcomes After Brain Injury Investigators: Kendall Van Kueren-Jensen, Ph.D., and Matthew J. Huentelman, Ph.D., Translational Genomics Research Institute, Phoenix; P. David Adelson, M.D., Phoenix Children’s Hospital; and Robert Spetzler, M.D., St. Joseph’s Hospital and Medical Center, Phoenix Grant Number: UH2-TR000891 Intracranial hemorrhage (ICH) ― bleeding in the brain ― is most often caused by head injuries or strokes. These life-threatening conditions can severely damage brain tissue and often leave patients disabled. Scientists still do not fully understand what goes wrong in the brain during and after these events. A biomarker to detect patients at risk for poor outcomes following ICH could lead to better treatments while improving understanding of the biology of the disease. Certain types of exRNA may be used as biomarkers to predict how patients will respond after ICH. The investigators will identify exRNA biomarkers that can indicate presence of injury and predict a patient’s outcome after ICH. Ultimately, this research could allow for earlier and better treatments and outcomes in patients as well as improved understanding of the disease biology. Learn more about this project in the NIH RePORTER. Intracerebral hemorrhage (ICH) causes 15 percent of all strokes. Three ICH types are shown in this figure. (1) Subarachnoid hemorrhage occurs when a weakened spot on one of the brain’s blood vessels balloons and breaks, leaking blood into the subarachnoid space, which leads to secondary injuries including potential stroke as nearby blood vessels narrow. (2) Intraparenchymal hemorrhage, which is typically caused by high blood pressure in adults or abnormal development of a key area of the brain in infants, creates unhealthy deposits of blood and blood breakdown products in the brain. (3) Intraventricular hemorrhage extends into the ventricular spaces of the brain and results in hydrocephalus (buildup of fluid in the brain) and injury to brain tissue. (Copyright 2015 Barrow Neurological Institute) ExRNAs for Early Identification of Pregnancies at Risk for Placental Dysfunction Investigator: Louise C. Laurent, M.D., Ph.D., University of California, San Diego Grant Number: UH2-TR000906 Placental dysfunction occurs when too little blood, carrying oxygen and nutrients, flows from the mother to the fetus in the womb. The condition can cause poor growth of the fetus and dangerously high blood pressure in the mother during pregnancy. Placental dysfunction is a major cause of maternal and fetal disability and death worldwide. Scientists believe that abnormal cell growth and activity in the placenta during the first trimester of pregnancy causes placental dysfunction. However, clinicians usually do not detect placental dysfunction until the late second and third trimesters. Early detection of pregnancies at risk for this disorder would help clinicians prevent or better treat it. This project’s investigators aim to develop such a method by examining whether exRNA in the blood could be used as a biomarker of risk for placental dysfunction. Accurately determining a woman’s risk would enable clinicians to identify high-risk patients so that high blood pressure or poor growth of the fetus can be detected earlier while sparing low-risk patients unnecessary anxiety. Learn more about this project in the NIH RePORTER. Extracellular Non-Coding RNA Biomarkers of Hepatocellular Cancer Investigator: Tushar Patel, M.B., Ch.B., Mayo Clinic, Jacksonville, Florida Grant Number: UH2-TR000884 Hepatocellular carcinoma (HCC), the most common type of liver cancer, is becoming more prevalent, yet survival remains poor. The earlier HCC is diagnosed, the better a patient’s chance for survival. Unfortunately, current tests for HCC are not very good at detecting the cancer early enough for clinicians to treat it effectively. HCC cells release several types of exRNA within exosomes, tiny particles produced by most cells that carry exRNA through body fluids. This project is designed to determine whether this exRNA can be used as a biomarker to indicate the presence of HCC in a patient. The investigator also aims to develop a clinically useful way to detect and measure these potential biomarkers and determine their usefulness in identifying patients with HCC earlier than current methods allow. Learn more about this project in the NIH RePORTER. Extracellular RNAs: Biomarkers for Cardiovascular Risk and Disease Investigator: Jane E. Freedman, M.D., University of Massachusetts Medical School, Worcester Grant Number: UH2-TR000921 Cardiovascular disease (CVD) is the leading cause of death in the United States. Heart disease and stroke, the most common forms of CVD, have common risk factors, including high blood pressure, diabetes, obesity, cigarette smoking and high cholesterol. Certain types of exRNA in the blood affect development and progression of CVD. Researchers have found connections between some of this exRNA and specific forms of CVD. The amounts and types of exRNA may change over time or due to the presence of certain CVD risk factors. Different types of this exRNA could be useful as biomarkers to predict CVD events. To test this possibility, the project team will use blood samples to look for links between exRNA and the presence of CVD. The investigators ultimately will attempt to develop a quick and effective blood test for CVD and its risk factors, using exRNA as a biomarker. Learn more about this project in the NIH RePORTER. Plasma MiRNA Predictors of Adverse Mechanical and Electrical Remodeling After Myocardial Infarction Investigators: Saumya Das, M.D., Ph.D., and Anthony Rosenzweig, M.D., Beth Israel Deaconess Medical Center, Boston; and Raymond Y. Kwong, M.D., M.P.H., and Marc Sabatine, M.D., M.P.H., Brigham and Women’s Hospital, Boston Grant Number: UH2-TR000901 Each year, complications from heart attacks (also called myocardial infarctions) contribute to more than half a million cases of heart failure and 300,000 cases of sudden cardiac arrest, due to lethal arrhythmias. Both of these conditions are closely related to changes in the structure and function of the heart — called remodeling — that follow a heart attack. Current tests to predict which patients are at risk for these complications are not accurate enough. This team of investigators will (1) identify exRNA that are related to poor heart remodeling, (2) assess the functionality and prognostic ability of exRNA signatures in animal models of heart disease, and (3) determine whether exRNA signatures can predict which patients are at risk for poor health outcomes after heart attacks. This test could replace current tests by more accurately identifying patients at higher risk and in need of more frequent monitoring and medical care. Learn more about this project in the NIH RePORTER. This figure illustrates aspects of cardiovascular disease and its biomarkers and shows how the Das Group united clinical, translational and basic science for clinically relevant, mechanistic biomarker discovery in this disease model. The figure includes an image showing a fluorescence microscopy picture of a heart cell. Marked in the picture are symbols for injury and release of exRNA from the injured cell. An arrow points from this image to results from two magnetic resonance imaging scans of hearts, one with a myocardial scar from a heart attack and the other with cardiac remodeling/heart failure. The image to the right of the heart cell shows a graph depicting differing exRNA expression between good and poor remodeling patients. An arrow points from this graph to an electrocardiogram (EKG) readout indicating sudden cardiac arrest. Another arrow points from the central heart cell and exRNA expression images to a graph of clinical outcomes. Taken together, these images signify that exRNA molecules released from the heart are important in mechanical remodeling (MRI) and electrical remodeling (EKG) and ultimately translate into clinical outcomes in patients with cardiovascular disease. (Ravi Shah, Saumya Das, Yaw Poku Photo) | ||||||||
| 3428 | 2015 ExRNA Projects: Therapies | NCATS is administering 18 new NIH Extracellular RNA (exRNA) Communication program projects as a next phase to test and validate exRNA molecules for their potential as disease biomarkers and treatments. Funded by the NIH Common Fund, these projects are aimed at advancing exRNA-based therapies to the point where Investigational New Drug applications can be filed with the Food and Drug Administration to launch human studies. Exosome-Based Therapeutics in Huntington’s Disease Exosome RNA — Therapeutics to Promote Central Nervous System Myelination Fruit Exosome-Like Particles for Therapeutic Delivery of Extracellular miRNAs HER2-Targeted Exosomal Delivery of Therapeutic mRNA for Enzyme Pro-Drug Therapy Novel Extracellular RNA-Based Combinatorial RNA Inhibition Therapy Regulation of Renal and Bone Marrow Injury by Extracellular Vesicle Non-Coding RNA Targeted Delivery of MicroRNA-Loaded Microvesicle for Cancer Therapy Targeting Tumor-Derived exRNA-Containing Microvesicles by High-Throughput Screening Exosome-Based Therapeutics in Huntington’s Disease Investigator: Neil Aronin, M.D., University of Massachusetts Medical School, Worcester Grant Number: UH2-TR000888 Huntington’s disease is an inherited disorder that causes memory and thinking problems, abnormal movements, and depression. The disease usually starts in adults between the ages of 30 and 40 and worsens throughout a person’s life. People with Huntington’s disease eventually become unable to take care of themselves and often must live in costly nursing facilities. Huntington’s disease is caused by a change, or mutation, in the gene that codes for a protein called huntingtin. The mutation causes the body to make abnormal versions of the huntingtin protein, which damages brain cells and produces symptoms of the disease. In animal models of Huntington’s disease, a type of exRNA called small interfering RNA (siRNA), when injected into the brain, can block production of the abnormal huntingtin protein, reducing symptoms of the disease. However, clinicians must directly inject this substance into the brain, which is not an ideal delivery method in humans. In this project, investigators will inject exosomes — tiny particles produced by most types of cells that can contain and transport exRNA — into the blood of mice with Huntington’s disease. The exosomes will travel through the blood to deliver the therapeutic siRNA to the brain. Eventually, researchers could use these siRNA-containing exosomes to treat humans with Huntington’s disease and to develop treatments for other brain diseases. Learn more about this project in the NIH RePORTER. Exosome RNA — Therapeutics to Promote Central Nervous System Myelination Investigator: Richard P. Kraig, M.D., Ph.D., University of Chicago Grant Number: UH2-TR000918 Multiple sclerosis (MS) is a disease in which the body’s immune system attacks and destroys the protective covering of the nerves, called the myelin sheath, through a process called demyelination. Over time, the brain, the spinal cord and the rest of the body lose the ability to communicate. Many people with MS eventually lose the ability to walk or speak clearly. MS affects about 2.5 million people worldwide, including 400,000 in the United States. Current MS therapies can slow the disease by reducing demyelination, but no treatment exists to restore the lost myelin, called remyelination. Research has shown that exosomes that contain a type of exRNA called microRNA (miRNA) can trigger remyelination. The investigators plan to develop exosomes containing miRNA as a therapy for brain remyelination and treatment of MS. Learn more about this project in the NIH RePORTER. This figure is a series of illustrations that show how exRNA molecules released from immune cells can enhance myelination and thus counteract the de-myelinating effects of conditions including aging, migraine and MS. A mouse running on a wheel represents environmental enrichment (EE), which triggers immune cells to release exosomes containing microRNA-219 (miR-219) into the bloodstream (depicted by a blood vessel containing circular exosomes in the blood). Similarly, this effect can be mimicked in cultured dendritic cells (depicted by a drawing of a dendritic cell in a petri dish releasing circular exosomes) by stimulating them with interferon gamma. The figure shows that through either method, exosomes containing miR-219 cross the blood-brain barrier and interact with a precursor cell in the brain. In the next part of the figure, these precursors become mature myelinating cells. The figure shows that migraine, aging and MS block this myelinating process. These stimulated dendritic cell exosomes could represent a novel therapeutic for MS, migraine and other neurodegenerative diseases associated with myelin loss. (University of Chicago Photo) Fruit Exosome-Like Particles for Therapeutic Delivery of Extracellular miRNAs Investigators: Huang-Ge Zhang, M.D., D.V.M., Ph.D., University of Louisville, Kentucky, and Peixuan Guo, Ph.D., University of Kentucky, Lexington Grant Number: UH2-TR000875 Exosomes from mammals can deliver drugs for chemotherapy. This method is not ideal because it is hard to produce the large numbers of exosomes needed and because a patient’s immune system could reject the exosomes. Researchers can, however, remove large amounts of edible exosome-like particles from grapes. These exosomes can transport chemotherapy drugs. Scientists can alter the exosomes so that they can travel to the brain and, when given orally, to the liver. This research team will determine whether these exosomes can deliver therapeutic miRNA to cancerous cells of the colon, breast and brain. The team also will determine whether it is possible to produce large amounts of exosomes inexpensively for use in the clinic. The scientists hope to create a therapeutic delivery system that can be used more widely both for research and for treatment. Learn more about this project in the NIH RePORTER. A research team led by Huang-Ge Zhang, Ph.D., at the University of Louisville has shown that large amounts of exosome-like particles from grapes and other edible plants can deliver therapeutic miRNA and chemotherapy drugs for potential treatment of cancer. Zhang is shown on the left in a laboratory holding a dish of red grapes; on the right is a microscopic image of exosome-like particles from grapes. (University of Louisville Photo) HER2-Targeted Exosomal Delivery of Therapeutic mRNA for Enzyme Pro-Drug Therapy Investigator: A.C. Matin, Ph.D., Stanford University, California Grant Number: UH2-TR000902 HER2-positive breast cancer is an aggressive type of breast cancer that responds poorly to treatment because the cancer cells produce a protein that promotes tumor growth. The investigators plan to enhance the natural ability of exosomes to transport molecules by attaching them to a new drug that targets and kills HER2-positive breast cancer cells. The drug also becomes fluorescent when it attacks the cancer cells, so researchers can see it within a living animal. The research team will load exosomes with this drug and test it in animals. The team aims to develop a more effective treatment for aggressive HER2-positive breast cancer and improve outcomes for patients with this disease. Learn more about this project in the NIH RePORTER. Novel Extracellular RNA-Based Combinatorial RNA Inhibition Therapy Investigators: Anil K. Sood, M.D., George A. Calin, M.D., Ph.D., and Gabriel Lopez-Berestein, M.D., University of Texas M.D. Anderson Cancer Center, Houston Grant Number: UH2-TR000943 Ovarian cancer is the most deadly cancer of the female reproductive system. Because women usually have mild or no symptoms during the cancer’s early stages, it is often not diagnosed until it has spread to other organs in the body. By the time the cancer is advanced, treatments are effective only for short periods. One type of miRNA can enter ovarian cancer cells and enhance their growth. The investigators will develop a new treatment approach that removes this cancer-promoting miRNA from human tumor cells and blocks additional miRNA from entering them. Researchers could add this method to current ovarian cancer treatments to enhance their effects. The methods developed will apply to the treatment of many cancers. Learn more about this project in the NIH RePORTER. Regulation of Renal and Bone Marrow Injury by Extracellular Vesicle Non-Coding RNA Investigator: Peter J. Quesenberry, M.D., Rhode Island Hospital, Providence Grant Number: UH2-TR000880 Microvesicles are tiny particles that contain exRNA, are produced by most types of cells, and can contain and transport various types of exRNA through the body. Microvesicles from stem cells can heal injured kidney and bone marrow tissue by delivering a therapeutic type of exRNA called non-coding RNA. For this project, investigators will search for non-coding RNA in microvesicles from stem cells that can heal injured kidney and bone marrow stem cells. The investigators then will develop a way to deliver the non-coding RNA to help injured kidney or bone marrow tissue regrow. This study could lead to the development of non-coding RNA therapy for bone marrow diseases and kidney damage in humans. Learn more about this project in the NIH RePORTER. Targeted Delivery of MicroRNA-Loaded Microvesicle for Cancer Therapy Investigators: Thomas D. Schmittgen, Ph.D., and Mitch A. Phelps, Ph.D., The Ohio State University, Columbus Grant Number: UH2-TR000914 Hepatocellular carcinoma (HCC) is the most common form of liver cancer and the third deadliest cancer, causing 1 in 10 cancer deaths worldwide. No effective therapy exists, and patients with advanced HCC ultimately die from the disease. Certain types of miRNA can block HCC tumor cell growth and represent a potential treatment for this deadly disease. However, miRNA is expensive to develop, degrades rapidly and is potentially toxic to healthy tissues, so development of miRNA-based therapies has been challenging. To address these problems, the investigators will develop naturally produced miRNA and package it into microvesicles that protect the miRNA and direct it to HCC tumors. The research team will program cells grown in the laboratory to produce the miRNA-loaded microvesicles. Then they will remove the microvesicles from the cells and test them in animals with HCC. Eventually, these microvesicles could be tested in HCC patients. This technology also could be used in the future to deliver other types of RNA drugs for a variety of other cancers and diseases. Learn more about this project in the NIH RePORTER. Targeting Tumor-Derived ExRNA-Containing Microvesicles by High-Throughput Screening Investigator: Asim Abdel-Mageed, D.V.M., M.S., Ph.D., Tulane University School of Medicine, New Orleans Grant Number: UH2-TR000928 Castration-resistant prostate cancer (CRPC) is cancer of the prostate gland that continues to grow despite treatments that stop the body from using testosterone, a hormone that some tumors rely on for growth. Unraveling the biology of tumor growth and spread is critical to developing treatments for CRPC. Recent findings show that certain types of exRNA released by CRPC tumors appear to cause further tumor growth. This exRNA is contained in microvesicles. Drugs that target and destroy these microvesicles could slow or stop tumor growth. This project will test thousands of already approved drugs for the ability to block the activity of microvesicles and slow the growth of tumors in cell cultures and animals. Testing already approved drugs reduces the time and high cost of drug development, allowing promising drug candidates to be used in patients sooner. Learn more about this project in the NIH RePORTER. | ||||||||
| 3430 | Researchers Working to Advance ExRNA Biomarkers and Therapies | Cells in the human body release a type of signaling molecule called extracellular RNA (exRNA) that can travel through body fluids to communicate information to distant cells. NIH-funded researchers are exploring the use of exRNAs as biomarkers, or indicators of the presence, absence or stage of a disease. In addition, researchers hope to use exRNAs to develop molecular treatments for many diseases. NCATS has announced it will spearhead the second phase of several NIH ExRNA Communication program projects to test and validate exRNA molecules for their potential as disease biomarkers and treatments. The first phase of these NCATS projects focused on discovery and feasibility. The NCATS projects are funded by the NIH Common Fund. “Although still in its early days, exRNA communication is an example of a game-changing discovery that could revolutionize the field of translational science,” said NCATS Director Christopher P. Austin, M.D. ExRNA molecules have many biological functions and may play an important role in a wide range of diseases, including different types of cancer and neurological disorders, among others. Researchers are using exRNA biomarkers in some of the projects to diagnose a variety of conditions and to predict their progression in patients. Others are exploring new ways to use exRNAs as clinical therapeutic treatments for illnesses. For example, therapeutic exRNA molecules could be delivered inside exosomes ― tiny particles produced by cells that can contain and transport exRNA ― to targets for many diseases. Specific focus areas include: Alzheimer’s disease; Multiple sclerosis; Kidney disease; Brain injury; Pregnancy complications; Heart disease, heart attack and stroke; and Liver, stomach and brain cancers. “During the first two years of the program, we confirmed that exRNA is not just a bystander molecule, but that it exerts important effects in the body,” said Danilo A. Tagle, Ph.D., M.S., associate director for special initiatives at NCATS. “We hope to use exRNA biomarkers and therapies to potentially address a wide range of diseases and improve the health and well-being of patients.” The funded exRNA researchers disseminate data and resources via the exRNA Research Portal to keep the scientific community informed of the most recent developments in the field. In addition to NCATS, the NIH team leading the exRNA communication effort includes the National Cancer Institute; National Heart, Lung, and Blood Institute; and National Institute on Drug Abuse. Learn more about NCATS’ participation in the ExRNA Communication program. The NIH Common Fund provides more information about the exRNA consortium. Posted September 2015 | ||||||||
| 3424 | Kaufmann Appointed Head of NCATS’ Office of Rare Diseases Research | Will Retain Role as NCATS’ Division of Clinical Innovation Director On Sept. 3, 2015, NCATS Director Christopher P. Austin, M.D., named Petra Kaufmann, M.D., M.Sc., as director of the Center’s Office of Rare Diseases Research (ORDR). Kaufmann’s new leadership role will include overseeing NCATS’ Rare Diseases Clinical Research Network (RDCRN), the Genetic and Rare Diseases Information Center, and the NIH/NCATS Global Rare Diseases Patient Registry Data Repository/GRDR® program. She will retain her current position, held since May 2014, as director of NCATS’ Division of Clinical Innovation (DCI), which includes the Clinical and Translational Science Awards (CTSA) Program. “Research on rare diseases has advanced into the mainstream as an area of disproportionate medical need, a basis of insights into common diseases, an avenue to identify commonalities among diseases and a testing ground for new translational approaches — all of which are accelerating the translational science process,” Austin said. “Because of shared science and shared goals among NCATS’ ORDR and DCI programs, placing them both under one person’s leadership will enhance synergy, increase our Center’s ability to advance translational science and help bring more treatments to more patients more quickly.” Kaufmann has had a longstanding interest in and commitment to rare diseases research. She is deeply involved in the rare diseases community and has a distinguished track record leading rare disease programs and complex collaborations in academia and government. Her training and experience span neurology, biostatistics, clinical research and clinical trials. “I am delighted with this new opportunity to bring the rare diseases community and the broader clinical and translational community together,” Kaufmann said. “I am optimistic that we can make great progress in advancing research to respond to the needs of the millions of people living with rare diseases through collaboration among our grantees, staff, patient advocacy organizations, industry, NIH colleagues and other federal agencies.” Prior to joining NCATS, Kaufmann was at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), where she directed the Office of Clinical Research and initiated NeuroNEXT, a network for neurological trials. Before coming to NIH in 2009, Kaufmann was a tenured associate professor of neurology at Columbia University in New York City, where she worked in the neuromuscular division, electromyography laboratories and pediatric neuromuscular clinic. Kaufmann also has worked on natural history studies, biomarker development and clinical trials in amyotrophic lateral sclerosis, muscular dystrophies, spinal muscular atrophy and mitochondrial disorders. ORDR was established in 1993 within the NIH Office of the Director under the leadership of Stephen C. Groft, Pharm.D. In 2011, ORDR became part of the newly established NCATS. ORDR guides and coordinates NIH-wide activities involving research for a broad array of rare diseases, responds to research opportunities for rare diseases, and provides information on rare diseases. Groft served as director of ORDR until his retirement in February 2014. Posted September 2015 | ||||||||
| 3421 | Stem Cell Translation Laboratory (SCTL) | The SCTL utilizes the latest technology and techniques in stem cell research to investigate innovative methodologies for accelerating the therapeutic development process. OverviewThe progress made in stem cell biology over the past decade has opened many new opportunities for basic and translational scientists worldwide. Induced pluripotent stem cells (iPSCs) are particularly useful because scientists can group them into many specialized cell types to use for research or regenerative medicine applications (e.g., cell and gene therapy).Scientists produce iPSCs by reprogramming adult cells (e.g., skin cells, blood cells) to an embryonic stem cell–like state, where they have the potential to become any cell type of the human body. iPSC-based therapies are ideal because they use a patient's own cells, preventing such potential complications as rejection by the immune system. In addition, scientists can use iPSCs to produce the large amounts of relevant cells (e.g., nerve cells, liver cells) needed for disease research, tissue engineering, toxicology and regenerative medicine. Major limitations that currently impede the application of iPSCs include the lack of highly reproducible and well-defined procedures required to generate, characterize and differentiate patient-specific iPSCs safely for preclinical and clinical use.YouTube embed video: https://www.youtube-nocookie.com/embed/zAx6g5zcfXgTake a virtual tour of the NCATS Stem Cell Translation Laboratory.About the LabTo establish and move stem cell technologies forward through a more centralized effort, NIH has launched the Stem Cell Translation Laboratory (SCTL) within NCATS. Initially part of the NIH Common Fund's Regenerative Medicine Program, the goal of the SCTL is to bring iPSC technology closer to clinical applications and drug development. Through the SCTL, NCATS provides researchers across various disciplines and organizations access to innovative protocols and resources to advance the translation of regenerative medicine applications. Through a multidisciplinary collaborative team approach, NCATS' SCTL scientists aim to:1. Establish quality control (QC) standards to define pluripotency and differentiated cell types2. Develop methods to assess heterogeneity and characterize iPSC-derived cells using multi-omics technologies3. Develop standardized methods to produce mature and functional cells meeting the QC standards above4. Discover, validate and disseminate small-molecule reagents to replace expensive recombinant proteins, xenogeneic material and undefined media components in cell differentiation protocols ContactCarlos A. Tristan, Ph.D. | ||||||||
| 3423 | Common Data Elements (CDEs) | CDEs enable information to be collected and presented in consistent formats to ensure data from different sources are defined in the same way using the same standards and vocabulary. A CDE consists of both a precisely defined question and a specified format or set of permissible responses. Each CDE represents a variable that can be collected and analyzed in projects and registries within a particular analytic or clinical domain. Researchers can combine sets of CDEs consisting of individual question-answer pairs into more complex questionnaires, survey instruments and case report forms for use in collecting data for research, patient registries and surveillance studies. GRDR® program staff have developed a model registry of CDEs (Excel - 49KB) for entry of patient data into any rare disease registry. These CDEs are not intended to address all the needs of a specific rare disease registry; rather, the CDEs are designed to capture information at a minimum level of detail that is needed for all or most rare diseases studies. This model can be modified and tailored according to the specific needs of the registry. The GRDR program CDEs include a subset of CDEs that do not include personal information that could identify the patient. The GRDR CDEs are organized into 10 categories that include required and optional elements: Current contact information Sociodemographic information Diagnosis Family history Birth and reproductive history Anthropometric (body measurement) information Patient-reported outcomes Medications, devices and health services Clinical research participation and biospecimen donation Communication and preferences The list of GRDR CDEs will continue to expand to include new CDEs and validated disease-specific elements for data entry by patients, clinicians, other health care professionals and researchers. All future recommended GRDR CDEs will be established in collaboration with NIH Institutes and Centers and other professional patient organizations involved in CDE development. Learn more about CDE initiatives within NIH and other federal agencies or explore NIH’s CDE collection. | ||||||||
| 3422 | Global Unique Identifier (GUID) | Data submitted through NCATS’ GRDR® program is de-identified so that patients’ personally identifiable information (PII) is not exposed to NCATS staff and researchers. Individuals submitting de-identified data must code them using a random number known as a Global Unique Identifier (GUID), a computer-generated alphanumeric code that is unique to each research participant. Because the GUID is not generated from personal information, it enables data from a de-identified subject to be integrated; tracked over time; and linked across projects, databases and biobanks. Through the GRDR program, NCATS provides complimentary software that registry owners can download to generate the GUID. To use the tool, registry owners submit the following information: Complete legal given first, middle and last names of subject at birth Date of birth Name of city/municipality in which subject was born Country of birth Physical sex of subject at birth (optional) Using this information, the software generates a random number (GUID) and sends it to the GRDR. In other words, PII is never actually transferred to the GRDR or stored within the GRDR database. Registry owners can access the GRDR GUID software or request a new account. GUID Videos YouTube embed video: https://www.youtube.com/watch?v=UAOGarUAarw Watch an overview of the GUID tool and the GUID creation process, including elements required to generate a GUID. YouTube embed video: https://www.youtube.com/watch?v=b2C_kbJulng Watch a brief tutorial that demonstrates, step-by-step, how to access the GRDR GUID tool, how to create a GUID and how to upload information to generate a group of GUIDs. |
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