Director's Message
We all know that chemicals can be helpful or harmful to our health, but the systems we have for evaluating those effects are, like so many aspects of translational research, inefficient and often ineffective. Chemicals can be more than just life-saving (e.g., penicillin) or life-ending (e.g., cyanide). For example, the drug warfarin is effective both at preventing stroke in humans and at killing rats, depending on the context and the dose.
Toxicity — a chemical's ability to produce harmful effects in animals or humans — causes nearly one-third of drug development failures and can produce harmful health effects from chemicals in the environment. Scientists cannot tell in advance whether a compound is toxic because they usually don't know how it affects the molecules and cells of the body. Better prediction methods and models would improve the speed, efficiency and accuracy of chemical testing and thus improve public health.
One way NCATS is working to improve understanding and prediction of toxicity is through an initiative called Toxicology in the 21st Century, or Tox21. In Tox21, NCATS works with collaborators at the Environmental Protection Agency (EPA), the National Toxicology Program at the National Institute of Environmental Health Sciences (NIEHS) and the Food and Drug Administration (FDA) to test 10,000 drugs and environmental chemicals for their potential to cause health problems. The Tox21 team uses that information to develop computer models that will predict toxicity problems in advance. High-speed robots in the NCATS Division of Pre-Clinical Innovation are testing the compounds in collaboration with NIEHS, EPA and the FDA.
One of the most effective ways to drive scientific progress is to release data publicly so that all researchers can use the information. This month, two NCATS programs announced major data releases. First, all Tox21 results were made available in the National Library of Medicine's PubChem database and in public NIEHS and EPA databases. Just yesterday, EPA announced the release of new toxicity data on 1,800 chemicals from its ToxCast library, which is part of the Tox21 library of 10,000 chemicals. The scientific community can access the data through an online tool and participate in challenges designed to find innovative ways to predict negative health effects using the new data.
Also this month, NCATS and collaborators at Life Technologies Corp. made gene-silencing data on the biochemical makeup of small interfering RNA molecule libraries available to the public for the first time. Scientists use these molecules, which can selectively block the activity of genes, in RNA interference (RNAi) research to better understand how genes function in disease. We anticipate that access to this critical new class of data will be catalytic to translational efforts around the world.
Finally, this month we announced a new addition to my leadership team: Pamela McInnes, D.D.S., M.Sc.(Dent.), who will become deputy director of NCATS on Jan. 12, 2014. Pamela will be a crucial part of NCATS' success in the years to come. In this issue of the e-newsletter, you can learn more about these and other exciting NCATS developments, including how RNAi technology helped uncover potential therapeutic targets for Parkinson's disease and how large-scale data sets increase the potential of finding new treatments for patients.
Best wishes for the rest of the holiday season, and thank you for your interest in NCATS' work.
Sincerely,
Christopher P. Austin, M.D.
Director
National Center for Advancing Translational Sciences
What's New at NCATS?
Pamela M. McInnes Named NCATS Deputy Director
NCATS Video: Improving Health Through Smarter Science
Gene-Silencing Data Released, NCATS Technology Reveals New Targets for Parkinson's Disease
Toxicity Data and Challenges for NCATS-Tested Chemicals Now Available Online
NCATS Director Speaks at Partnering for Cures Meeting
New BrIDGs Projects Announced to Help Accelerate Therapeutic Development
Understanding the Brain's Response to Sugar Could Help Treat Obesity
NCATS Science Featured at 27th NIH Research Festival
Collaborate with NCATS Scientists
Pamela M. McInnes Named NCATS Deputy Director
Pamela M. McInnes, D.D.S., M.Sc.(Dent.), will become NCATS' deputy director on Jan. 12, 2014. With more than 25 years of NIH experience, McInnes brings a wealth of knowledge and expertise in clinical and translational research, extramural management, trans-NIH collaborations and public-private partnerships, making her an ideal fit for the Center.
"I am thrilled that Pamela is joining the NCATS leadership team," said NCATS Director Christopher P. Austin, M.D. "Her recruitment is a key milestone in our building NCATS into a catalyst for transformational change in translational science to get new treatments to more patients more quickly."
Currently, McInnes serves as director of the Division of Extramural Research at the National Institute of Dental and Craniofacial Research. There, she is responsible for all of the institute's extramural research, which ranges from basic through clinical research, including large and complex clinical and population-based trials. She is committed to the rigorous and robust conduct of clinical trials that adhere to the highest standards for human subject protection and data integrity. Her work in translational sciences has led to numerous product development and clinical evaluation programs, and she is actively involved in efforts to reduce death and disease with the broader extramural research community.
Read more in the NIH news release.
NCATS Video: Improving Health Through Smarter Science
NCATS recently released its first video in a planned series about the Center. "NCATS: Improving Health Through Smarter Science" features an overview of NCATS' work to overcome roadblocks in the translational research process.
In addition to NCATS Director Christopher P. Austin, M.D., several stakeholders appear in this five-minute video. Todd Sherer, Ph.D., chief executive officer of the Michael J. Fox Foundation for Parkinson's Research, outlines how NCATS is identifying translational research barriers and developing solutions that can be applied to many diseases. Pfizer's chief medical officer, Freda Lewis-Hall, M.D., explains NCATS' role within the drug discovery process, and Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, describes how NCATS is working with other NIH institutes and centers to move their research forward.
Watch the full video to learn more, and look for additional videos in the series on NCATS' YouTube channel.
Gene-Silencing Data Released, NCATS Technology Reveals New Targets for Parkinson's Disease
On Dec. 11, 2013, NIH announced that, for the first time, large-scale information on the biochemical makeup of small interfering RNA (siRNA) molecules is available publicly. Scientists use these molecules, which can selectively inhibit gene activity, in RNA interference (RNAi) research to better understand how genes function in disease. Making these data accessible to researchers worldwide increases the potential of finding new treatments for patients.
RNAi researchers at NCATS collaborated with Life Technologies Corp., which owns the siRNA molecules, to make the data release possible.
"Producing and releasing these data demonstrate NCATS' commitment to speeding the translational process for all diseases," said NCATS Director Christopher P. Austin, M.D. "The Human Genome Project showed that public data release is critical to scientific progress. Similarly, I believe that making RNAi data publicly available will revolutionize the study of biology and medicine."
By harnessing the power of RNAi to study the function of many individual genes, researchers can identify links to particular diseases. Just last month, a team of NIH scientists led by Richard Youle, Ph.D., of the National Institute of Neurological Disorders and Stroke, and NCATS' Scott Martin, Ph.D., used RNAi to find genes linked to Parkinson's disease, a devastating movement disorder. The genes could represent new starting points for developing better treatments. The study results were published online in the Nov. 24, 2013, issue of Nature.
Read NIH news releases on the siRNA data and the Parkinson's study.
Toxicity Data and Challenges for NCATS-Tested Chemicals Now Available Online
On Dec. 17, 2013, the Environmental Protection Agency (EPA) announced the release of toxicity data available through an interactive Chemical Safety for Sustainability Dashboard. The tool provides user-friendly access to new information about 1,800 chemicals tested by NCATS researchers. The data include information on chemicals commonly used in industrial and consumer products, such as food additives and drugs. This new information can help researchers predict which chemicals may lead to negative health effects.
As part of the release, the agency also announced a series of challenges, inviting the science and technology community to review the data and explore ways to predict the chemicals' health effects. Challenge winners will receive awards for their innovative research ideas.
NCATS played an integral role in developing the toxicity data. Researchers used advanced robotics and high-throughput screening to test each chemical as part of an ongoing federal collaboration called Toxicology in the 21st Century, or Tox21. The program's collaborators, which include NCATS, the National Institute of Environmental Health Sciences, EPA, and the Food and Drug Administration, aim to develop better ways to predict toxic risks to human health.
"Our robotics screening system is an integral part of the Tox21 effort because it provides unparalleled speed, reliability and high-quality reproducible data," said Anton Simeonov, Ph.D., the Tox21 lead at NCATS. "The public release of Tox21 data is sure to accelerate chemical assessment."
Read the EPA news release for details.
NCATS Director Speaks at Partnering for Cures Meeting
Last month, NCATS Director Christopher P. Austin, M.D., spoke at the fifth annual Partnering for Cures meeting as part of a panel discussion. Hosted by FasterCures Nov. 5–8, 2013, in New York, the meeting featured leaders from government, academia, industry and patient advocacy groups. The goal was to encourage collaborations that will speed the process of turning discoveries into treatments.
Austin participated in the panel discussion on "The New Value Proposition for Academic Science," which was moderated by Roxanne Khamsi, Nature Medicine chief news editor. The wide-ranging dialogue touched on value expectations in partnerships between academia, industry and nonprofits; the need for different funding mechanisms to support various types of research; the role academic scientists should play in drug development; and the evolving importance of intellectual property.
Austin described NCATS' role as a "catalyst for collaboration," noting that government can provide a neutral space and act as a "translator" between academia and industry. He explained that NCATS helps bridge the gap between collaborators' differing interests so that they can achieve their primary goal of benefiting patients. Austin also talked about NCATS' work to streamline the translational research process, particularly in the area of toxicology, which is a main reason that clinical trials fail.
"The only way we can solve the toxicology problem is to have a better understanding of how chemicals interact in a systematic way with living systems," he said. "This requires testing large numbers of chemicals, which is the goal of the Tox21 federal collaboration."
Tox21 includes NCATS, the National Institute of Environmental Health Sciences, the Environmental Protection Agency, and the Food and Drug Administration. The program features the kind of systematic knowledge you need to have, Austin added, to really solve the problem and make a difference.
Other panel members included Louis J. DeGennaro, Ph.D., executive vice president and chief mission officer of the Leukemia and Lymphoma Society; Conor Evans, Ph.D., assistant professor at Harvard Medical School; Pearl Huang, Ph.D., vice president and Global Head of Discovery Partnerships in Academia, Alternative Discovery, and Development at GlaxoSmithKline; and Jack Tillman, executive director of Emory Innovations at Emory University. The panelists agreed that translating ideas into treatments requires a multitude of skills and that collaborations are critical and must draw on each partner's unique expertise.
Visit the meeting website to learn more or to watch a video of the full panel discussion.
New BrIDGs Projects Announced to Help Accelerate Therapeutic Development
In December, NCATS officials announced three new projects aimed at advancing treatments for acute radiation syndrome, brain injury from cardiac arrest and a rare disease called beta thalassemia. The projects are supported by the NIH Common Fund's Bridging Interventional Development Gaps (BrIDGs) program, which is led by NCATS.
Through the BrIDGs program, eligible scientists gain access to contractor services, such as toxicology studies, for pre-clinical therapeutic development. To be eligible for the program, projects must have been effective in a disease model. Researchers often apply to BrIDGs because they have hit a roadblock and need additional expertise or lack other resources. Rather than funding successful applicants directly, BrIDGs supports expert NIH contractors who perform pre-clinical services for the researchers free of charge.
"BrIDGs researchers and partner scientists work together to bridge the gap between a basic discovery and clinical testing, thereby ensuring potential treatments have a chance to reach patients who need them," said NCATS Director Christopher P. Austin, M.D.
A primary goal of a BrIDGs project is the submission of an Investigational New Drug application to the Food and Drug Administration to begin human trials.
Read the full news release for details about the new solicitation and new projects, and visit the BrIDGs Projects page for a list of active projects.
Understanding the Brain's Response to Sugar Could Help Treat Obesity
Finding new biomarkers to better prevent, diagnose and treat diseases is one of many translational science challenges that NCATS is working to overcome. Biomarkers, such as cholesterol levels, are biological indicators of the presence, absence or stage of a disease. They can help scientists and clinicians better understand diseases, including obesity, and measure a patient's response to an intervention or treatment.
Although obesity is a growing public health problem, scientists still do not know much about how it develops. Seventy percent of American adults are overweight or obese, and the prevalence of obesity in children is three times higher than it was just a generation ago. Being overweight increases the risk of many other diseases and conditions, including heart disease, Type 2 diabetes, high blood pressure and cholesterol, and stroke. To develop better preventions and treatments, scientists first must understand obesity's causes. Finding biomarkers for the condition could accelerate this process.
Now, a team of researchers from Yale University, supported in part by a Clinical and Translational Science Award from NCATS, have used imaging technology to look at how the brain responds to sugar. This approach could improve scientists' knowledge of the brain's role in obesity and could lead to the development of new biomarkers for the condition. Published in the January 2, 2013, issue of JAMA, the imaging study was a multidisciplinary effort involving experts in endocrinology, psychiatry, basic biology, imaging physics, nursing and biostatistics. Team-based approaches to complex translational science problems are at the heart of all NCATS programs.
Read the full feature.
NCATS Science Featured at 27th NIH Research Festival
Each year, the NIH Research Festival showcases the best in NIH intramural science. The 27th annual event, held Nov. 6–8 at the NIH Clinical Center in Bethesda, Maryland, coincided with the anniversary of both the Clinical Center and the publication of the DNA double-helix structure.
Several NCATS scientists participated as symposium speakers. In a session about "Advances in Natural Product Research," James Inglese, Ph.D., an assay development and screening technology expert in NCATS' Division of Pre-Clinical Innovation (DPI), described how to design assays, or tests, and create screening strategies to explore complex chemical libraries.
RNA interference (RNAi) experts from DPI also participated in the event. Scott Martin, Ph.D., co-chaired a session on "Genes and Pathway Discovery in the Context of Human Disease," and Eugen Buehler, Ph.D., led a talk on recent advances in RNAi screening and its benefits to the research community.
In a session on "The Chemical Biology of Nucleic Acid Synthesis, Modification, and Detection," NCATS' Philip Brooks, Ph.D., program director in the Office of Rare Diseases Research, explained how targeting and delivering nucleic acids could help treat rare genetic diseases.
Others from NCATS highlighted their findings on cancer, genetic and rare diseases, and other topics during poster presentations. Visit the NIH Research Festival website for more information.
Upcoming Events
January
NCATS Advisory Council/Cures Acceleration Network (CAN) Review Board Set to Meet January 16
On Jan. 16, 2014, NCATS will hold a joint meeting of the NCATS Advisory Council and the CAN Review Board on the NIH campus in Bethesda, Maryland. The meeting will feature reports from NCATS Director Christopher P. Austin, M.D., and others about the Center's initiatives, policies, programs and future direction. Information on how to participate can be found on the Events page of the NCATS website. For more information, visit the NCATS Advisory Council page and the CAN Review Board page of the NCATS website.
NCATS in the News
- U.S. EPA Releases Chemical Screening Data on 1,800 Chemicals/Agency Improves Access to Chemical Data and Announces ToxCast Data Challenges • U.S. Environmental Protection Agency • December 17, 2013
- NIH Program Bridges Gap to Develop New Therapeutics • NCATS • December 17, 2013
- siRNAs: Small Molecules that Pack a Big Punch • NIH Director's Blog • December 11, 2013
- Life Tech Teams Up with NIH to Make Gene-Silencing Data Publicly Available • Genetic Engineering & Biotechnology News • December 11, 2013
- Gene-Silencing Data Now Publicly Available to Help Scientists Better Understand Disease • NCATS • December 11, 2013
- Rare Diseases and the Search for a Cure: A Reddit AMA • The Wall Street Journal Health blog • December 9, 2013
- Study Reveals New Targets for Parkinson's Disease • NIH Research Matters • December 9, 2013
- In U.S. First, Stanford Researchers Record Data from Brain of Ambulatory Parkinson's Patient • Stanford School of Medicine • December 5, 2013
- Pamela M. McInnes Named National Center for Advancing Translational Sciences Deputy Director • NCATS • December 3, 2013
- Robots to Cure Rare Diseases: A Reddit Ask Me Anything (AMA) • The Wall Street Journal Health blog • December 3, 2013
- Gene-Silencing Study Finds New Targets for Parkinson's Disease • NCATS • November 24, 2013
- Collaborative Drug Discovery Wins Phase II SBIR Grant to Develop Tools for Biocomputation across Distributed Private Data-sets to Enhance Drug Discovery • Collaborative Drug Discovery, Inc. • November 19, 2013
- Trials: A Desperate Fight to Save Kids & Change Science • The Wall Street Journal • November 14, 2013
- VIDEO: Inside Look at WSJ's 'Trials' Project • The Wall Street Journal • November 14, 2013
- RNA's Secret Life Outside the Cell • Wired Science • November 12, 2013
- VIDEO: This Robot Is Changing How We Cure Diseases • The Wall Street Journal • November 12, 2013
- Human-on-a-Chip • WXXI News • November 6, 2013
- VIDEO: Linking Tiny Organs to Test Drugs • Reuters • November 5, 2013
- Of Mice and Micro-Organs • The New Yorker • November 1, 2013
- NCATS' Dan Tagle Discusses Extracellular RNA in Nature Reviews Drug Discovery • Nature Reviews Drug Discovery • October 31, 2013
Collaborate with NCATS Scientists
NCATS researchers are seeking collaborators in the following areas:
Bridging Interventional Development Gaps (BrIDGs) Program
The BrIDGs program makes available, on a competitive basis, certain critical resources needed for the development of new therapeutic agents. The next opportunity to apply to the BrIDGs program tentatively is scheduled for January/February 2015. Visit the BrIDGs webpage for more information.
NCATS Chemical Genomics Center (NCGC)
NCGC is one of the centers in the Molecular Libraries Probe Production Centers Network (MLPCN), which is an NIH Common Fund initiative. Through the MLPCN, NCGC offers biomedical researchers access to large-scale screening capacity along with the medicinal chemistry and informatics expertise necessary to identify chemical probe molecules and to study the functions of genes, cells and biochemical pathways. For inquiries or to obtain NCGC probe molecules, contact Ajit Jadhav.
NCGC researchers also seek collaborators for assay development and high-throughput screening, chemistry and chemistry technology, automation, and informatics. Learn more.
NIH RNA Interference (RNAi) Initiative
The NIH RNAi initiative, administered by NCATS, provides state-of-the-art, high-throughput RNAi genome-wide screens for humans and mice. This resource is available only to NIH researchers. Scientists interested in performing a high-throughput RNAi screen can contact Scott Martin, Ph.D., for more information.
Toxicology in the 21st Century (Tox21) Program
The Tox21 program aims to test 10,000 chemicals and evaluate their potential to cause health problems. Any investigator may propose the development of biological assays for high-throughput screening.
To suggest an assay, submit an assay nomination form to Menghang Xia, Ph.D. Proposed assays must be compatible with the high-throughput screening guidelines as described in the assay guidance criteria.