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| 28872 | Bias Detection Tools in Health Care Challenge (Old) | Questions?Email NCATS AI Bias Challenge The Minimizing Bias and Maximizing Long-Term Accuracy, Utility and Generalizability of Predictive Algorithms in Health Care Challenge seeks to encourage the development of bias-detection and -correction tools that foster “good algorithmic practice” and mitigate the risk of unwitting bias in clinical decision support algorithms. See more details about the Challenge. WinnersKey DatesBackgroundChallenge GoalsWinnersFirst placeInterFair Project name: InterFair with Fairness Oriented Multiobjective Optimization (FOMO) Members: William La Cava, Elle LettSecond placeMLK Project name: MLK Fairness Members: Amir Asiaee, Kaveh AryanpooAequitas Project name: ESRD Bias Detection and Mitigation Members: Sujatha Subramanian, Jo Stigall, Tenzin Jordan Shawa, Jagadish Mohan, Senthil K. RanganathanThird placeTeam CVP Project name: Debiaser – AI Bias Detection and Mitigation Tool for Clinical Decision Making Members: Manpreet Khural, Wei Chien, Lauren Winstead, Cal ZemelmanSuper2021 Project name: BeFair: A Multi-Level-Reweighing Method to Mitigate Bias Members: Yinghao Zhu, Jingkun An, Enshen Zhou, Hao Li, Haoran FengHonorable MentionDr. Nobias Fünke’s 100% Natural Good-Time Family Bias Solution Project name: Metric Lattice for Performance Estimation (MLPE) Members: Kellen Sandvik, Jesse Rosen, Conor CorbinGenHealth Project name: GenHealth Members: Ricky Sahu, Ethan Siegel, Eric MarriottIcahn School of Medicine Project name: AEquity: A Deep Learning Based Metric for Detecting, Characterizing and Mitigating Dataset Bias Members: Faris F. Gulamali, Ashwin S. Sawant, Jianying Hu, Girish N. NadkarniParaDocs Health Project name: ParaDocs Health Members: Omar Mohtar, Dickson T. Chen, Vibhav Jha, Dhini Nasution, Matt SegarLearn more about the submissions.Key DatesNote: Dates subject to change as necessaryChallenge Announcement: September 1, 2022Registration and Submission Portal Opens: October 31, 2022Submission Deadline: March 1, 2023Technical Evaluation Phase: March 2023Federal Judging Phase: March and April 2023Winners Announced: April 2023Demo Day: May 5, 2023BackgroundAlthough artificial intelligence (AI) and machine learning (ML) algorithms offer promise for clinical decision support (CDS), their potential has yet to be fully realized. Even well-designed AI/ML algorithms and models can become inaccurate or unreliable over time due to various factors, including changes in data distribution; subtle shifts in the data, real-world interactions and user behavior; and shifts in data capture and management practices. Over time, these changes and shifts can degrade the predictive capabilities of algorithms, which can negate the benefits of these types of systems for clinics.How do we detect these shifts or changes on a continual basis to maintain prediction quality? Monitoring an algorithm’s behavior and flagging any significant changes in performance may enable timely adjustments that ensure a model’s predictions remain accurate, fair and unbiased over time. This approach maintains the predictive capability of an algorithm in the real world.As AI/ML algorithms are increasingly used in health care systems, accuracy, generalizability and avoidance of bias and drift become more important. Bias primarily surfaces in two forms. Predictive bias is seen in algorithmic inaccuracies that produce estimates that significantly differ from the underlying truth. Social bias reflects systemic inequities in care delivery leading to suboptimal health outcomes for certain populations.To address these issues and improve clinician and patient trust in AI/ML-based CDS tools, this Challenge invites groups to develop bias-detection and -correction tools that foster “good algorithmic practice” and mitigate the risk of unwitting bias in CDS algorithms.Challenge GoalsThe goal of this Challenge is to identify and minimize inadvertent amplification and perpetuation of systemic biases in AI/ML algorithms used as CDS through the development of predictive and social bias-detection and -correction tools. For this Challenge, participants across academia and the private sector are invited to participate in teams, as representatives of an academic or private entity, or in an individual capacity to design a bias-detection and -correction tool.For most up-to-date information about the rules, submission requirements, judging criteria, prizes, how to enter and to register for the Challenge, please visit the ExpeditionHacks site. You also can visit the Challenge.gov site. | [node:title] | [node:title] | ||||||
| 27577 | Researchers Show How a Tumor Cell’s Location and Environment Affect Its Identity | .caption-right-md { float: right; /* width: 65%; */ width: 50%; margin: 2% 1% 2% 2%; border: 1px solid #ddd; Image shows differences in cell layers’ fluorescent-dye uptake in a model of high-grade serous ovarian cancer. (David B. Morse, Ph.D.)June 23, 2023New approach could provide insights into cancer progression and treatment response, leading to more precise therapies.Using 3-D models of ovarian cancer tumors, scientists found differences in gene activity based on where a cell is in a tumor, demonstrating how a cell’s location and environment in a cancerous tumor can strongly influence which genes are active and the cell’s role in the cancer’s biology. More specifically, the team co-led by researchers at NCATS, part of NIH, showed that gene activity in cells at or near a tumor’s surface differed from that of cells closer to the tumor center.The approach pairs the use of a technology to reveal the genetic activity of single cells within a tumor with fluorescent dyes that spread into tumors. The work could allow researchers to study how the same diseases can vary in people and progress differently. This research could help clinicians identify treatment strategies focused on specific areas in tumors, which could lead to better therapies for cancers and other diseases. The team reported its results June 21 in Cell Systems.“It’s commonly accepted that a cell’s location and surrounding environment influence the cell’s identity,” said Craig Thomas, Ph.D., a translational scientist at NCATS. “Two cells can be genetically identical but have different cellular identities, meaning different genes are turned on because of their location and environment. Our goal was to establish a straightforward method to study this concept in multiple settings.”The new system, called Segmentation by Exogenous Perfusion, or SEEP, takes advantage of a dye that diffuses into cells throughout a tumor at a definable rate. Measuring how much dye gets into individual tumor cells provides information on the cell’s location, and specifically, its access to the outside environment. Using computational methods, the researchers linked this information to cells’ gene activity, allowing the scientists to connect the cells’ identities with their location.“Understanding the relation of cells to each other and the effects of their positions in space has been a fundamental question in cancer, neurological disorders and other areas,” said co-author Tuomas Knowles, Ph.D., at the University of Cambridge.In the work, researchers used three types of 3-D laboratory models – spheroids, organoids and mouse models – created from human ovarian cancer cells. Spheroids are 3-D clusters of cells grown in a lab dish that can mimic some traits of organs and tissues. Organoids, also grown in a dish, are more complex 3-D models that more closely mimic organ and tissue function and structure. In the mouse models, researchers implanted human ovarian cancer cells to form tumors.“It’s critical to understand that not every cell in a tumor will be exposed to a drug in the same way,” Knowles said. “A cancer drug might kill the cells on the surface of a tumor, but the cells in the middle are different and affected differently. That’s likely contributing to why some therapies fail.”The SEEP method revealed that tumor cells near the tumor surface were more likely to undergo cell division than cells closer to the tumor center. Cells on the surface of tumors also turn on genes to protect them from immune system responses. Not surprisingly, these gene responses are linked to how the tumor hides from the body’s immune defenses.Researchers were surprised at the differences in gene activity between cells on or near the surface and those farther inside the ovarian cancer tumor models. The findings could help scientists better understand how tumors are structured. Such information could lead to improved treatments. One possible cancer treatment method could be to target cells likely to be affected in different areas of tumors.“Certain tumor cell types are susceptible to certain therapies,” noted first author and Harvard University medical student David Morse, Ph.D. “Knowing where cells are located and their levels of accessibility in the tumor could help us decide how to use drugs in combination. It could help tell us how long to give a drug and when to move on to other therapies.”The NIH research was supported by NCATS’ Division of Preclinical Innovation and the National Cancer Institute’s Center for Cancer Research. Work at Harvard University was funded by the National Science Foundation (DMR-1708729) and through the Harvard Materials Research Science and Engineering Center (DMR-2011754). The research at Cambridge University was supported by the Biotechnology and Biological Sciences Research Council, the Newman Foundation, the Wellcome Trust, and the European Research Council under the European Union’s Seventh Framework Program (FP7/2007–2013) through the European Research Council grant PhysProt (agreement no. 337969). There also was support by the NIH Oxford–Cambridge Scholars Program and the Certara Biomedical Research Scholarship.Reference: DB Morse, et al. Positional influence on cellular transcriptional identity revealed through spatially segmented single-cell transcriptomics. Cell Systems DOI: https://doi.org/10.1016/j.cels.2023.05.003About NCATS: NCATS conducts and supports research on the science and operation of translation — the process by which interventions to improve health are developed and implemented — to allow more treatments to get to more patients more quickly. For more information about how NCATS helps shorten the journey from scientific observation to clinical intervention, visit https://ncats.nih.gov.About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical and translational medical research, and is investigating the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit https://www.nih.gov.NIH…Turning Discovery Into Health® | [node:title] | [node:title] | ||||||
| 27186 | NIH Gene Therapy Team Reveals Its Path to FDA Orphan Drug and Rare Pediatric Disease Designations | (NCATS)March 29, 2023Platform Vector Gene Therapy project researchers begin to demystify the regulatory process of developing a gene therapy for a rare disease.When NCATS received an Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA), it marked a key accomplishment for researchers in the NIH's Platform Vector Gene Therapy (PaVe-GT) project. NCATS received the ODD for PaVe-GT's AAV9-hPCCA (NCATS-BL0746) investigational gene therapy to treat a form of propionic acidemia, a rare metabolic disorder.“An ODD is a very important development incentive, given the low number of approved products for the thousands of rare diseases,” said Charles Venditti, M.D., Ph.D., a senior investigator at the National Human Genome Research Institute. Venditti is principal investigator for the PaVe-GT propionic acidemia project.An ODD provides financial incentives to make it easier to bring a drug or therapy to market. These incentives include a waiver of the FDA New Drug Application or Biologics License Application, which can cost more than $3 million. Companies receive tax credits and are given seven years to market a drug.NCATS also received a Rare Pediatric Disease (RPD) designation for propionic acidemia. This is a key step in getting a Priority Review Voucher, which can be granted when a drug is approved. The voucher serves as another incentive for rare disease drug development. It can be used to receive a priority review of a later marketing application for a different product. It also can be sold.Launched in 2019, PaVe-GT is building a blueprint for gene therapy development and clinical testing. The goal is to make the process more efficient and easier to access for people with rare diseases. Now, PaVe-GT scientists are starting to share what they have learned in hopes of speeding others' work in this field.“We aim to demystify the gene therapy development process,” said Elizabeth Ottinger, Ph.D., acting director of the NCATS Therapeutic Development Branch. Ottinger leads the preclinical development and regulatory efforts for all four projects within PaVe-GT.In Human Gene Therapy, Venditti, Ottinger and others described what went into the successful ODD and RPD applications. “Applicants must explain why the orphan drug qualifies to receive an ODD. They have to thoroughly describe the U.S. patient population size and experimental data showing potential effectiveness of the new drug or therapy,” Ottinger said. The researchers submitted promising experimental gene therapy data in a novel mouse model with a severe form of propionic acidemia to the FDA.In the Human Gene Therapy article, the team released lightly redacted copies of the ODD and RPD applications. The team also provided templates of the PaVe-GT model for others who are developing gene therapies.“We plan to share the details of our regulatory documentation and experience in PaVe-GT to assist those developing therapeutics for rare diseases,” said NCATS Scientific Project Manager Richa Lomash, Ph.D.Interest in gene therapy for rare diseases has increased in recent years as science and technology have advanced. However, most of the more than 10,000 rare diseases individually affect only a few hundred to a few thousand people. This can make it hard for companies to invest the resources needed to develop and bring a gene therapy for a rare disease to market. The process requires years of research and millions of dollars. Family-led foundations and patient advocacy groups creating research programs for rare diseases can face daunting operational and financial challenges.PaVe-GT scientists plan on using the same gene delivery system and manufacturing methods in multiple rare disease gene therapy clinical trials. They want to see if this approach will allow data to be used across projects. PaVe-GT scientists will share lessons learned and release FDA submissions and related resources publicly. They hope this information will help others navigate the regulatory process. PaVe-GT researchers’ main goal is to get potential treatments to people with rare diseases faster.“PaVe-GT is establishing a viable paradigm for foundations and parent-patient groups for how to get projects over the initial hurdles. This includes the early stages of generating preclinical data needed to move a gene therapy program for rare diseases forward,” Venditti said.“Our progress represents the culmination of efforts from many experts across the NIH,” he said. “It has been informed and supported by patients with propionic acidemia and their families who have participated in our clinical research study. We hope the advances made through PaVe-GT will attract companies to the rare disease space by helping facilitate the path from the lab to the clinic.” | PaVe-GT scientists described their successful applications for two FDA designations for an investigational gene therapy. | NIH gene therapy team details its path to special FDA Designations | PaVe-GT scientists described their successful applications for two FDA designations for an investigational gene therapy. | NIH gene therapy team details its path to special FDA Designations | ||||
| 27135 | As Flights End, Tissue Chips in Space Projects Offer Glimpses Into the Biology of Aging | .caption-right-md { max-width: 350px; } @media only screen and (max-width: 1199px) { .caption-right-md { max-width: 220px; } } International Space Station U.S. National Lab’s Expedition 59 crew member Christina Koch assists with the University of Washington’s and UW Medicine’s kidney tissue chips in space. (NASA)March 23, 2023More than five years into the NCATS-led Tissue Chips in Space program, the final two projects arrived at the International Space Station National Laboratory (ISS National Lab) on March 16, 2023, after a successful launch from the Kennedy Space Center. This is their second and final trip to the ISS National Lab.These final two projects from Stanford University and Johns Hopkins Medicine are examining different aspects of heart function and disease development and the effects of drugs in preventing changes to heart tissue and cells.Tiny Technology, Faster FindingsTissue chips are tiny, bioengineered packages of cells and tissues that can mimic the function of tissues and organs, as well as their environment inside the body. Tissue chips on the ISS National Lab provide a unique opportunity for researchers to model and study conditions related to diseases and aging that mimic what happens to astronauts in the microgravity environment of space. The Tissue Chips in Space projects seek to model these changes — which are like the effects seen in aging — over weeks, rather than the years that it would take for these conditions to occur on Earth.Over the years, nine projects have gone to space. They have studied the aging of the immune system, muscle wasting, injury-related osteoarthritis, age-related changes in kidney function, respiratory system immune defenses, the blood–brain barrier, and the intestines and infection.“The Tissue Chips in Space program showed we could do sophisticated experiments in space and advance translational science,” said Danilo Tagle, Ph.D., director of the NCATS Office of Special Initiatives, which oversees the umbrella Tissue Chip for Drug Screening program. “We’ve pioneered viable long-term science in space, including personalized approaches to therapeutics involving differences in diverse populations’ physiological responses.”The partnership with the National Aeronautics and Space Administration (NASA) and the ISS National Lab was crucial to the program’s success, Tagle said. NASA views tissue chips as a valuable tool for studying astronauts’ physiological responses in space in greater depth.“But more importantly, the lessons learned from these out-of-this-world experiments are geared toward translation of technologies and mitigation of aging effects on Earth,” he said.When the program began in 2017, the initial goal “was just to find out if we could run a tissue chip experiment in low-gravity conditions in space,” Tagle said. Funded researchers needed to show if tissue chips could survive launches, function in microgravity and be able to capture biological markers and hallmarks of the more rapid aging seen in astronauts.Once the initial tissue chips experiments proved possible in space, scientists wanted to identify the molecular changes that caused cells and tissues to mimic the aging process. They tested compounds and drugs to see if they could slow down or prevent aging effects and translate the results into treatments that help people on Earth.The circumstances of spaceflight forced scientists and engineers to innovate. Experiments had to be automated and “astronaut-proof” to lessen the amount of crew time needed to conduct experiments. Engineers had to miniaturize the instrumentation needed to sustain the chips so they fit the payload requirements for both the SpaceX rockets and operations within the ISS National Lab. Scientific teams had to be flexible and deal with changing experiment conditions, challenges in transporting often-fragile cells and tissues, and changing launch schedules.“We had to be creative in how we designed our experiments and be able to adapt and react quickly to problems when they invariably came up,” said Sonja Schrepfer, M.D., Ph.D., a project principal investigator at the University of California, San Francisco.Schrepfer’s team is using tissue chip technology to better understand how a person’s aging immune system can affect how the body heals injured tissue. Her initial experiment was the first NIH-funded tissue chip project to go into orbit.“We can use space and microgravity to induce the immune cells to age rapidly. There’s no other system to do this in,” she explained. “The chips provide a unique opportunity to examine cells in a more human-like physiological environment.”Schrepfer and colleagues think that certain immune cells are tied to the ability of stem cells to regenerate tissue and heal injuries and wounds. Their first space experiments revealed that spaceflight hindered stem cells’ abilities to repair damaged tissue. Since the project’s second flight last year, the scientists have been analyzing the cellular changes. They hope their results will offer opportunities to stop or slow down the aging of immune cells.For Massachusetts Institute of Technology (MIT) biological engineering professor Alan Grodzinsky, Sc.D., low-Earth orbit is a chance to learn more about preventing joint injuries in kids and young adults from developing into osteoarthritis later in life. The MIT tissue chip uses a matrix of human cartilage, bone and the surrounding synovial tissue that creates joint-lubricating fluid to test potential osteoarthritis-preventing treatments.“We want to know what happens years later to the 14-year-old girl who tears her ACL playing soccer,” Grodzinsky said. “When the injury occurs, there’s physical damage and an inflammatory reaction in the knee. It sets the stage for a process that can lead to long-term osteoarthritis. We tried to simulate that process and see if drugs could slow it down.”The Next FrontierThe March 2023 spaceflight will not be the final word from the Tissue Chips in Space program. NCATS plans to issue a funding opportunity aimed at translating what scientists and engineers have learned from the program to improve the use of tissue chips on Earth in terms of automation and miniaturization of the platform instruments.“The goal is to make tissue chip technologies easier to use as turn-key technologies. Companies won’t need to invest in specialized expertise to run platforms,” said Tagle.The Tissue Chips in Space teams will continue to study the results and publish their findings in journals. In the meantime, Tagle and NCATS will work with NASA to test the use of long-term tissue chips. Most of the tissue chip experiments on the ISS National Lab run about a month. They want to see if tissue chips that last as long as six months can help scientists understand what might happen to humans during long spaceflights to Mars. On Earth, researchers hope such tissue chips can model how chronic exposure to radiation, hazardous environments or drugs can affect human health. | The NCATS-led Tissue Chips in Space program sent its final projects to the International Space Station to learn about aging. | As Flights End, Tissue Chips in Space Offers Glimpses into Aging | The NCATS-led Tissue Chips in Space program sent its final projects to the International Space Station to learn about aging. | As Flights End, Tissue Chips in Space Offers Glimpses into Aging | ||||
| 27054 | Scientists Reveal a Potential New Approach to Treating Liver Cancer | NCATS scientists used the center’s drug screening capabilities, including drug screening plates like those shown here, to identify a molecule that was effective in killing liver cancer cells. Researchers determined that a specific enzyme was key to turning the molecule into a potential anticancer drug. (NCATS)March 13, 2023Results in cell and mouse studies may have implications for the development of a new class of anticancer drugs.Scientists at NIH and Massachusetts General Hospital in Boston have uncovered a potential new approach against liver cancer that could lead to the development of a new class of anticancer drugs. In a series of experiments in cells and mice, researchers found that an enzyme produced in liver cancer cells could convert a group of compounds into anticancer drugs, killing cells and reducing disease in animals.The researchers suggest that this enzyme could become a potential target for the development of new drugs against liver cancers, and perhaps other cancers and diseases as well.“We found a molecule that kills cells in a rare liver cancer in a unique way,” said translational scientist Matthew Hall, Ph.D., one of the leaders of the work at NIH’s NCATS. “It emerged from a screening to find molecules that selectively kill human liver cancer cells. It took a lot of work to figure out that the molecule is converted by an enzyme in these liver cancer cells, creating a toxic, anticancer drug.”Hall, Nabeel Bardeesy, Ph.D., a liver cancer specialist at Massachusetts General Hospital and their colleagues reported their results March 13 in Nature Cancer.The finding stems from a collaboration between Massachusetts General Hospital and NCATS researchers. Bardeesy was originally studying cholangiocarcinoma, a type of liver cancer that affects the bile duct. The cancer is characterized by mutations in the IDH1 enzyme. Bardeesy’s team wanted to find compounds and drugs that might be effective against the IDH1 mutation. Through a collaboration with NCATS, Hall and other NCATS scientists rapidly tested thousands of approved drugs and experimental cancer agents for their effectiveness in killing cholangiocarcinoma cells, with IDH1 as a target.They found several molecules, including one called YC-1, could kill the cancer cells. Yet, when they looked to see how YC-1 was working, they discovered the compound wasn’t affecting the IDH1 mutation.The Massachusetts researchers showed that the liver cancer cells made an enzyme, SULT1A1. The enzyme activated the YC-1 compound, making it toxic to tumor cells in cancer cell cultures and mouse models of liver cancers. In the animal models treated with YC-1, the liver tumors either had reduced growth or shrank. Conversely, the researchers found no changes in tumors treated with YC-1 in animals with cancer cells lacking the enzyme.The researchers examined other databases of drug screening results in compound and drug libraries to match drug activity with SULT1A1 activity. They also looked at a large National Cancer Institute database of anticancer compounds for additional possibilities to test for their activity with the enzyme.They identified several classes of compounds that relied on SULT1A1 for their tumor-killing activity. Using computational methods, they predicted other compounds that also likely were dependent on SULT1A1.“Once we found SULT1A1 activated YC-1, it led us to ask, ‘What other compounds are active and can kill cells by the same mechanism?’ Hall said. “Can we identify other compounds that were being developed and demonstrate that they were also active because of SULT1A1 activation? The answer was yes. We found other compounds with the same mechanism of action as YC-1.”The scientists suggest these findings have broader implications for developing new anticancer drugs. “We think these molecules have the potential to be an untapped class of anticancer drugs that depend on SULT1A1 for their activity against tumors,” Bardeesy said.The researchers see YC-1 and similar molecules as prototypes for developing compounds that could be effective against important proteins on cells. Modifying different parts of these molecules could make them more specific for such proteins. The researchers point to the creation of a “toolkit of SULT1A1-activated molecules” that could affect many different targets.Such a toolkit is comprised of hundreds of known molecules. In theory, the toolkit covers many types of enzymes, called sulfotransferases, that are active in different tissues in the body. For example, in addition to SULT1A1, the human sulfotransferase SULT4A1 is active in the brain. It can activate a subset of the molecules in the toolkit. This might be useful in developing drugs specific for brain cancers.“We knew SULT1A1-dependent drugs had already been identified,” Bardeesy said. “Our results suggest there could be other SULT1A1-dependent compounds with ranges of different targets. Identifying such compounds and targets on cells could have potential implications for developing other types of small molecules and drugs, not just limited to these cancers. This might become a new approach for some diseases.”This work was supported by the MGH Fund for Medical Discovery Award; the Cholangiocarcinoma Foundation Christopher J. Wilke Memorial Research Fellowship; NCI 1K99CA245194-01, the V Foundation for Cancer Research, the Department of Defense Translational Team Science Award W81XWH-17-1-0491; NCI SPORE P50 CA127003; the Gallagher Chair in Gastrointestinal Cancer Research and Target Cancer Foundation; and the MGH Excellence Award. Media Contact: NCATS Information Officer, ncatsinfo@mail.nih.gov.About the National Center for Advancing Translational Sciences (NCATS): NCATS conducts and supports research on the science and operation of translation — the process by which interventions to improve health are developed and implemented — to allow more treatments to get to more patients more quickly. For more information about how NCATS helps shorten the journey from scientific observation to clinical intervention, visit https://ncats.nih.gov.About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit https://www.nih.gov.NIH…Turning Discovery Into Health® | A potential new approach against liver cancer could lead to the development of a new class of anticancer drugs. | Scientists Uncover a Potential New Approach to Treating Liver Cancer | A potential new approach against liver cancer could lead to the development of a new class of anticancer drugs. | Scientists Uncover a Potential New Approach to Treating Liver Cancer | ||||
| 26748 | Nurturing the Field of Translational Science | The CTSA Program nurtures the field of translational science through its commitment to education, training and workforce improvement, support for clinical researchers and translational scientists in all fields, and advancement of strong clinical and translational science research. The CTSA Program offers scholars and trainees resources to improve both their own careers and the U.S. biomedical research field. Read about training success stories. July 2019February 2019July 2019CTSA Program Researchers Aim to Improve Health Care from All SidesA research framework that enables the recruitment of hospitalized patients for a wide range of studies can help identify optimal care approaches during and after hospitalization. Undergraduate students play a valuable role in the studies at University of Chicago Medicine, where they recruit patients, conduct follow-up activities, and learn about clinical research.February 2019CTSA Program Supports Emerging Research on Health Effects of PlasticsAn early-career investigator has developed techniques to study how chemicals used in medical devices affect the still-developing hearts of pediatric patients. Program support also enabled her to secure independent funding for larger studies. | The CTSA Program nurtures the field of translational science through its commitment training and workforce development. | Nurturing the Field of Translational Science | The CTSA Program nurtures the field of translational science through its commitment training and workforce development. | Nurturing the Field of Translational Science | ||||
| 26745 | Clinical Research Resources | The CTSA Program creates and applies new scientific discoveries and practical improvements for tools, knowledge and skills, best practices, and resources that make clinical and translational science research higher quality, safer, more efficient, and more effective. Read about clinical research resources success stories. August 2022June 2020August 2022Nationwide IRB Reliance Agreement Aimed at Speeding Research Reaches 1,000 SignatoriesThe Streamlined, Multisite, Accelerated Resources for Trials (SMART) Institutional Review Board (IRB) agreement has reached 1,000 participating sites, making it one of the largest medical research study reliance agreements in the United States.June 2020Teaching Children About Translational Science and Clinical TrialsCTSA Program researchers from the University at Buffalo created “Sofia Learns About Research,” a coloring and activity book that introduces children and their guardians to translational science and teaches them about the importance of clinical trials. | The CTSA Program creates and applies resources that make research higher quality, safer, and more effective. | Clinical Research Resources | The CTSA Program creates and applies resources that make research higher quality, safer, and more effective. | Clinical Research Resources | ||||
| 26742 | Developing, Demonstrating and Disseminating Innovations That Turn Science into Medicine Faster | The CTSA Program’s network shows that new scientific discoveries and logistic innovations can speed up translational research projects of all sizes. The program is supported by partnerships with research centers and communities which help provide the benefits of translational science to all people more quickly. Read about success stories in turning science into medicine faster.December 2023March 2023February 2023October 2021September 2021March 2021January 2021January 2020October 2019August 2019June 2019January 2019December 2023GEMINI Study Reveals Advantages for Whole Genome Sequencing in Infants GEMINI researchers, supported by the CTSA Program, compared two approaches to genetic testing in infants. The results of the study could help doctors choose the right testing options for their patients.March 2023Collaboration Opens Door to Potential Therapies for Children With a Rare Disease Clinicians historically have focused on treating the symptoms of a rare lung disease called primary ciliary dyskinesia (PCD). A recent study using medical images from children with PCD could help point to new therapeutic candidates for slowing damaging effects linked with the disease. It also can help diagnose this disease sooner. The study was a collaboration among researchers funded through the Genetic Disorders of Mucociliary Clearance Consortium within the Rare Diseases Clinical Research Network (RDCRN) and the Colorado Clinical and Translational Sciences Institute.February 2023Community Engagement Approach Targets Louisville’s Colorectal Cancer Disparities An innovative study conducted in partnership with Black churches highlights the need for additional outreach and education to reduce colorectal cancer screening disparities in Black communities. Researchers will apply lessons learned to develop community-based interventions that target disparities in an upcoming study.October 2021Genetic Analysis Suggests Dilated Cardiomyopathy Therapies May Work for Rare Peripartum Cardiomyopathy Analyzing genetic information drawn from patients and multiple databases, CTSA Program researchers discovered similarities between nonischemic dilated cardiomyopathy and peripartum cardiomyopathy.September 2021National EHR Data Resource Reveals COVID-19’s Stark Mortality Risk in People with COPD Northwestern University researchers using data from the National COVID Cohort Collaborative Data Enclave found that individuals with COPD were more likely to be hospitalized and die of COVID-19 than those without COPD.March 2021Low Vitamin D Levels May Boost COVID-19 Risk in Black People CTSA Program researchers find a link between low vitamin D levels and a higher risk of testing positive for COVID-19 in Black people.January 2021CTSA Program-Supported Researchers May Turn Brown Fat into an Ally Against Obesity CTSA Program researchers discover how brown fat may help reduce the risk of heart disease, type 2 diabetes and other cardiometabolic diseases, particularly in people who are obese.January 2020NCATS Funds Network to Improve the Use of Telehealth in Children’s Health Care CTSA Program-supported researchers are harnessing their resources and expertise to evaluate access to high-quality telehealth care for rural and underserved children.October 2019Ketogenic Diet May Offer a New Approach to Treating Alzheimer’s Disease CTSA Program-supported researchers tested the hypothesis that ketones could serve as a source of energy for the brain in people with Alzheimer’s disease (AD). The study found improved brain function in those with mild AD after a three-month ketogenic diet.August 2019NCATS-Supported Research Reduces Time to Diagnosis for Seriously Ill Children with Genetic Diseases NCATS-supported researchers have developed an automated approach to diagnosis of genetic diseases in seriously ill children to allow faster diagnosis and initiation of treatment, and, ultimately, better outcomes. The study appeared in the April 24, 2019, issue of Science Translational Medicine.June 2019CTSA Program Support Enables Development of Life-Saving Blood Loss Monitor NCATS-supported researchers used applied machine-learning to develop an innovative device that detects internal bleeding and monitors a patient’s response to blood loss. The monitor helps medical staff identify appropriate treatment before a patient goes into life-threatening shock. The device was approved by the U.S. Food and Drug Administration in 2018 and is in clinical use today.January 2019NCATS-Supported Researchers Find Exercise May Help Protect DNA CTSA Program-supported researchers who studied older caregivers found that those who exercised had longer telomeres (the caps that protect the ends of DNA). These findings may lead to better health outcomes for older adults as they age. | The CTSA Program’s network shows that discoveries and operational innovations can speed translational research projects. | Turning Science into Medicine Faster | The CTSA Program’s network shows that discoveries and operational innovations can speed translational research projects. | Turning Science into Medicine Faster | ||||
| 26739 | Urgent Public Health Needs | The CTSA Program’s unique network of leading research centers helps the program respond quickly to urgent public health needs. The network works to swiftly increase scientific knowledge and turn it into health solutions for problems ranging from the opioid epidemic to infectious diseases, such as the COVID-19 pandemic. Read about success stories in addressing urgent public health needs.November 2023September 2023March 2023February 2023September 2022June 2022May 2022January 2022April 2021October 2020September 2020June 2020March 2019November 2023COVID-19 Didn’t Drive Worse Outcomes for Babies in Neonatal Intensive Care UnitsBabies admitted to neonatal intensive care units (NICUs) during the first 21 months of the COVID-19 pandemic were unlikely to be diagnosed with COVID-19. Moreover, those who were COVID positive did not experience higher rates of harmful effects and mortality than those without COVID-19. This is according to CTSA Program–supported researchers who studied data from more than 150,000 infants discharged from NICUs between January 2020 and September 2021.September 2023Metformin Shows Promise in Treating COVID-19 and Preventing Long-COVID With support from CTSA Program institutions, NCATS is exploring metformin as a treatment for COVID-19 — from early observational studies all the way to large-scale clinical trials. Now, the ACTIV-6 clinical trial is testing the drug as an outpatient treatment for people with mild-to-moderate COVID-19 to bring clarity to its value in treating COVID-19 and potentially preventing long COVID.March 2023Rural Hospital Closures Put a Strain on Nearby Hospitals, Potentially Jeopardizing Access to Health Care in Rural Communities CTSA Program–supported research reveals that rural hospital closures nationwide strain the ability of surrounding hospitals to care for the increase in patients. This ripple effect jeopardizes rural communities’ access to health care.February 2023Research Reveals Nationwide Spread of Potentially Life-Threatening Fungal Infections CTSA Program–supported research found that three fungal infections spread outside their usual regions and now appear in at least half of the United States. These findings could speed recognition and treatment outside typical areas of infection.September 2022Previous Common Colds Could Boost Risks of More Severe COVID-19 Having a common cold caused by seasonal coronaviruses may cause immune distraction, making some people’s immune systems respond less effectively to SARS-CoV-2 infection and increase their risk of more severe COVID-19.N3C Data Reveal More Severe COVID-19 Outcomes in Rural Communities After examining patient health records from the National COVID Cohort Collaborative, researchers found that people with COVID-19 who live in rural areas are more likely to be hospitalized than those who live in urban areas.June 2022Study Finds Immune Dysfunction Is a Significant Risk Factor for COVID-19 Breakthrough Infection The National COVID Cohort Collaborative Data Enclave helps researchers identify a link between COVID-19 breakthrough infections and people with abnormal or impaired immune systems.May 2022Scientists Identify Characteristics to Better Define Long COVID NIH-supported researchers analyzed an unprecedented collection of electronic health records in NCATS’ National COVID Cohort Collaborative Data Enclave to better identify common features of long COVID. Researchers Use Cutting-Edge EHR Data Resource to Find Risk Factors for Severe COVID-19 in Children Researchers used data from NCATS’ National COVID Cohort Collaborative Data Enclave to discover why some children with COVID-19 developed a dangerous condition called multisystem inflammatory syndrome in children, also known as MIS-C.January 2022International Registry Reveals Risks COVID-19 Poses with Sickle Cell Disease NCATS-funded CTSA Program researchers developed a collaborative registry that collects data on COVID-19 illness in people with sickle cell disease.April 2021Large Clinical Trial to Study Repurposed Drugs to Treat COVID-19 Symptoms The trial will test several existing drugs to see if they can provide safe, effective symptom relief and prevent hospitalization in people with mild to moderate COVID‑19. Two CTSA Program hubs served as coordinating centers and partner with the Patient-Centered Outcomes Research Institute to expedite enrollment.October 2020NIH Begins Large Clinical Trial to Test Immune Modulators for Treatment of COVID-19 The CTSA Program played a key role in rapidly implementing a clinical trial to evaluate the safety and efficacy of immune modulator drugs in hospitalized adults with COVID-19. September 2020NIH Expands Clinical Trials to Test Convalescent Plasma Against COVID-19 Two randomized, placebo-controlled clinical trials funded by NIH are expanding enrollment to further evaluate convalescent plasma as a treatment for people hospitalized with COVID-19. The CTSA Program research network, including its Trial Innovation Network, played a key role in rapidly expanding enrollment in the trials.June 2020NIH Launches Analytics Platform to Harness Nationwide COVID-19 Patient Data to Speed Treatments NIH launched a centralized, secure enclave to store and study vast amounts of medical record data from people diagnosed with coronavirus disease across the country. It is part of an effort, called the National COVID Cohort Collaborative, to help scientists analyze these data to understand the disease and develop treatments.March 2019Opioids Increase the Risk of Pneumonia Research, supported in part by the CTSA Program, suggests that opioids can increase a person’s risk for pneumonia that is severe enough to warrant hospitalization. | The CTSA Program’s network of leading research institutions helps the program respond quickly to urgent public health needs. | Urgent Public Health Needs | The CTSA Program’s network of leading research institutions helps the program respond quickly to urgent public health needs. | Urgent Public Health Needs | ||||
| 26553 | New 3-D Model Offers Insights into the Role of Glucose in a Deadly Kidney Disease | Mini kidney tube structures have sugar receptors (red, upper left) and form outward-facing polycystic kidney disease cysts (center image), which swell by taking in sugar (green, lower right). (University of Washington)January 5, 2023Combining organ-in-a-dish and organ-on-a-chip technologies could lead to ways to test drugs and develop therapies for a common genetic disorder.A research team supported by NIH has developed a new approach to better understand the biology of polycystic kidney disease (PKD), an often-life-threatening genetic disorder that affects millions worldwide. Scientists combined two ways to model the disorder — organ-in-a-dish and organ-on-a-chip technologies — to show the role of glucose, a sugar commonly found in blood, in forming PKD cysts. The results, reported in Nature Communications, could lead to better ways to test and develop treatments for PKD, and perhaps other diseases.An organ-in-a-dish, or organoid, is a miniature version of an organ grown in a laboratory dish. It can mimic key features of a human organ’s structure and function. Organs-on-a-chip, or tissue chips, are more complex 3-D models, containing channels and living cells, that aim to mimic organ and tissue structure and environment. NIH’s NCATS research programs develop both technologies as human cell–based approaches to study disease and better predict whether drugs will be safe or toxic in humans.In PKD, tiny tubes (tubules) in the kidneys expand like water balloons, forming sacs of fluid over decades. The sacs, or cysts, eventually crowd out healthy tissue, leading to problems in kidney function and kidney failure. Scientists have identified many of the genes that cause PKD, but much about the disease remains unknown, including how the cysts form.“We’re able to boil down a complex process of cyst formation in tubules into a process in a petri dish that takes just a few weeks, but there’s been a lack of technologies to study the disease further,” said University of Washington School of Medicine scientist Benjamin Freedman, Ph.D., who led the work. “Animal models are helpful, but translating the results of those studies to people has been a challenge.”Freedman, co-author Jonathan Himmelfarb, M.D., and their Seattle-based colleagues decided to explore combining organoid technology with a tissue-chip platform. Scientists believe that fluid flow is important in the development of cysts, but they had no way of testing the theory in organoids.“In kidneys, fluid is always going through the tubules; at any given moment the kidneys have about 25% of the body fluid going through them,” Freedman explained. “We can’t reproduce this system in the dish because fluid needs to move through the kidney structures. Using microfluidic technology in tissue chips was a natural next step.”Freedman’s group showed that exposing the PKD organoid-on-a-chip model to a combination of water, sugar, amino acids and other nutrients caused cysts to expand relatively quickly. They found that the cysts were absorbing glucose and pulling in water from the fluid passing over them, making the cysts grow larger. Although glucose is generally absorbed by the kidneys, glucose absorption has not been connected to cyst formation in PKD.“It wasn’t a huge surprise that the cysts could absorb glucose, but it was surprising that they were dependent on it. It’s a new way of thinking of how these cysts form,” Freedman said.The scientists added fluorescent glucose to mice with PKD and found that the mouse cysts also took up the glucose. “We think the tubules are taking in fluid in the mice, just like in the organoids. The kidney gets bigger, and as the tubules widen to accommodate the expansion over time, cysts form,” Freedman said.Understanding the mechanisms of PKD can point to new ways to treat it. As part of the study, the research team showed that adding compounds that block glucose transport prevented cyst growth. Freedman noted glucose inhibitors are being developed for other types of kidney disease.“The researchers have shown that simulating fluid flow is essential to making this system more like the environment in the kidney with PKD,” said Danilo Tagle, Ph.D., director of the NCATS Office of Special Initiatives. “Combining the two technologies makes tissue chip technology more adaptable to drug discovery and drug development and allows researchers to take advantage of the strengths of both platforms. This is very promising for studying other diseases in new ways in the future.”The research was supported by NCATS; the National Institute of Diabetes and Digestive and Kidney Diseases; and the National Heart, Lung, and Blood Institute through NIH grants UG3TR002158, UG3TR003288, UG3TR000504, K01DK102826, R01DK117914, U01DK127553, UC2DK126006, and U01HL152401. Media Contact: NCATS Information Officer, ncatsinfo@mail.nih.gov.About the National Center for Advancing Translational Sciences (NCATS): NCATS conducts and supports research on the science and operation of translation — the process by which interventions to improve health are developed and implemented — to allow more treatments to get to more patients more quickly. For more information about how NCATS helps shorten the journey from scientific observation to clinical intervention, visit https://ncats.nih.gov.About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit https://www.nih.gov.NIH…Turning Discovery Into Health® | NIH-supported scientists developed an approach using organoids to better understand the biology of polycystic kidney disease. | /sites/default/files/Tissue_Chips_U_of_Washington_PKD_900x600_0.jpg | 3-D Model Offers Insights into the Role of Glucose in Kidney Disease | NIH-supported scientists developed an approach using organoids to better understand the biology of polycystic kidney disease. | /sites/default/files/Tissue_Chips_U_of_Washington_PKD_900x600_1.jpg | 3-D Model Offers Insights into the Role of Glucose in Kidney Disease |
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