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  • UMass Amherst Researcher Wins $3 Million ‘Outstanding New Environmental Scientist’ Award

    UMass Amherst Researcher Wins $3 Million ‘Outstanding New Environmental Scientist’ Award

    A University of Massachusetts Amherst epidemiologist has received a five-year, $3 million Outstanding New Environmental Scientist (ONES) grant from the National Institute of Environmental Health Sciences (NIEHS) in his ongoing effort to discover more about the origins and risk factors of autism. 

    The highly competitive NIEHS program, awarded just once a year to only a handful of young scientists, is designed to support innovative environmental health research by cultivating research leaders in the field early in their careers.  

    Image

    Youssef Oulhote

    UMass Amherst assistant professor Youssef Oulhote

    Youssef Oulhote, assistant professor in the School of Public Health and Health Sciences, will probe the interplay of early life exposure to environmental pollutants, the folate system during pregnancy and genetic susceptibility in the onset of autistic behaviors. 

    “We have multiple parts of the puzzle,” Oulhote says. “We want to put them together and add things that we don’t know yet.” 

    Oulhote will lead the project in collaboration with School of Public Health and Health Sciences colleagues Raji Balasubramanian, professor of biostatistics, and Anna Maria Siega-Riz, professor and dean. The research team also includes collaborators from Baylor College of Medicine, Brown University, Simon Fraser University in British Columbia, Canada, and Health Canada. 

    “This is a very prestigious award for Dr. Oulhote, reflecting the important contribution this research will make to the scientific field and his potential for being a leader in this field,” Siega-Riz says. “I am delighted to offer my expertise in nutritional epidemiology and am looking forward to working with him and the other investigators on this very important public health topic.” 

    To investigate several modifiable risk factors of autism in a comprehensive manner, Oulhote and colleagues will turn again to data from the Maternal-Infant Research on Environmental Chemicals (MIREC) prospective cohort study. MIREC enrolled 2,001 women during their first trimester of pregnancy from 10 cities in Canada between 2008 and 2011. The study already has resulted in more than 70 papers in scientific journals, including two led by Oulhote in Environmental Health Perspectives and Environment International. 

    Oulhote’s new research will build on the findings that exposure in the womb to phthalates – endocrine-disrupting chemicals found in common household products – was associated with autistic traits in young boys. But this link was not apparent in children whose mothers had taken the recommended dose of folic acid during the first trimester of their pregnancy.  

    “We want to look at other chemicals like air pollutants, especially ultra-fine particles, and pesticides, and also the constituents of those particles,” Oulhote says. 

    The research team will measure phthalates and organophosphate pesticides across two trimesters of pregnancy and estimate monthly exposures to individual air pollutants, such as nitrogen dioxide and particulate matter and its composition, across pregnancy and during the child’s first year.  

    They will also look at folate levels in maternal blood samples, as well as folate receptor autoantibodies. “It appears that the mothers of kids with autism have a higher prevalence of folate receptor autoantibodies that interfere with folate metabolism and transport. So even if they have enough folate intake, it may not be transported properly to the brain,” Oulhote explains.  

    The use of sophisticated statistical models will help researchers understand the intricacies and interplay and impact of various risk factors. “We’re applying and adapting newly developed machine learning methods because we know we have a complex problem,” Oulhote says. “You can’t just look at everything separately – we want to take a holistic view and have methods that can take into account this complexity.” 

    Oulhote hopes the research will lead to better prevention strategies for autism spectrum disorder and its associated behaviors at both the individual and population levels.  

    “We want to gain a better understanding of how strongly multiple pollutants and the folate system are associated with autistic traits, whether these chemicals are associated with circulating folate concentrations, and how these effects of multiple pollutants differ based on folic acid intake, genetic susceptibility and the presence folate autoantibodies,” he says.  

  • Eight Substances Added to 15th Report on Carcinogens

    Eight Substances Added to 15th Report on Carcinogens

    Eight substances have been added to the Report on Carcinogens, bringing the total list to 256 substances that are known, or reasonably anticipated, to cause cancer in humans. This is the 15th Report on Carcinogens, which is a cumulative report, mandated by Congress and prepared by the National Toxicology Program (NTP) for the Secretary of the U.S. Department of Health and Human Services. The release of this report coincides with the 50th Anniversary of the National Cancer Act of 1971, which initiated the nation’s war on cancer.

    In the new report, chronic infection with the bacterium Helicobacter pylori (H. pylori) is listed as known to be a human carcinogen. The flame-retardant chemical antimony trioxide, and six haloacetic acids (HAAs) found as water disinfection byproducts are listed as reasonably anticipated to be a human carcinogen.

    “Cancer affects almost everyone’s life, either directly or indirectly,” said Rick Woychik, Ph.D., director of the National Institute of Environmental Health Sciences and NTP. “As the identification of carcinogens is a key step in cancer prevention, publication of the report represents an important government activity towards improving public health.”

    The Report on Carcinogens identifies many different environmental factors, collectively called substances, including chemicals; infectious agents, such as viruses; physical agents, such as X-rays and ultraviolet radiation; and exposure scenarios. A substance is listed as either known to be a human carcinogen or reasonably anticipated to be a human carcinogen, to indicate the potential hazard.

    The report does not include estimates of cancer risk because many factors affect whether a person will or will not develop cancer. Those include the carcinogenic potency of the substance, the level and duration of exposure, and an individual’s susceptibility to the carcinogenic action of the substance.

    Chronic Infection With H. pylori

    H. pylori is a bacterium that colonizes in the stomach and can cause gastritis and peptic ulcers. Most people do not show symptoms. Chronic infection may lead to stomach cancer and a rare type of stomach lymphoma. Infection primarily occurs from person-to-person contact, especially in crowded housing conditions, and may occur by drinking well water contaminated with H. pylori.

    People living in poverty and certain racial, ethnic, and immigrant groups are disproportionately affected by H. pylori infection. Treatment of infected people who have stomach ulcers or signs of stomach infection can decrease their risk of cancer.

    Antimony Trioxide

    Antimony trioxide is primarily used as a component of flame-retardants in plastics, textiles, and other consumer products. Highest exposure occurs among workers who produce the substance or use it to make flame retardants.

    Other people are potentially exposed to low levels of antimony trioxide from breathing contaminated outdoor air or dust from the wear and tear of flame-retardant-treated consumer products, such as carpets and furniture. State and federal agencies limit exposure to the substance in the workplace and the environment through regulation.

    Six Haloacetic Acids (HAAs) Found As Water Disinfection Byproducts

    Water treatment removes contaminants and disease-causing agents from drinking water. HAAs are formed during the disinfection of water from a reaction between the chlorine-based disinfection agents and organic matter in the source water.

    Approximately 250 million U.S. residents use community water systems and are potentially exposed to HAAs in disinfected water. Municipal water systems monitor for some HAAs. Improvements in disinfection technology, such as filtration methods, can reduce the levels of HAAs in drinking water.

    The following six HAAs are included in the report:

    • Bromochloroacetic acid (BCA)
    • Bromodichloroacetic acid (BDCA)
    • Chlorodibromoacetic acid (CDBA)
    • Dibromoacetic acid (DBA)
    • Dichloroacetic acid (DCA)
    • Tribromoacetic acid (TBA)

    About the National Toxicology Program (NTP): NTP is a federal, interagency program headquartered at NIEHS, whose goal is to safeguard the public by identifying substances in the environment that may affect human health. For more information about NTP and its programs, visit ntp.niehs.nih.gov.

  • Chronic Exposure to Air Pollution May Increase Risks for ICU Admission or Death Among COVID-19 Patients, Study Finds

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    Reference #18.19593a17.1791980565.43d60c9

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  • Researchers Target a Mouse’s Own Cells, Rather Than Using Antibiotics, to Treat Pneumonia

    Researchers Target a Mouse’s Own Cells, Rather Than Using Antibiotics, to Treat Pneumonia

    Researchers at the National Institutes of Health have discovered a therapy that targets host cells rather than bacterial cells in treating bacterial pneumonia in rodents. The method involves white blood cells of the immune system called macrophages that eat bacteria, and a group of compounds that are naturally produced in mice and humans called epoxyeicosatrienoic acids or EETs. The research was published in the Journal of Clinical Investigation.

    According to the World Health Organization, pneumonia caused by Streptococcus pneumoniae, or pneumococcal pneumonia, is the leading cause of pneumonia deaths worldwide each year. While physicians usually prescribe antibiotics to treat this severe lung infection, treatment is not always successful, and in some cases, the bacteria become resistant.

    Matthew Edin, Ph.D., a scientist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, wanted to find a way to augment the body’s immune system to resolve the infection.

    To keep tissues healthy, EETs work to limit inflammation, but during infections caused by S. pneumoniae and other microorganisms, inflammation ramps up after lung cells induce certain substances that prompt macrophages to gobble up the bacteria. Edin and colleagues found that one way to get macrophages to eat more bacteria is to decrease the ability of EETs to do what they normally do, which is limit inflammation.

    Edin led the team that found infection induces a protein called soluble epoxide hydrolase (sEH) that degrades EETs. In contrast, when sEH is blocked, EET levels skyrocket, hampering the macrophages’ ability to sense and eat bacteria. As a result, the bacteria continue to reproduce in the lung, which leads to severe lung infection and death.

    At the other end of the spectrum, blocking EETs using a synthetic molecule called EEZE boosted the eating capacity of the macrophages, leading to reduced numbers of bacteria in the lungs of mice. The scientists saw the same result when they placed bacteria and macrophages harvested from lung and blood samples of human volunteers in test tubes at the NIEHS Clinical Research Unit.

    “EEZE is safe and effective in mice, but scientists could develop similar compounds to give to humans,” said Edin, who is co-lead author of the paper. “These new molecules could be used in an inhaler or pill to promote bacterial killing and make the antibiotics more effective.”

    NIEHS Scientific Director Darryl Zeldin, M.D., corresponding author of the research, has spent several years studying EETs and their impact on the human body. He and his research group determined that EETs provide beneficial cardiovascular effects, such as lowering blood pressure and inflammation, and improving cell survival after a stroke or heart attack. He stressed, however, that the involvement of EETs in the process of inflammation can be good or bad depending on the context.

    “EETs can suppress the inflammatory response, which is good, but if they block it too much, they’re going to make it so the macrophages can’t eat the bacteria, which is bad,” said Zeldin.

    Edin added that some researchers have tested sEH inhibitors — compounds that prevent sEH from degrading EETs — in clinical trials to see if they could help with pain, chronic obstructive pulmonary disease, and high blood pressure. He cautioned that the scientists performing these studies consider the influence of sEH inhibitors on bacterial clearance.

    “They should be careful and stop using them if the individual develops pneumonia,” said Edin. “Our study demonstrated that blocking sEH means EETs may hamstring macrophages, making a lung infection worse.”

    Co-author Stavros Garantziotis, M.D., medical director of the NIEHS Clinical Research Unit, was instrumental in collecting human macrophages for the research.

    “Since our study utilized lung immune cells from healthy volunteers, we have confidence that our findings are relevant to human health,” said Garantziotis.

    Grant Number: Z01ES025034

    Reference: Li H, Bradbury JA, Edin ML, Graves JP, Gruzdev A, Cheng J, Hoopes SL, DeGraff LM, Fessler MB, Garantziotis S, Schurman SH, Zeldin DC. 2021. sEH promotes macrophage phagocytosis and lung clearance of Streptococcus pneumoniae. J Clin Invest: doi: 10.1172/JCI129679 [Online 30 September 2021]. [Abstract Li H, Bradbury JA, Edin ML, Graves JP, Gruzdev A, Cheng J, Hoopes SL, DeGraff LM, Fessler MB, Garantziotis S, Schurman SH, Zeldin DC. 2021. sEH promotes macrophage phagocytosis and lung clearance of Streptococcus pneumoniae. J Clin Invest: doi: 10.1172/JCI129679 [Online 30 September 2021].]


  • NIH Awards Nearly $75m to Catalyze Data Science Research in Africa

    NIH Awards Nearly $75m to Catalyze Data Science Research in Africa

    Tuesday, October 26, 2021

    NIH awards nearly $75M to catalyze data science research in Africa

    Data scientists at work.

    BBC

    The National Institutes of Health is investing about $74.5 million over five years to advance data science, catalyze innovation and spur health discoveries across Africa. Under its new Harnessing Data Science for Health Discovery and Innovation in Africa (DS-I Africa) program, the NIH is issuing 19 awards to support research and training activities. DS-I Africa is an NIH Common Fund program that is supported by the Office of the Director and 11 NIH Institutes, Centers and Offices.

    Awards will establish a consortium consisting of a data science platform and coordinating center, seven research hubs, seven data science research training programs and four projects focused on studying the ethical, legal and social implications of data science research. Awardees have a robust network of partnerships across the African continent and in the United States, including numerous national health ministries, nongovernmental organizations, corporations, and other academic institutions.

    “This initiative has generated tremendous enthusiasm in all sectors of Africa’s biomedical research community,” said NIH Director Francis S. Collins, M.D., Ph.D. “Big data and artificial intelligence have the potential to transform the conduct of research across the continent, while investing in research training will help to support Africa’s future data science leaders and ensure sustainable progress in this promising field.”

    The University of Cape Town (UCT) will develop and manage the initiative’s open data science platform and coordinating center, building on previous NIH investments in UCT’s data and informatics capabilities made through the Human Heredity and Health in Africa (H3Africa) program. UCT will provide a flexible, scalable platform for the DS-I Africa researchers, so they can find and access data, select tools and workflows, and run analyses through collaborative workspaces. UCT will also administer and support core resources, as well as coordinate consortium activities.

    The research hubs, all of which are led by African institutions, will apply novel approaches to data analysis and AI to address critical health issues including:

    • Scientists in Kenya will leverage large, existing data sets to develop and validate AI models to identify women at risk for poor pregnancy outcomes; and to identify adolescents and young healthcare workers at risk of depression and suicide ideation.
    • A hub in Nigeria will study SARS-CoV-2 and HIV with the goal of using data to improve pandemic preparedness.
    • In Uganda, researchers will advance data science for medical imaging with efforts to improve diagnoses of eye disease and cervical cancer.
    • Scientists in Nigeria will also study anti-microbial resistance and the dynamics of disease transmission, develop a portable screening tool for bacterial infections and test a potential anti-microbial compound.
    • A project based in Cameroon will investigate ways to decrease the burden of injuries and surgical diseases, as well as improve access to quality surgical care across the continent.
    • From a hub in South Africa, researchers will study multi-disease morbidity by analyzing clinical and genomic data with the goal of providing actionable insights to reduce disease burden and improve overall health.
    • A project in South Africa will develop innovative solutions to mitigate the health impacts of climate change throughout the region, with initial studies of clinical outcomes of heat exposure on pregnant women, newborns and people living in urban areas.

    The research training programs, which leverage partnerships with U.S. institutions, will create multi-tiered curricula to build skills in foundational health data science, with options ranging from master’s and doctoral degree tracks, to postdoctoral training and faculty development. A mix of in-person and remote training will be offered to build skills in multi-disciplinary topics such as applied mathematics, biostatistics, epidemiology, clinical informatics, analytics, computational omics, biomedical imaging, machine intelligence, computational paradigms, computer science and engineering. Trainees will receive intensive mentoring and participate in practical internships to learn how to apply data science concepts to medical and public health areas including the social determinants of health, climate change, food systems, infectious diseases, noncommunicable diseases, health surveillance, injuries, pediatrics and parasitology.

    Recognizing that data science research may uncover potential ethical, legal and social implications (ELSI), the consortium will include dedicated ELSI research addressing these topics. This will include efforts to develop evidence-based, context specific guidance for the conduct and governance of data science initiatives; evaluate current legal instruments and guidelines to develop new and innovative governance frameworks to support data science health research in Africa; explore legal differences across regions of the continent in the use of data science for health discovery and innovation; and investigate public perceptions and attitudes regarding the use of data science approaches for healthcare along with the roles and responsibilities of different stakeholder groups regarding intellectual property, patents, and commercial use of genomics data in health. In addition, the ELSI research teams will be embedded in the research hubs to provide important and timely guidance.

    A second phase of the program is being planned to encourage more researchers to join the consortium, foster the formation of new partnerships and address additional capacity building needs. Through the combined efforts of all its initiatives, DS-I Africa is intended to use data science to develop solutions to the continent’s most pressing public health problems through a robust ecosystem of new partners from academic, government and private sectors.

    In addition to the Common Fund (CF), the DS-I Africa awards are being supported by the Fogarty International Center (FIC), the National Cancer Institute (NCI), the National Human Genome Research Institute (NHGRI), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute of Environmental Health Sciences (NIEHS), the National Institute of Mental Health (NIMH), the National Library of Medicine (NLM) and the NIH Office of Data Science Strategy (ODSS). The initiative is being led by the CF, FIC, NIBIB, NIMH and NLM.  

    More information is available at https://commonfund.nih.gov/AfricaData.

    Photos depicting data science activities at awardee institutions are available for downloading at https://commonfund.nih.gov/africadata/images. 

    About the NIH Common Fund: The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs. Common Fund programs are managed by the Office of Strategic Coordination in the Division of Program Coordination, Planning, and Strategic Initiatives in the NIH Office of the Director in partnership with the NIH Institutes, Centers, and Offices. More information is available at the Common Fund website: https://commonfund.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 www.nih.gov.

    NIH…Turning Discovery Into Health®

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  • Balbus Elected to National Academy of Medicine

    Balbus Elected to National Academy of Medicine

    The National Academy of Medicine (NAM) today announced the election of 90 regular members and 10 international members during its annual meeting. Election to the Academy is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service. 

    “It is my honor to welcome this truly exceptional class of new members to the National Academy of Medicine,” said NAM President Victor J. Dzau. “Their contributions to health and medicine are unparalleled, and their leadership and expertise will be essential to helping the NAM tackle today’s urgent health challenges, inform the future of health care, and ensure health equity for the benefit of all around the globe.” 

    New members are elected by current members through a process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care, and public health. A diversity of talent among NAM’s membership is assured by its Articles of Organization, which stipulate that at least one-quarter of the membership is selected from fields outside the health professions — for example, from such fields as law, engineering, social sciences, and the humanities. The newly elected members bring NAM’s total membership to more than 2,400, which includes 198 international members. 

    Established originally as the Institute of Medicine in 1970 by the National Academy of Sciences, the National Academy of Medicine addresses critical issues in health, science, medicine, and related policy and inspires positive actions across sectors. NAM works alongside the National Academy of Sciences and National Academy of Engineering to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies of Sciences, Engineering, and Medicine also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding of STEMM. With their election, NAM members make a commitment to volunteer their service in National Academies activities.

    Newly elected regular members of the National Academy of Medicine and their election citations are:

    Daniel G. Anderson, PhD, professor, department of chemical engineering, Institute for Medical Engineering and Science, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge. For pioneering the area of non-viral gene therapy and cellular delivery. His work has resulted in fundamental scientific advances, over 500 papers, patents, and patent applications, and the creation of companies, products, and technologies that are now in the clinic.

    Kimberly Dawn Anderson-Erisman, PhD, professor, physical medicine and rehabilitation, Case Western Reserve University/MetroHealth System, Cleveland. For her 2004 seminal publication that challenged the dogma that ambulation was the top priority for people living with spinal cord injury (SCI), and redirection of SCI research toward upper limb, bowel, and bladder function. More recently, she led efforts to ensure that people with SCI participate in SCI research teams.

    Michael S. Avidan, MB BCh, FCA SA, Dr. Seymour and Rose T. Brown Professor of Anesthesiology, head of the department of anesthesiology, and professor of psychiatry and surgery, Washington University School of Medicine, St. Louis. For his international leadership in clinical anesthesiology research. He has designed and led large-scale, pragmatic clinical trials that have elucidated the role of clinical monitoring in the prevention of intraoperative awareness and delirium as well as the relationship of general anesthesia to neurocognitive outcomes of surgery. 

    Karen Bandeen-Roche, PhD, professor and emeritus chair, biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore. For enhancing the health and quality of life for older adults by developing innovative quantitative methods to improve measurements of complex disease states and to learn about patient trajectories and risks of major adverse events. Her methods have significantly advanced our understanding of functional capacity, disability, and frailty in aging. 

    Kurt Barnhart, MD, MSCE, William Shippen Jr. Professor of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. For establishing the standard of care for early pregnancy monitoring, and for pioneering novel management protocols to decrease morbidity from pregnancy-related complications and early pregnancy loss including ectopic pregnancy, which is the leading cause of first trimester maternal mortality worldwide. 

    Regina Barzilay, MS, PhD, School of Engineering Distinguished Professor of AI and Health, and AI lead, Jameel Clinic for Machine Learning and Health, Massachusetts Institute of Technology, Cambridge. For the development of machine learning tools that have been transformational for breast cancer screening and risk assessment, and for the development of molecular design tools broadly utilized for drug discovery. 

    Susan J. Baserga, MD, PhD, professor of molecular biophysics and biochemistry, of genetics, and of therapeutic radiology, molecular biophysics, and biochemistry, Yale University, New Haven, Conn. For pioneering the understanding of how ribosomes, the molecular factories that make proteins, assemble inside cells. Using a battery of approaches, she discovered a huge multi-molecular machine essential for ribosome formation in the cell nucleus. Components of this “processome” are implicated in a number of inherited human diseases. 

    Rashid Bashir, PhD, Grainger Distinguished Chair in Engineering, professor of bioengineering, University of Illinois at Urbana-Champaign, Champaign. For seminal contributions and visionary leadership in micro and nanoscale biosensors and diagnostics, bioengineering for early detection of infection and sepsis, and education in engineering-based medicine by helping to establish the world’s first engineering-based medical school at UIUC. 

    Bradley Bernstein, MD, PhD, chair of cancer biology and Richard and Nancy Lubin Family Chair, Dana-Farber Cancer Institute; and professor, departments of cell biology and pathology, Harvard Medical School, Boston. For landmark contributions to our understanding of chromatin structure and function, including the establishment of principles of gene poising, repression and long-range regulation, and the identification of epigenetic mechanisms that underlie stem cell potency and tumorigenesis. 

    Joseph R. Betancourt, MD, MPH, president, The Commonwealth Fund, New York City. For leading one of nation’s foremost health care philanthropies, and being one of the nation’s most accomplished and experienced scholars and practitioners of health care quality and equity improvement.  

    Marian E. Betz, MD, MPH, professor, emergency medicine, and founding director, Firearm Injury Prevention Initiative, University of Colorado, Aurora. For her firearms and suicide prevention expertise and engagement with community members, including gun owners and retailers, in developing interventions to save lives from firearm injuries. She leads groundbreaking research in injury prevention and has been an expert for national organizations and three White House administrations. 

    Sara Naomi Bleich, PhD, professor of public health policy, department of health policy and management, and vice provost for special projects, Harvard T.H. Chan School of Public Health, Harvard University, Boston. For her internationally renowned expertise on nutrition security, and for being an advocate for health equity. She is widely recognized for her leadership and policy-relevant research on prevention of obesity and other diet-related diseases, food insecurity, racial inequities in the U.S., and advancing equitable policy solutions for change. 

    John D. Carpten, PhD, chief scientific officer, City of Hope, Duarte, Calif. For leading the genomics field in understanding how racial and ethnic backgrounds affect cancer predisposition. He is internationally recognized for research in functional genomics, health disparities, and precision medicine. He has numerous national leadership roles and is the first African American to chair the National Cancer Advisory Committee. 

    Patrick M. Carter, MD, co-director, Institute for Firearm Injury Prevention; co-director, Injury Prevention Center; associate professor, department of emergency medicine, Medical School; and associate professor, department of health behavior and health education, School of Public Health, University of Michigan, Ann Arbor. For research and scholarship within the field of firearm injury prevention, including directing an Institute that is dedicated to advancing research on prevention-focused solutions to this public health problem, leading the NIH-funded Community Firearm Violence Prevention Network Coordinating Center, and directing a firearm injury prevention postdoctoral training program. 

    Timothy A. Chan, MD, PhD, chair, Global Center for Immunotherapy and Precision Immuno-Oncology; Sheikha Fatima Bint Mubarak Chair; and professor of medicine, Cleveland Clinic and Case Western Reserve University, Cleveland. For playing a key role in establishing the relationship between the number of mutations in a patient’s tumor and the success of immune checkpoint inhibitors. 

    Michael F. Chiang, MD, MA, director, National Eye Institute, National Institutes of Health, Bethesda, Md. For pioneering applications of biomedical informatics to ophthalmology in artificial intelligence, telehealth, pediatric retinal disease, electronic health records, and data science, including methodological and diagnostic advances in AI for pediatric retinopathy of prematurity, and for contributions to developing and implementing the largest ambulatory care registry in the United States. 

    Tumaini Rucker Coker, MD, MBA, professor and division head, general pediatrics, University of Washington, Seattle Children’s Hospital. For her leadership in advancing child health equity through scholarship in community-partnered design of innovative care models in pediatric primary care. Her work has transformed our understanding of how to deliver child preventive health care during the critical early childhood period to achieve equitable health outcomes and reduce disparities. 

    Theodore J. Corbin, MD, MPP, The Carol A. and Leo M. Henikoff, MD Presidential Professor; chairperson and professor, department of emergency medicine, Rush University Medical Center, Chicago. For his national leadership in firearm injury prevention. He focuses on community violence prevention and policy, has received numerous awards for his leadership, and currently serves as co-chair of the NAM Task Force on Preventing Firearm Injury and Violence. 

    Deidra C. Crews, MD, ScM, professor of medicine (nephrology), epidemiology, and nursing, Johns Hopkins University School of Medicine, Baltimore. For advancing equity and the social epidemiology of kidney disease. She has elucidated root causes of the disproportionate kidney disease burden among socially marginalized populations; used interventions to address social and behavioral risk factors for adverse outcomes; and informed guidelines for optimizing care for people with kidney failure. 

    Karina W. Davidson, PhD, MASc, senior vice president of research, Northwell Health; dean of academic affairs, Feinstein Institutes of Medical Research at Northwell Health; and Zucker Endowed Professor in Health Outcomes, departments of medicine, psychiatry, and cardiology, Zucker School of Medicine at Hofstra University/Northwell Health, New Hyde Park, N.Y. For being an influential implementation scientist, trialist, and practitioner of evidence-based behavioral medicine. As a central leader of national and global collaboratives, she has improved public health significantly by investigating the causal effects of behavior change. As chair of the U.S. Preventive Services Task Force, she affected the health care of millions. 

    Roger J. Davis, PhD, FRS, professor and chair, program in molecular medicine, University of Massachusetts Chan Medical School, Worcester. For his research leadership on mechanisms that mediate cellular stress responses. His seminal discoveries on the c-Jun NH2-terminal kinase (JNK) signaling pathway provide a foundation for understanding the molecular basis of metabolic inflammatory responses in the development of obesity, metabolic syndrome, and type 2 diabetes. 

    Luis Alberto Diaz Jr., MD, head, division of solid tumor oncology, department of medicine, Memorial Sloan Kettering Cancer Center, New York City. For pioneering efforts to provide the first definitive examples of circulating tumor DNA being successfully used as a cancer biomarker for screening, monitoring, and detection of occult disease, and for discovery of the therapeutic link between immunotherapy and genetics in Lynch Syndrome patients and others with mismatch repair-deficient tumors. 

    Gail D’Onofrio, MD, MS, Albert E. Kent Professor of Emergency Medicine, Yale School of Medicine; and professor of medicine core addiction and professor of epidemiology, Yale School of Public Health, New Haven, Conn. For foreseeing the exploding opioid misuse epidemic, identifying the opportunity during emergency care, and developing knowledge and policy to change the practice. Her studies on alcohol-related seizures, alcohol interventions, and emergency department-initiated buprenorphine are transformative. Her implementation science studies enhanced the migration of research into practice. 

    Kojo Seys John Elenitoba-Johnson, MD, inaugural chair, department of pathology and laboratory medicine, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York City. For pioneering lymphoma proteomics and being a top leader in precision and integrated diagnostics and their global democratization. His discoveries of therapeutically relevant recurrent genetic alterations and unbiased proteomic characterization of lymphoma have directly impacted patient care. 

    Sarah K. England, PhD, Alan A. and Edith L. Wolff Professor of Medicine, department of obstetrics and gynecology, Washington University School of Medicine, St. Louis. For contributions to the basic understanding of processes that underlie aberrant uterine activity leading to parturition and preterm birth. 

    M. Daniele Fallin, PhD, James W. Curran Dean of Public Health, Rollins School of Public Health, Emory University, Atlanta. For being an international leader in elucidating genetic, epigenetic, and environmental mechanisms for neuropsychiatric and developmental disorders, particularly autism, Alzheimer’s disease, and schizophrenia. As dean of public health at the Emory Rollins School, she contributes to population health efforts to recognize, understand, and prevent these neglected diseases. 

    Maurizio Fava, MD, chair, department of psychiatry, associate dean for clinical and translational research, and Slater Family Professor of Psychiatry, Harvard Medical School, Boston. For having contributed to the development of many novel antidepressant compounds throughout his career. He received research funding for over $110 million during the past 10 fiscal years, and has authored or co-authored over 900 original articles, with over 100,000 citations and an h index over 150. 

    Guoping Feng, PhD, James W. (1963) and Patricia T. Poitras Professor, brain and cognitive science; director, model systems and neurobiology, Stanley Center for Psychiatric Research; and Tan Yang Collective researcher and associate director, McGovern Institute for Brain Research, Massachusetts Institute of Technology; and member, Broad Institute of MIT and Harvard, Cambridge. For his breakthrough discoveries regarding the pathological mechanisms of neurodevelopmental and psychiatric disorders, providing foundational knowledges and molecular targets for developing effective therapeutics for mental illness such as OCD, ASD, and ADHD. 

    Sandy Feng, MD, PhD, professor of surgery in residence, and vice chair of research, department of surgery, University of California, San Francisco. For challenging the dogma of lifelong immunosuppression and reshaping the paradigm for the long-term management of people with liver transplants. Her leadership in ethics of deceased donor intervention is opening the door for innovative research to improve the quality and quantity of life-saving organs available for transplantation. 

    Christopher B. Forrest, MD, PhD, professor of pediatrics, Children’s Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia. For revolutionizing pediatric applied clinical research by founding PEDSnet, a network of 11 children’s hospitals that share clinical data and a >13 million patient database, providing uniquely large sample sizes for common and rare diseases, a model data-management infrastructure for pediatric clinical research, and a unique research training program. 

    Debra M. Furr-Holden, PhD, dean and professor of epidemiology, New York University School of Global Public Health, New York City. For her community-partnered research that has fueled multiple policy initiatives to improve behavioral health and eliminate racial, economic, and geographic disparities in intentional and unintentional injury including opioid-involved overdose death, gun violence, and community violence. 

    Susan L. Furth, MD, PhD, chief scientific officer, executive vice president, and Edmond F. Notebaert Endowed Chair in Pediatric Research, Children’s Hospital of Philadelphia; and professor, department of pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia. For defining the natural history and epidemiology of kidney disease in children, including rates of progression, and elucidating the impact of cardiovascular disease risk by race, social determinants, and cause of kidney disease through multi-center observational studies and randomized control trials. Her work has substantially impacted children’s health. 

    Richard L. Gallo, MD, PhD, distinguished professor and founding chair, department of dermatology, University of California, San Diego. For discovering that the skin produces antimicrobial peptides and acts with the microbiome to protect against infection and regulate inflammation. His seminal observations in these fields have uncovered aspects of the pathogenesis of several diseases including atopic dermatitis, rosacea, and psoriasis, improving current approaches to therapy. 

    Francisco A.R. García, MD, MPH, deputy county administrator and chief medical officer, Pima County; and professor emeritus of public health, University of Arizona, Tucson. For being an internationally recognized expert in border health, emergency preparedness, and women’s reproductive health with more than 24 years of experience in public health and human services administration. He leads teams that develop innovative, collaborative, multi-sectoral approaches to the complex problems in vulnerable communities. 

    Cheryl L. Giscombe, PhD, PMHNP, RN, FAAN, FABMR, distinguished tenured professor and interim senior associate dean of academic affairs, School of Nursing, University of North Carolina, Chapel Hill. For influencing national guidelines as a leading scholar on mental health, resilience, clinician wellness, and mind-body research. Her groundbreaking accomplishments include development of the Interprofessional Leadership Institute for Mental Health Equity, the “Superwoman Schema” theory, and biopsychosocial solutions for stress-related health inequities. 

    Céline R. Gounder, MD, senior fellow and editor-at-large for public health, KFF Health News; medical contributor, CBS News; and clinical associate professor of internal medicine and infectious diseases, New York University Grossman School of Medicine and NYC Health + Hospitals/Bellevue, New York City. For being one of the world’s leading experts in communication about science, medicine, and public health. She has won awards for coverage of health inequities and the COVID, Ebola, Zika, opioid, gun-violence, and disinformation epidemics. 

    David C. Grabowski, PhD, professor, health care policy, Harvard Medical School, Boston. For his leadership, prominence, and contributions to the field of health economics, for elucidating novel trends in long-term and post-acute care quality, and identifying contradictory payment policies for Medicare and Medicaid, and for his work on the determinants of COVID-19 in nursing home deaths resulting in policy changes. 

    Eric D. Green, MD, PhD, director, National Human Genome Research Institute (NHGRI), National Institutes of Health, Bethesda, Md. For leading the development of technologies and tools for translating genomics to clinical practice. Globally, he has pioneered cooperation to advance genomic fluency and precision medicine. In parallel, he has modeled diversity and inclusion in NHGRI senior leadership and workforce training programs. 

    Justin Hanes, PhD, Lewis J. Ort Professor of Ophthalmology, Wilmer Eye Institute, and professor of biomedical engineering, chemical and biomolecular engineering, neurosurgery, oncology, and pharmacology and molecular sciences, Johns Hopkins University, Baltimore. For pioneering discoveries and inventions of innovative drug delivery technologies, especially mucosal, ocular, and central nervous system drug delivery systems; and for international leadership in research and education at the interface of engineering, medicine, and entrepreneurship, leading to clinical translation of drug delivery technologies. 

    Richard J. Hatchett, MD, chief executive officer, Coalition for Epidemic Preparedness Innovations (CEPI), Oslo, Norway. For extraordinary leadership in national and global public health preparedness. His many contributions include conceiving the Medical Reserve Corps after 9/11, pioneering social distancing strategies, helping to lead the 2009 Influenza Pandemic response, serving as first CEO of CEPI, and advancing equitable COVID-19 vaccine distribution by co-founding COVAX. 

    Jiang He, MD, PhD, professor and Joseph S. Copes Chair in Epidemiology, and director, Translational Science Institute, Tulane University, New Orleans. For transforming cardiovascular disease (CVD) prevention efforts worldwide. After landmark studies documenting key determinants for CVD in the U.S., China, and elsewhere, he designed and rigorously tested highly effective and scalable interventions in resource-constrained settings. His research is creative, impactful, and transformative on a global scale. 

    Said A. Ibrahim, MD, MPH, MBA, senior vice president, medicine service line; chair, department of medicine; and David J. Greene Professor of Medicine, Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, N.Y. For his seminal health services research on racial disparities in elective joint replacement that has provided a national model for advancing health equity research beyond the identification of inequities and toward their remediation, and for his research that has been leveraged to engage diverse and innovative emerging scholars. 

    Thomas V. Inglesby, MD, director, Center for Health Security, and professor, department of environmental health and engineering, Johns Hopkins Bloomberg School of Public Health; and joint appointment in medicine, Johns Hopkins School of Medicine, Baltimore. For helping to establish and shape the field of public health preparedness and response, and for being an internationally respected voice during COVID. He’s been a public health leader for U.S. Department of Health and Human Services and the White House and influenced national and international policy, creating valuable collaborations and networks around the world. 

    Darrell J. Irvine, PhD, Underwood-Prescott Professor, department of biological engineering and department of materials science and engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge. For the development of novel methods for delivery of immunotherapies and vaccines for cancer and infectious diseases. 

    Ursula B. Kaiser, MD, chief, division of endocrinology, diabetes, and hypertension, and George W. Thorn, MD, Distinguished Chair in Endocrinology, Brigham and Women’s Hospital; and professor of medicine, Harvard Medical School, Boston. For being an internationally recognized leader in reproductive neuroendocrinology. Her major scientific accomplishments include the unraveling of genetic and molecular mechanisms controlling pubertal timing and gonadotropin-releasing hormone activation and the regulation of luteinizing hormone and follicle-stimulating hormone secretion. 

    Joneigh S. Khaldun, MD, MPH, FACEP, vice president and chief health equity officer, CVS Health, and staff physician, Henry Ford Health, Detroit. For her national leadership in emergency medicine and public health and advancing effective strategies to improve the health of historically marginalized populations. She led Michigan’s COVID-19 response, as well as the Detroit Health Department’s strategy contributing to the city’s lowest recorded infant mortality rate. As an appointee to President Biden’s COVID-19 Health Equity Task Force, she helped advance recommendations for improving the country’s response to current and future pandemics. 

    Christopher F. Koller, MPPM, MAR, president, Milbank Memorial Fund, New York City. For influencing the alignment of private and public health care policy to achieve systemic progress in population health and cost-effectiveness. The reforms he led as Rhode Island’s Health Insurance Commissioner have had national influence. 

    Wilbur A. Lam, MD, PhD, professor and W. Paul Bowers Research Chair, Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology; and professor, department of pediatrics, and associate dean of innovation, Emory University School of Medicine, Atlanta. For outstanding contributions in blood biophysics, in vitro models of hematologic diseases, and point-of-care, home-based, and/or smartphone-enabled diagnostics that are changing the management of pediatric and blood disorders. He also leads efforts to assess diagnostic tests (including those used during the COVID-19 pandemic) for the NIH and entire country. 

    Steven D. Leach, MD, professor of molecular and systems biology, surgery, and medicine; Preston T. and Virginia R. Kelsey Distinguished Chair in Cancer; and director, Dartmouth Cancer Center, Dartmouth Geisel School of Medicine, Lebanon, N.H. For being an international leader in pancreatic cancer research, having made seminal research contributions in pancreatic cancer surgery, biology, genomics, and therapy over the past three decades. 

    Jeannie T. Lee, MD, PhD, professor of genetics, department of molecular biology, Massachusetts General Hospital; and department of genetics, Harvard Medical School, Boston. For research that has been central for understanding the roles of non-coding RNA in gene regulation. Using X-chromosome inactivation as a model, her investigations into extensive transcription of non-coding RNA are uncovering potential therapeutics to treat human diseases, including autism spectrum disorders, Rett Syndrome, and Fragile X Syndrome. 

    Lois K. Lee, MD, MPH, associate professor of pediatrics and emergency medicine, Harvard Medical School; and senior associate in pediatrics, division of emergency medicine, Boston Children’s Hospital, Boston. For foundational research on firearm injuries and being the lead author for the American Academy of Pediatrics 2022 Technical Report/Policy Statement on pediatric firearm injury prevention. In an area lacking major research support, she conducted and translated rigorous injury science for policymakers, leading to thousands of prevented injuries. 

    Kirsten E. Lyke, MD, professor of medicine, Center for Vaccine Development and Global Health, and director, Malaria Vaccine and Challenge Unit, University of Maryland, Baltimore. For internationally recognized contributions to vaccine development against global (malaria and dengue) and emerging (Ebola and COVID-19) infectious diseases, and for leadership in human challenge models, optimizing and operationalizing tools that allow down-selection of candidate vaccines and monoclonal antibodies against malaria and dengue. 

    Yvonne (Bonnie) Maldonado, MD, Taube Professor of Global Health and Infectious Diseases; professor of pediatrics and epidemiology and population health, Stanford University, Stanford, Calif. For her contributions in the epidemiology and control of pediatric infectious diseases, including polio and measles elimination from the Americas, prevention of maternal-infant HIV transmission, and the national COVID-19 pandemic response. She is a first-generation Latina and a role model for her academic accomplishments. 

    Miriam Merad, MD, PhD, chair, department of immunology and immunotherapy, and director, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York City. For her groundbreaking discoveries in immunology, establishing for the first time that tissue-resident macrophages form an independent lineage that arises and is maintained independently of adult hematopoiesis, and have unique functional attributes that promote tissue integrity and tissue repair, response to infection, and contribute to tumor outcome. 

    Timothy M. Miller, MD, PhD, David Clayson Professor of Neurology and vice chair of research, Washington University, St. Louis. For defining pathophysiology and developing a novel RNA-targeted therapeutic approach for treating neurological diseases, which he has pioneered and shown successful in amyotrophic lateral sclerosis and dementias. His blueprint for drug design and clinical trial application is now serving as a model in other neurologic disease programs. 

    Robert Avery Montgomery, MD, DPhil, FACS, H. Leon Pachter Chair and professor of surgery, department of surgery, and director, NYU Langone Transplant Institute, NYU Langone Health, New York City. For significant contributions to the field of transplantation. He led the team that performed the first successful genetically edited pig-to-human kidney xenotransplant. He invented the type of “kidney swap” that is responsible for over a thousand kidney transplants a year. 

    Gerardo Moreno, MD, MSHS, chair and professor, department of family medicine, University of California, Los Angeles. For being one of the most influential young Latino academic leaders in family medicine and health care. He has implemented successful research initiatives and programs that enable and mentor minority students and advocates for state and federal policies that diversify the health care workforce, anchored in caring for high-risk patients in underserved communities. 

    Siddhartha Mukherjee, MD, DPhil, associate professor of medicine, department of medicine, division of oncology, Columbia University of Medicine, New York City. For contributing important research in the immunotherapy of myeloid malignancies, such as acute myeloid leukemia, for establishing international centers for immunotherapy for childhood cancers, and for the discovery of tissue-resident stem cells. His book, “The Emperor of All Maladies,” won the Pulitzer Prize and was nominated by Time as one of the century’s 100 most influential books, introducing millions to modern cancer research. 

    Lisa A. Newman, MD, MPH, professor of surgery, chief, breast surgery section, and executive director and founder, International Center for the Study of Breast Cancer Subtypes, Weill Cornell Medicine and New York Presbyterian Hospital Network, New York City. For her efforts to address and eliminate breast cancer disparities across the world and whose research on characterizing hereditary susceptibility for triple negative breast cancer associated with African ancestry have earned worldwide acclaim. 

    Igho Ofotokun, MD, MSc, FIDSA, Grady Distinguished Professor of Medicine, School of Medicine, and professor of behavioral, social, and health education sciences, Rollins School of Public Health, Emory University, Atlanta. For being a leading authority on the burden of chronic HIV and other infections in vulnerable populations. He promotes innovative strategies to mitigate this burden and enhance healthy aging. He leverages his platform to promote women and minorities in the biomedical workforce globally. 

    Herminia Palacio, MD, MPH, president and CEO, Guttmacher Institute, New York City. For advancing health care delivery in the U.S. through leadership roles in nonprofits, government, philanthropy, and academia. As examples, she leads one of the most important research and policy institutes for reproductive rights in the U.S. and developed a health access program in New York City serving over 100,000 people. 

    Desmond U. Patton, PhD, MSW, Schwartz University Professor of Social Policy, Communications, and Psychiatry; founding director, SAFElab; and chief strategy officer, School of Social Policy and Practice, University of Pennsylvania, Philadelphia. For being the founding director of the SAFElab, a research lab focused on the ways in which youth of color navigate violence online and offline. He combines innovative and rigorous data science and social work approaches to understand the mechanisms of violence, firearm violence, joy, and grief. 

    Raina K. Plowright, PhD, Rudolf J. and Katharine L. Steffen Professor, department of public and ecosystem health, College of Veterinary Medicine, Cornell Atkinson Center for Sustainability, Cornell University, Ithaca, N.Y. For leadership in studying the impact of climate and land use change on infectious diseases emergence. She defined the spatial and temporal mechanisms underlying spillover of Hendra virus from bats into domestic animal and human populations. Her mechanistic work at the interface of ecology and disease is critical for preventing future pandemics. 

    Keshia M. Pollack Porter, PhD, MPH, Bloomberg Centennial Professor and Bloomberg Centennial Chair, department of health policy and management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore. For her national leadership and major contributions to research, practice, and education related to health in all policies, and development of methodologies that promote health and equity considerations in policy decisions across multiple sectors, including transportation, housing, and education. 

    Kristy Red-Horse, PhD, investigator, Howard Hughes Medical Institute; and professor, department of biology, and professor, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, Calif. For research on how coronary vessels of the heart develop during embryogenesis and how they regenerate following cardiac injury. Her long-term goal is to discover novel developmental mechanisms while contributing knowledge toward the advancement of clinical treatments for cardiovascular disease. 

    Teri Reynolds, MD, MS, PhD, unit head, World Health Organization, Geneva, Switzerland. For establishing the first WHO emergency care program and developing WHO’s Basic Emergency Care and Global Emergency and Trauma Care Initiative, active in 60 countries. She leads WHO’s guidance on universal health coverage packages and essential health services during crisis. Her academic contributions include extraordinary research collaborations across Africa and beyond. 

    Joseph B. Richardson Jr., PhD, MA, MPower Professor of African American Studies and Anthropology, department of African American studies and department of anthropology, University of Maryland, College Park. For being a nationally and internationally recognized pioneer in research on gun violence, firearm injury, trauma, and interventions. His work includes translating science into the development of innovative interventions to reduce gun violence and firearm-related morbidity and mortality, especially as it impacts youth in poverty and Black men. 

    Lainie Friedman Ross, MD, PhD, dean’s professor and chair, department of health humanities and bioethics, director, Paul M. Schyve MD Center for Bioethics, and professor, departments of pediatrics and philosophy, University of Rochester, Rochester, N.Y.; and Carolyn and Matthew Bucksbaum Professor Emerita, University of Chicago. For her role in developing the living kidney paired exchange program, which now accounts for over 1,000 kidney transplants annually. Ross has also proposed a pediatric decision-making framework that is one of four models incorporated into the American Academy of Pediatrics policy on decision-making in pediatric practice. 

    Ali Rowhani-Rahbar, MD, MPH, PhD, Bartley Dobb Endowed Professor for the Study and Prevention of Violence, department of epidemiology, University of Washington, Seattle. For being a national public health leader whose innovative and multidisciplinary research to integrate data across the health care system and criminal legal system has deepened our understanding of the risk and consequences of firearm-related harm and informed policies and programs to reduce its burden especially among underserved communities and populations. 

    Mustafa Sahin, MD, PhD, professor, department of neurology, Boston Children’s Hospital, Boston. For world-leading expertise in the neurobiology of autism and a pioneer in translational studies for neurogenetic disorders. Work in the Sahin lab has identified the mechanisms by which tuberous sclerosis leads to neuronal mis-wiring and led to the identification of potential therapies for this and related disorders. 

    Joseph V. Sakran, MD, MPH, MPA, FACS, executive vice chair of surgery and director of clinical operations, and associate professor of surgery and nursing, Johns Hopkins Medicine, Baltimore. For being a nationally recognized trauma surgeon whose innovative work and exceptional leadership in firearm injury prevention has been most instrumental in establishing the urgency and intellectual foundation to drive research and evidence-based policy change at the local, state, and federal levels. 

    Rebecca Anne Seguin-Fowler, PhD, RDN, co-director, Institute for Advancing Health Agriculture, and professor of nutrition, Texas A&M University, College Station. For being a leading authority on community-engaged research in the areas of diet and physical activity interventions for obesity and chronic disease prevention among rural, low-income, older adult, minority, and other at-risk, underserved populations. Her innovative work and leadership have advanced knowledge related to social and environmental contextual factors to advance implementation and dissemination research to achieve health equity. 

    Morgan Sheng, MBBS, PhD, professor, department of brain and cognitive sciences, Massachusetts Institute of Technology; core institute member, Broad Institute of MIT and Harvard, Cambridge. For transforming the understanding of excitatory synapses. He revealed the postsynaptic density as a protein network controlling synaptic signaling and morphology; established the paradigm of signaling complexes organized by PDZ scaffolds; and pioneered the concept of localized regulation of mitochondria, apoptosis, and complement for targeted synapse elimination. 

    Catherine Y. Spong, MD, professor and Paul C. MacDonald Distinguished Chair, department of obstetrics and gynecology, University of Texas Southwestern Medicine Center, Dallas. For her international leadership, both at NIH during the ZIKA epidemic and at UT-Southwestern during the COVID-19 pandemic, that clearly demonstrated that clinical research translates into improved care for women and families. 

    Timothy A. Springer, PhD, senior investigator, program in cellular and molecular medicine, and Latham Family Professor, professor of biological chemistry and molecular pharmacology, and professor of medicine, Boston Children’s Hospital/Harvard Medical School, Boston. For his research on receptor-ligand interactions and transmembrane signal transmission that are relevant to immunology, hemostasis, and human disease using structural, cell biological, and single molecule techniques. Molecules studied include integrins and their ligands, TGF-β, the epidermal growth factor receptor, vaccine targets in malaria, and von Willebrand factor (4750). 

    Brent R. Stockwell, PhD, William R. Kenan Jr. Professor of Biological Sciences; chair, department of biological sciences, and professor of chemistry, Columbia University; and professor of pathology and cell biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York City. For his discovery of ferroptosis, a form of iron-driven, oxidative cell death involving lipid peroxidation. He defined its features, mechanistic basis, the key genes and proteins and inhibitors that regulate it, and tools to study it. He identified roles of ferroptosis in neurodegenerative diseases and cancer, suggesting novel therapeutic strategies. 

    Rudolph Emile Tanzi, PhD, Joseph P. and Rose F. Kennedy Professor of Neurology, Harvard University, and vice chair of neurology, Massachusetts General Hospital, Boston. For being a pioneer and world leader in the areas of Alzheimer’s disease (AD), neurogenetics, and translating pathogenetic mechanisms underlying neurodegenerative diseases into novel therapeutics. He discovered numerous AD genes including the first three and developed the first complete human brain organoid model of AD, greatly accelerating drug discovery. 

    Julian F. Thayer, PhD, distinguished professor, department of psychological science, University of California, Irvine. For groundbreaking research and theory in understanding how stress, including racism, impacts autonomic nervous system dynamics and influence disease and the process of aging. Specifically, he has mapped out the complex mechanisms of how stress-related dysregulation of the vagal-neural axis can lead to early cardiovascular disease. 

    Methodius Gamuo Tuuli, MD, MPH, MBA, Chace-Joukowsky Professor of Obstetrics and Gynecology; chair, obstetrics and gynecology, Warren Alpert Medical School, Brown University; chief of obstetrics and gynecology, Women and Infants Hospital of Rhode Island; and executive chief of obstetrics and gynecology, Care New England, Providence, R.I. For employing large multicenter trials and cohort studies, in the U.S. and globally, to generate evidence for clinical practice and policy to prevent adverse obstetric outcomes including surgical site infection after cesarean, management of labor, and medical complications in pregnancy, while building research capacity and mentoring diverse scholars. 

    Robert Otto Burciaga Valdez, PhD, MHSA, director, Agency for Healthcare Research and Quality,  U.S. Department of Health and Human Services, Rockville, Md. For internationally recognized expertise in health services research and whose research has generated actionable knowledge. His government service, mentoring, and academic leadership have all advanced our ability to measure and improve access, quality, and health care outcomes, especially for children and historically excluded communities. 

    Terry L. Vanden Hoek, MD, FACEP, professor and department chair of emergency medicine, professor of physiology and biophysics, professor of pharmacology and regenerative medicine, and director, Center for Advanced Resuscitation Medicine, Center for Cardiovascular Research, UI Health, University of Illinois College of Medicine, Chicago. For his leadership in CPR that has changed worldwide practice and significantly improved cardiac arrest survival in Illinois. He has received over $30 million of extramural funding to improve care for vulnerable populations and his work ranges from novel peptide development for cardiac arrest treatment to artificial intelligence-monitoring for COVID-19 patient protection. 

    Robert H. Vonderheide, MD, DPhil, director, Abramson Cancer Center; John H. Glick Abramson Cancer Center Director’s Professor; vice dean, Cancer Programs, Perelman School of Medicine; and vice president, Cancer Programs, University of Pennsylvania Health System, University of Pennsylvania, Philadelphia. For developing immune combination therapies for patients with pancreatic cancer by driving proof-of-concept from lab to clinic, then leading national, randomized clinical trials for therapy, maintenance, and interception; and for improving access of minority individuals to clinical trials while directing an NCI comprehensive cancer center. 

    Emily Ai-hua Wang, MD, MAS, professor of medicine and of public health, and director, SEICHE Center for Health and Justice, Yale University School of Medicine, New Haven, Conn. For elucidating the health impacts of incarceration and partnering with formerly incarcerated people to study interventions to prevent health harms. Her work illuminates that the achievement of health equity requires ending mass incarceration and the vital role that health systems can play in decarceration to improve population health. 

    Jennifer A. Wargo, MD, MMSc, R. Lee Clark Endowed Professor of Surgical Oncology and Genomic Medicine, and founder and director, Platform for Innovative Microbiome and Translational Research, University of Texas MD Anderson Cancer Center, Houston. For making fundamental and practice-changing contributions to our understanding of the response and resistance of melanoma to targeted therapy and immunotherapy. She pioneered the role of the tumor and gut microbiome in tumor biology and therapeutic response and translated these paradigmatic discoveries into novel clinical trials. 

    Daniel W. Webster, ScD, MPH, Bloomberg Professor of American Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore. For leading groundbreaking research that has shaped policies at all levels of government and the gun violence prevention field. Over 30 years, his research has clearly and unwaveringly identified policies that prevent gun violence and suicides and informed community violence intervention programs. 

    Jennifer L. West, PhD, dean, School of Engineering and Applied Science, and professor of biomedical engineering, University of Virginia, Charlottesville. For the invention, development and translation of novel biomaterials including bioactive, photopolymerizable hydrogels and theranostic nanoparticles. 

    Jedd D. Wolchok, MD, PhD, director, Sandra and Edward Meyer Cancer Center, department of medicine, Weil Cornell Medicine, New York City. For his commitment to understanding the role of the immune system in cancer therapy. He has led several practice-changing trials establishing the use of immune checkpoint blockade for melanoma and other cancers. He has also led impactful efforts defining the mechanistic basis for sensitivity to these therapies. 

    Phillip D. Zamore, PhD, investigator, Howard Hughes Medical Institute; and Gretchen Stone Cook Professor of Biomedical Sciences, and chair and professor, RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester. For making fundamental contributions to the understanding of RNAi, developing the first biochemical systems to study siRNAs, miRNAs, and their protein partners. His seminal discoveries explained how small RNAs are made and repress genes, transposons, and viruses. He has used these insights to develop novel RNA-based therapies for human diseases. 

    Hongkui Zeng, PhD, executive vice president and director, Allen Institute for Brain Science, Seattle. For her leadership in investigating cell types and connections in the mammalian brain. Her team has generated large-scale, open-access datasets and tools to accelerate neuroscience discovery. By systematically characterizing the transcriptome, morphology, and physiology of individual neurons, her work has led to transformative understanding of cell type diversity. 

    Yi Zhang, PhD, Fred S. Rosen Chair Professor, department of pediatrics, Boston Children’s Hospital; professor, department of genetics, Harvard Medical School; and associate member, Broad Institute of MIT and Harvard, Boston. For making fundamental contributions to the epigenetics field through systematic identification and characterization of chromatin modifying enzymes, including EZH2, JmjC, and Tet. His proof-of-principle work on EZH2 inhibitors led to the founding of Epizyme and eventual making of tazemetostat, a drug approved for epithelioid sarcoma and follicular lymphoma.

    Newly elected international members and their election citations are: 

    Charles O. Agyemang, PhD, MPH, professor, global migration, ethnicity, and health, University of Amsterdam, Netherlands. For providing novel insight into the effects of global migration on obesity, diabetes, and cardiovascular diseases. He established the RODAM study on Africa-to-Europe migration. His team conducted the first comprehensive research on health outcomes in African migrants in Europe, utilizing epidemiological, social, clinical, and molecular tools. 

    Celso Arango, MD, PhD, director, Institute of Psychiatry and Mental Health, and head, department of child and adolescent psychiatry, Hospital General Universitario Gregorio Marañón, Madrid, Spain. For facilitating the change in FDA, EMA policies for psychotropic drugs for pediatric indications. He was influential in facilitating regulatory agency policies changes requiring companies to conduct pediatric investigations as part of a new drug’s development. He has led 15 clinical trials in prevention and treatment of mental disorders in children and adolescents. 

    Lukoye Atwoli, MBChB, MMed Psych, PhD, professor and dean, Medical College East Africa; and associate director, Brain and Mind Institute, The Aga Khan University Medical College, East Africa, Nairobi, Kenya. For contributions to mental health care, policy, education, and epidemiology globally, for leading African and global medical and psychiatric associations, for leading two innovative medical schools in Africa as dean, and for co-chairing the National Academies of Sciences, Engineering, and Medicine’s Board on Global Health, among other achievements. 

    Nils Brose, PhD, director, department of molecular neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany. For his pioneering work that has provided key insights into the molecular topography of synaptic signaling. His discoveries of key principles of synapse formation and transmitter release form the basis of our understanding of how neuronal microcircuits are organized and operate, and how their malfunction causes neurological and psychiatric disorders. 

    Hélène Carabin, DVM, MSc, PhD, professor and Canada Research Chair in Epidemiology and One Health, department of microbiology and pathology, and faculty of veterinary medicine, department of social and preventative medicine, School of Public Health, Université de Montréal, Montreal, Canada. For her internationally recognized leadership in the epidemiology and transmission of neglected infections and neurological disease using a One Health approach. She currently serves on the scientific advisory committee on Global Health for Canada. Her epidemiological approaches have contributed to establishment of effective measures of zoonotic disease impact and global burden of disease estimates. 

    Daniel Drucker, MD, professor of medicine, department of medicine, University of Toronto; and senior scientist, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, Canada. For pioneering studies of gastrointestinal hormone action and elucidating multiple novel metabolic actions of GLP-1, DPP-4, and GLP-2. His discoveries enabled development of three new classes of medications (GLP-1R agonists, DPP4 inhibitors, GLP-2R agonists) that have transformed the treatment of diabetes, obesity, and short bowel syndrome. 

    Christian T. Happi, MSc, PhD, distinguished professor, Redeemer’s University; and director, African Center of Excellence for Genomics of Infectious Diseases (ACEGID), Ede, Nigeria. For his tangible impact on infectious disease research in Africa. He has established critical programs and made important scientific contributions to malaria, Lassa fever, Ebola, mpox, yellow fever, and COVID-19 research. He led the effort to sequence the first full SARS-Cov-2 genome in Africa, which guided public health interventions, and is developing an early warning system that could stop the next pandemic before it starts. 

    Marta Imamura, MD, PhD, associate professor, department of legal medicine, bioethics, work medicine and physical medicine and rehabilitation, University of São Paulo School of Medicine, São Paulo, Brazil. For her internationally recognized research exploring the role of central and peripheral sensitization and neurophysiological biomarkers contributing to chronic disabling myofascial (musculoskeletal) pain. This work is being evaluated for use by the Brazilian Unified Health System for assessment and non-pharmacological treatment of this pain. 

    Anne M. Johnson, MB BS, MSc, MD, professor of infectious disease epidemiology, Institute for Global Health, University College London, London, United Kingdom. For being a leading clinical epidemiologist on transmission dynamics and prevention of HIV, sexually transmitted infections, and more recently COVID-19. She has led the British National Surveys of Sexual Lifestyles. Her research has focused on understanding behavioral epidemiology and has contributed broadly to public health policy. 

    Jens Nielsen, PhD, drtechn, drmedhc, CEO, BioInnovation Institute, Copenhagen, Denmark; professor, department of life science, Chalmers University of Technology, Gothenburg, Sweden. For developing a systems biology approach for studying human metabolism with the objective to identify novel biomarkers and drug targets for metabolic diseases like type-2-diabetes, liver diseases and cancer. Several of his findings have been translated for use in the clinic for improved diagnosis. 

    Contact: 
    Dana Korsen, Director of Media Relations
    Office of News and Public Information
    202-334-2138; e-mail [email protected]

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  • NIH Study Illuminates Origins of Lung Cancer in Never Smokers

    NIH Study Illuminates Origins of Lung Cancer in Never Smokers

    Monday, September 6, 2021

    NIH study illuminates origins of lung cancer in never smokers

    Illustration of lungs made up of DNA sequences. A magnifying glass hovers over a portion of a DNA sequence showing a mutational change.

    National Cancer Institute

    A genomic analysis of lung cancer in people with no history of smoking has found that a majority of these tumors arise from the accumulation of mutations caused by natural processes in the body. This study was conducted by an international team led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and describes for the first time three molecular subtypes of lung cancer in people who have never smoked.

    These insights will help unlock the mystery of how lung cancer arises in people who have no history of smoking and may guide the development of more precise clinical treatments. The findings were published September 6, 2021, in Nature Genetics.

    “What we’re seeing is that there are different subtypes of lung cancer in never smokers that have distinct molecular characteristics and evolutionary processes,” said epidemiologist Maria Teresa Landi, M.D., Ph.D., of the Integrative Tumor Epidemiology Branch in NCI’s Division of Cancer Epidemiology and Genetics, who led the study, which was done in collaboration with researchers at the National Institute of Environmental Health Sciences, another part of NIH, and other institutions. “In the future we may be able to have different treatments based on these subtypes.”

    Lung cancer is the leading cause of cancer-related deaths worldwide. Every year, more than 2 million people around the world are diagnosed with the disease. Most people who develop lung cancer have a history of tobacco smoking, but 10% to 20% of people who develop lung cancer have never smoked. Lung cancer in never smokers occurs more frequently in women and at an earlier age than lung cancer in smokers.

    Environmental risk factors, such as exposure to secondhand tobacco smoke, radon, air pollution, and asbestos, or having had previous lung diseases, may explain some lung cancers among never smokers, but scientists still don’t know what causes the majority of these cancers.

    In this large epidemiologic study, the researchers used whole-genome sequencing to characterize the genomic changes in tumor tissue and matched normal tissue from 232 never smokers, predominantly of European descent, who had been diagnosed with non-small cell lung cancer. The tumors included 189 adenocarcinomas (the most common type of lung cancer), 36 carcinoids, and seven other tumors of various types. The patients had not yet undergone treatment for their cancer.

    The researchers combed the tumor genomes for mutational signatures, which are patterns of mutations associated with specific mutational processes, such as damage from natural activities in the body (for example, faulty DNA repair or oxidative stress) or from exposure to carcinogens. Mutational signatures act like a tumor’s archive of activities that led up to the accumulation of mutations, providing clues into what caused the cancer to develop. A catalogue of known mutational signatures now exists, although some signatures have no known cause. In this study, the researchers discovered that a majority of the tumor genomes of never smokers bore mutational signatures associated with damage from endogenous processes, that is, natural processes that happen inside the body.

    As expected, because the study was limited to never smokers, the researchers did not find any mutational signatures that have previously been associated with direct exposure to tobacco smoking. Nor did they find those signatures among the 62 patients who had been exposed to secondhand tobacco smoke. However, Dr. Landi cautioned that the sample size was small and the level of exposure highly variable.

    “We need a larger sample size with detailed information on exposure to really study the impact of secondhand tobacco smoking on the development of lung cancer in never smokers,” Dr. Landi said.

    The genomic analyses also revealed three novel subtypes of lung cancer in never smokers, to which the researchers assigned musical names based on the level of “noise” (that is, the number of genomic changes) in the tumors. The predominant “piano” subtype had the fewest mutations; it appeared to be associated with the activation of progenitor cells, which are involved in the creation of new cells. This subtype of tumor grows extremely slowly, over many years, and is difficult to treat because it can have many different driver mutations. The “mezzo-forte” subtype had specific chromosomal changes as well as mutations in the growth factor receptor gene EGFR, which is commonly altered in lung cancer, and exhibited faster tumor growth. The “forte” subtype exhibited whole-genome doubling, a genomic change that is often seen in lung cancers in smokers. This subtype of tumor also grows quickly.

    “We’re starting to distinguish subtypes that could potentially have different approaches for prevention and treatment,” said Dr. Landi. For example, the slow-growing piano subtype could give clinicians a window of opportunity to detect these tumors earlier when they are less difficult to treat. In contrast, the mezzo-forte and forte subtypes have only a few major driver mutations, suggesting that these tumors could be identified by a single biopsy and could benefit from targeted treatments, she said.

    A future direction of this research will be to study people of different ethnic backgrounds and geographic locations, and whose exposure history to lung cancer risk factors is well described.

    “We’re at the beginning of understanding how these tumors evolve,” Dr. Landi said. This analysis shows that there is heterogeneity, or diversity, in lung cancers in never smokers.”

    Stephen J. Chanock, M.D., director of NCI’s Division of Cancer Epidemiology and Genetics, noted, “We expect this detective-style investigation of genomic tumor characteristics to unlock new avenues of discovery for multiple cancer types.”

    The study was conducted by the Intramural Research Program of NCI and National Institute of Environmental Health Sciences.

    About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call NCI’s contact center, the Cancer Information Service, at 1-800-4-CANCER (1-800-422-6237).

    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 www.nih.gov.

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  • NIH Researchers Find Many People Want Secondary Genomic Findings After Initially Refusing

    NIH Researchers Find Many People Want Secondary Genomic Findings After Initially Refusing

    A study published today by researchers at the National Institutes of Health revealed that about half of individuals who said they don’t want to receive secondary genomic findings changed their mind after their healthcare provider gave them more detailed information. The paper, published in Genomics in Medicine, examines people’s attitudes about receiving secondary genomic findings related to treatable or preventable diseases.

    The study was led by scientists at the National Human Genome Research Institute (NHGRI) and the National Institute of Environmental Health Sciences (NIEHS), both part of NIH.

    Animation of patient filling out an informed consent form and checking the “YES” checkboxes for both Expected Outcome and Secondary Findings. Credit: Ernesto del Aguila III, NHGRI.

    With the broader adoption of genome sequencing in clinical care, researchers and the bioethics community are considering options for how to navigate the discovery of secondary genomic findings. Secondary findings that come out of genome sequencing reflect information that is separate from the primary reason for an individual’s medical care or participation in a study. For example, the genomic data of a patient who undergoes genome sequencing to address an autoimmune problem might reveal genomic variants that are associated with a heightened risk for breast cancer.

    Based on the American College of Medical Genetics and Genomics recommendations in 2021, individuals who have their genomes sequenced for a clinical reason should also be screened for genomic variants in 73 genes, including BRCA1 and BRCA2, both of which are linked to an increased risk of breast and ovarian cancer. All 59 genes are associated with treatable or potentially severe diseases. Proponents of a person’s right to not know their secondary genomic findings have argued that, to maintain autonomy, individuals should have the opportunity to decide whether to be provided information about genomic variants in these additional genes.

    “Because these genomic findings can have life-saving implications, we wanted to ask the question: Are people really understanding what they are saying no to? If they get more context, or a second opportunity to decide, do they change their mind?” said Benjamin Berkman, J.D., M.P.H., deputy director of the NHGRI Bioethics Core and senior author on the study.

    The research group worked with participants from the Environmental Polymorphisms Registry, an NIEHS study examining how genetic and environmental factors influence human health. Out of 8,843 participants, 8,678 elected to receive secondary genomic findings, while 165 opted out. Researchers assessed those 165 individuals to determine how strongly and consistently they maintained their “right not to know” decision. The researchers wanted to determine whether providing additional information to people about their genomic variants influenced their decision and to better understand why some people still refused their secondary genomic findings after they received the additional information.

    Following the intervention, the researchers found that the 165 people sorted into two groups: “reversible refusers” who switched their decision to accept to know their secondary genomic findings and “persistent refusers” who still refused.

    Because these genomic findings can have life-saving implications, we wanted to ask the question: Are people really understanding what they are saying no to? If they get more context, or a second opportunity to decide, do they change their mind?

    “It is worth noting that nearly three-quarters of reversible refusers thought they had originally agreed to receive secondary genomic findings,” said Will Schupmann, a doctoral candidate at UCLA and first author on the study. “This means that we should be skeptical about whether checkbox choices are accurately capturing people’s preferences.”

    Based on the results, the researchers question whether healthcare providers should ask people who have their genome sequenced if they want to receive clinically important secondary genomic findings. Investigators argue that enough data supports a default practice of returning secondary genomic findings without first asking participants if they would like to receive them.

    But research studies should create a system that also allows people who do not want to know their secondary genomic findings to opt out. The researchers suggest that if healthcare providers actively seek their patients’ preferences to know or not know about their secondary genomic findings, the providers should give the individuals multiple opportunities to make and revise their choice.

    “The right not to know has been a contentious topic in the genomics research community, but we believe that our real-world data can help move the field towards a new policy consensus,” said Berkman.

    Researchers at the NIH Department of Bioethics, NIEHS, Harvard University and Social & Scientific Systems collaborated on the study.

  • Male Hormones Regulate Stomach Inflammation in Mice

    Male Hormones Regulate Stomach Inflammation in Mice

    Scientists at the National Institutes of Health determined that stomach inflammation is regulated differently in male and female mice after finding that androgens, or male sex hormones, play a critical role in preventing inflammation in the stomach. The finding suggests that physicians could consider treating male patients with stomach inflammation differently than female patients with the same condition. The study was published in Gastroenterology.

    Researchers at NIH’s National Institute of Environmental Health Sciences (NIEHS) made the discovery after removing adrenal glands from mice of both sexes. Adrenal glands produce glucocorticoids, hormones that have several functions, one of them being suppressing inflammation. With no glucocorticoids, the female mice soon developed stomach inflammation. The males did not. However, after removing androgens from the males, they exhibited the same stomach inflammation seen in the females.

    “The fact that androgens are regulating inflammation is a novel idea,” said co-corresponding author John Cidlowski, Ph.D., deputy chief of the NIEHS Laboratory of Signal Transduction and head of the Molecular Endocrinology Group. “Along with glucocorticoids, androgens offer a new way to control immune function in humans.”

    While this study provides insight into how inflammation is being regulated in males, Cidlowski said additional research is underway to understand the process in females. The scientist handling this phase of research is co-corresponding author Jonathan Busada, Ph.D., assistant professor at West Virginia University School of Medicine in Morgantown. When Busada started the project several years ago, he was a postdoctoral fellow working in Cidlowski’s group.

    Whether inflammation is inside the stomach or elsewhere in the body, Busada said rates of chronic inflammatory and autoimmune diseases vary depending on sex. He said eight out of 10 individuals with autoimmune disease are women, and his long-term goal is to figure out how glucocorticoids and androgens affect stomach cancer, which is induced by chronic inflammation.

    The current research focused on stomach glands called pits, which are embedded in the lining of the stomach.

    Busada said the study showed that glucocorticoids and androgens act like brake pedals on the immune system and are essential for regulating stomach inflammation. In his analogy, glucocorticoids are the primary brakes and androgens are the emergency brakes.

    “Females only have one layer of protection, so if you remove glucocorticoids, they develop stomach inflammation and a pre-cancerous condition in the stomach called spasmolytic polypeptide-expressing metaplasia (SPEM),” Busada said. “Males have redundancy built in, so if something cuts the glucocorticoid brake line, it is okay, because the androgens can pick up the slack.”

    The research also offered a possible mechanism — or biological process — behind this phenomenon. In healthy stomach glands, the presence of glucocorticoids and androgens inhibit special immune cells called type 2 innate lymphoid cells (ILC2s). But in diseased stomach glands, the hormones are missing. As a result, ILC2s may act like a fire alarm, directing other immune cells called macrophages to promote inflammation and damage gastric glands leading to SPEM and ultimately cancer.

    “ILC2s are the only immune cells that contain androgen receptors and could be a potential therapeutic target,” Cidlowski said.


    This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research. To learn more about basic research, visit Basic Research – Digital Media Kit.


    Grant Numbers: 
    ZIAES090057 
    Fi2GM123974 
    P20GM103434 
    P20GM121322 
    U54GM104942 
    P30GM103488


    Reference:

    Busada JT, Peterson KN, Khadka S, Xu, X, Oakley RH, Cook DN, Cidlowski JA. 2021. Glucocorticoids and androgens protect from gastric metaplasia by suppressing group 2 innate lymphoid cell activation. Gastroenterology: doi: 10.1053/j.gastro.2021.04.075 [Online 7 May 2021].


  • Oregon State Researchers Discover New Class of Cancer Fighting Compounds

    Oregon State Researchers Discover New Class of Cancer Fighting Compounds

    CORVALLIS, Ore. – A team of Oregon State University scientists has discovered a new class of anti-cancer compounds that effectively kill liver and breast cancer cells.

    The findings, recently published in the journal Apoptosis, describe the discovery and characterization of compounds, designated as Select Modulators of AhR-regulated Transcription (SMAhRTs).

    Edmond Francis O’Donnell III and a team of OSU researchers conducted the research in the laboratory of Siva Kolluri, a professor of cancer research at Oregon State. They also identified the aryl hydrocarbon receptor (AhR) as a new molecular target for development of cancer therapeutics.

    “Our research identified a therapeutic lead that acts through a new molecular target for treatment of certain cancers,” Kolluri said.

    O’Donnell added: “This is an exciting development which lays a foundation for a new class of anti-cancer therapeutics acting through the AhR.”

    The researchers employed two molecular screening techniques to discover potential SMAhRTs and identified a molecule – known as CGS-15943 – that activates AhR signaling and kills liver and breast cancer cells.

    Specifically, they studied cells from human hepatocellular carcinoma, a common type of liver cancer, and cells from triple negative breast cancer, which account for about 15% of breast cancers with the worst prognosis.

    “We focused on these two types of cancers because they are difficult to treat and have limited treatment options,” said Kolluri, a professor in the Department of Environmental and Molecular Toxicology in the College of Agricultural Sciences. “We were encouraged by the results because they are unrelated cancers and targeting the AhR was effective in inducing death of both of these distinct cancers.”

    The researchers also identified the AhR-mediated pathways that contribute to the anti-cancer actions of CGS-15943. Developing cancer treatments requires a detailed understanding of how they act to induce anti-cancer effects. The researchers determined that CGS-15943 increases the expression of a protein called Fas Ligand through the AhR and causes cancer cell death.

    These results provide exciting new leads for drug development, but human therapies based on these results may not be available to patients for 10 years, the researchers said.

    An editorial commemorating the 25th anniversary issue of the journal Apoptosis highlighted this discovery and the detailed investigation of cancer cell death promoted by CGS-15943.

    In addition to Kolluri and O’Donnell, who recently completed medical school and is an orthopaedic surgery resident at UC Davis Medical Center, other authors of the paper are: Hyo Sang Jang and Nancy Kerkvliet, both from Oregon State; and Daniel Liefwalker, who formerly worked in Kolluri’s lab and is now at Oregon Health and Science University. Kolluri is also part of Oregon State’s Linus Pauling Institute and The Pacific Northwest Center for Translational Environmental Health Research.

    Funding for the research came from the American Cancer Society, National Institute of Environmental Health Sciences, the U.S. Army Medical Research and Material Command, the Department of Defense Breast Cancer Research Program, Oregon State University and the National Cancer Institute.