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Federally Funded Research: Making a Difference

Scientists that belong to FASEB member societies conduct impactful research that truly makes a difference in improving human health, as the following examples demonstrate. This research is funded by federal agencies including the National Institutes of Health (NIH), National Science Foundation (NSF), and the United States Department of Agriculture (USDA), Agriculture and Food Research Initiative (AFRI).

American Physiological Society (APS)

Funding Agency: NIH

Human ‘mini-guts’ enhance understanding of intestinal disease: Traditional methods of studying intestinal disease in the lab have relied on cells grown in culture, or animal models. However, both systems are limited in being able to adequately model human intestinal physiology. Researchers at the Johns Hopkins University School of Medicine have developed new methods of growing “mini-guts” in the lab using tissue from patient biopsies. These mini-guts include multiple cell types and more accurately mimic the normal physiology of the human gut. They can be used to test potential treatments for a variety of diseases, and yield insights into how disease-causing organisms interact with the gut’s immune system.1,2


American Society for Biochemistry and Molecular Biology (ASBMB)

Funding Agency: NSF, NIH

Plants provide insights for fatal disease: Lafora disease (LD) is a congenital, neurodegenerative epilepsy that impacts seemingly healthy teenagers in their prime. Over the course of a decade, patients develop increasingly severe and frequent seizures, hallucinations, dementia, and finally death. Discoveries funded by the National Science Foundation on how plants convert sunlight into the energy storage molecule starch provided insights to uncovering the molecular cause of LD.

Researchers at the University of Kentucky College of Medicine discovered and defined the molecular action of a class of enzymes necessary for plants to release the energy from starch to power cellular events and plant growth.  They found that mutations in a similar enzyme in humans are the cause of LD.  Recently these researchers and their collaborators uncovered multiple putative treatments for LD that they are testing in LD mouse models as part of the NIH--funded Lafora Epilepsy Cure Initiative.5


American Society of Pharmacology and Experimental Therapeutics (ASPET)

Funding Agency: NIH

“Biased” opiate drugs may lead to safer pain relief: The rapid increase in opiate prescribing for chronic pain since the mid-1990s has led to a marked increase in opiate-drug-related deaths. Over time, patients were taking larger doses of drugs to relieve their pain, but became susceptible to severe respiratory depression and death from opiate overdose. When prescribers began cutting back on opiate prescriptions, many patients with untreated pain turned to illegal opiates, further increasing their overdose risk.

A series of studies, including the work of researchers at the Scripps Research Institute and the University of California, Irvine, demonstrated that the analgesic and respiratory depressant actions of opiates were mediated by different signaling pathways, and that analogs of opiate drugs could be synthesized that activated only the “analgesia” pathway. The selective activation of one signaling pathway when more than one can be activated via a receptor is known as “biased agonism.” Companies in the private sector have now developed biased agonist drugs for the treatment of pain. These drugs will soon be approved by the Food and Drug Administration (FDA) as safer opiates for pain relief.6,7


American Society for Investigative Pathology (ASIP)

Funding Agency: NIH

Harnessing Genomic Tools to Treat Fibrosis: Characterized by a build-up of excess rigid, thick scar tissue, fibrotic diseases cause significant damage to organs and tissues and are one of the largest groups of disorders with no effective medical therapy.

One in particular, scleroderma, is an autoimmune disease with excessive inflammation causing skin damage and scarring. In progressive or severe forms of scleroderma, tissue damage can move into other organs such as the brain, kidneys, liver, lungs and heart. While the average 10-year survival rate has risen to 70 to 80 percent, disease consequences vary significantly among patients, and clinicians are unable to make early predictions about which patients will develop significant fibrosis.

Researchers at the University of Pittsburgh are using genomic technologies to identify correlations between scleroderma patients’ genomic profiles, symptoms, and clinical assessments. This research will support the development of personalized interventions that might slow the progression or decrease the severity of scleroderma and other fibrotic diseases.8


American Society for Nutrition (ASN)

Funding Agency: USDA Agriculture and Food Research Initiative

Food, Health & Choices Curriculum and Wellness Policy Intervention: As the rates of childhood obesity increase, important questions remain about how nutrition education curricula and wellness policy implementation change students’ eating and physical activity habits. In particular, there has been little research to compare school curriculum and wellness policy individually versus when both are implemented together.

Researchers at Columbia University are testing the effectiveness of these two interventions, alone and combined: a wellness policy that includes a classroom snack policy and physical activity breaks provided in classrooms during the school day; and a classroom curriculum comprised of 23 lessons that teach nutrition concepts through inquiry-based science explorations. Students who received the combined intervention consumed fewer sugar-sweetened foods and beverages, and were less likely to be considered overweight or obese compared with the control. Results of these studies have therefore begun to provide valuable information for educators in improving student health.9


American Association of Immunologists (AAI)

Funding Agency: NIH

Harnessing the immune system to fight cancer: Immunotherapy uses a person’s own immune system to fight disease and is revolutionizing the treatment of cancer. Major advances were made this year in a type of immunotherapy that uses genetically engineered immune cells. The FDA approved two chimeric antigen receptor (CAR) T-cell therapies – including one initially developed at NIH – for leukemia and lymphoma, marking the first gene therapy available in the U.S.10,11

Advances were also made in checkpoint inhibitors, a type of immunotherapy that blocks inhibitory receptors on immune cells to enhance the ability of the immune system to destroy cancer cells. NIH-funded basic researchers identified these receptors, which contributed to the development of checkpoint inhibitor drugs approved by the FDA to treat several cancer types, including melanoma, lung, kidney, bladder, stomach, and liver cancer.12,13 In May 2017, a checkpoint inhibitor was approved for solid tumors that have a specific genetic characteristic, which is the first FDA approval that relies on a genetic feature rather than on the tissue or site of the cancer.14


Society for Developmental Biology (SDB)

Funding Agency: NSF

Zebrafish help us understand how the nervous system develops: An animal’s nervous system is an elaborate communications network that performs numerous essential functions, including sensing and responding to the environment and regulating metabolism. As an animal embryo develops, nerve cells known as neurons must be configured and connected correctly in order to make a functional nervous system.

But fundamental questions remain as to how this process takes place during development. For a deeper understanding, researchers at the University of Chicago are studying how a single “pioneer” neuron can guide the movement of other neurons to their proper locations. By using the transparent embryos and larvae of zebrafish, the researchers will be able to follow this process by using and developing cutting-edge imaging and computational techniques for the study of cell movement.15


The Teratology Society (TS)

Funding Agency: NIH

Assessing the prevalence of Fetal Alcohol Syndrome: Fetal Alcohol Spectrum Disorders (FASD) are preventable, life-long disabilities, but accurate estimates of their prevalence have been lacking. Now, researchers at the University of California-San Diego, the University North Carolina-Chapel Hill, and the University of New Mexico undertook an extensive study to better estimate the rate of FASD in the U.S. They discovered a much higher prevalence of FASD than previously reported, as high as 3-10 percent of children. These results are a first step towards understanding the true burden of FASD in the U.S. and what might be done to prevent and treat these disorders.16


Endocrine Society (ES)

Funding Agency: NIH

Links between endocrine-disrupting chemicals and autism: Autism spectrum disorders (ASD) are developmental disorders that can severely impair communication and social interactions. ASD can cause distress for patients and their families, and is a source of significant strain on the U.S. health care system. ASD are thought to be caused by both genetic and environmental factors, and research is needed to better understand how these factors might be treated through prevention strategies and therapeutic interventions.  

Endocrine-disrupting chemicals (EDCs) are chemicals that can interfere with any aspect of hormone action, and they have well-documented effects on brain development in pediatric populations. NIH-funded investigators at the Icahn School of Medicine at Mount Sinai are studying exposure before birth to five classes of EDCs as potential environmental triggers for ASD. This information will help us better understand how our environment contributes to ASD and other diseases.17


International Society for Computational Biology (ISCB)

Funding Agency: NSF

Large-scale protein functional annotation: Using new sequencing technologies, scientists continue to generate large amounts of genomic data as they seek to understand the genetic basis for many biological processes. However, uncovering the biological relevance of these data presents a massive challenge. As the amount of genomic data from a diverse range of species continues to increase, computational methods for predicting function have become essential.

But until recently little was known about how well these methods perform. By competitively challenging over 60 research groups worldwide to develop and share their best software for function prediction, the Critical Assessment of Function Annotation project, or CAFA, drives the improvement of methods and thus the ability to more accurately explore and understand the vast complexity of biological systems. CAFA is led by a team of researchers from Iowa State University, Indiana University, University of Washington, University of Pennsylvania, and the European Bioinformatics Institute.18


Society for Glycobiology (SfG)

Funding Agency: NIH

Glycosylation inhibitor selectively kills lung cancer cells: Glycosylation, the process by which sugar molecules are added to proteins, is an essential cellular activity. Researchers have sought ways to block glycosylation in cancer cells in order to kill them without disrupting the function of normal, healthy cells. Now, Yale School of Medicine researchers and their colleagues from around the country have identified a small molecule glycosylation inhibitor, NGI-1, that reduces the growth of non-small cell lung cancer cells while having little impact on normal cells. The identification of this inhibitor will allow investigators to more fully understand the role of glycosylation in protein function generally, and may provide a unique therapeutic approach for cancers that rely on similar molecular mechanisms. In addition, NGI-1 has also been shown to inhibit dengue, Zika, West Nile, and yellow fever virus infections.19,20,21


Society for Redox Biology and Medicine (SfRBM)

Funding Agency: NIH

Towards new therapies for pulmonary hypertension: Recent work has begun to uncover the molecular basis for pulmonary hypertension, a type of high blood pressure that affects the arteries of the lungs and heart. In particular, there is evidence that a key antioxidant enzyme, EC-SOD, may provide protection from vascular inflammation caused by the presence of reactive oxygen molecules. Researchers at the University of Colorado-Denver are studying the molecular biology of this enzyme to better understand the mechanisms by which it might protect vascular tissue. Ultimately, this line of research may serve as the basis for novel, targeted antioxidant therapies for a wide range of serious lung diseases.22


Citations

1Baetz, et al. (2017). A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions.

2In, et al. (2016) Human mini-guts: new insights into intestinal physiology and host-pathogen interactions.

3Tagliabracci, V.S. and P.J. Roach. (2010) Insights into the mechanism of polysaccharide dephosphorylation by a glucan phosphatase.

4https://uknow.uky.edu/research/biomedical/uk-researchers-solve-metabolic-mystery-lending-insight-lafora-disease

5http://www.asbmb.org/asbmbtoday/201705/Feature/Lafora/

6Wadman, M  (2017)“Biased” opioids could yield safer pain relief.

7Stahl, EL et al. (2015) A novel method for analyzing extremely biased agonism at G protein-coupled receptors.

8Yates, C.C. Genomics of variability in progression and severity of skin fibrosis (NIH Project Number: 5R01AR068317-02)

9http://www.tc.columbia.edu/tisch/research-overview/nutrition-education/

10https://www.cancer.gov/news-events/cancer-currents-blog/2017/yescarta-fda-lymphoma

11https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm

12Chen, L. and Han, X. (2015) Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future.

13https://www.cancer.gov/about-cancer/treatment/drugs

14https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm560040.htm

15The roles of pioneer neurons and adhesion molecules in neuronal migration (NSF Award Abstract #1555972)

16https://betterbeginnings.org/news-press/jama-fasd-2018/

17Reichenberg , A. Autism and prenatal endocrine disruptors (NIH Project Number: 5R01ES026904-02)

18Bilateral BBSRC-NSF/BIO Collaborative Research: ABI Development: A Critical Assessment of Protein Function Annotation (NSF Award Abstract #1458359)

19Lopez-Sambrooks, C. et al. (2016) Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells

20Science Daily (2016). Chemical inhibitor may provide lung cancer treatment

21Puschnik, A.S. et al. (2017) A Small-Molecule Oligosaccharyltransferase Inhibitor with Pan-flaviviral Activity

22Grayck, E. N. Impact of insufficient vascular EC-SOD in pulmonary hypertension (NIH Project Number: 5R01HL086680-10)