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Study suggests ways to simplify health insurance enrollment​​​​​​​​​​

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E. Holland Durando

​​Enrolling in a health insurance plan can be confusing, especially for the previously uninsured. A new study, led by Washington University in St. Louis, looked at how plain language, graphics and stories​ can ease the enrollment process.

​The federal health-care law has reduced the number of uninsured people by about 10 million. But challenges remain, including how to educate new enrollees about their coverage options.

New research shows that communicating new, sometimes confusing information about the Affordable Care Act can be as simple as using plain language, providing comparisons to familiar contexts and using stories about how people might make health insurance decisions.

The study, led by Washington University in St. Louis, is one of the first to examine effective ways to explain key insurance terms and details to people who never have had health insurance. The research is now available online​ in the journal Medical Decision Making.

“Much of the insurance information that people receive is confusing, whether they’re enrolling in a plan under the Affordable Care Act or through an employer,” said first author Mary Politi, PhD, an assistant professor of surgery at the School of Medicine. “Anything we can do to ease the enrollment process benefits patients and their families — and simple solutions exist.”

The study’s 343 participants, from urban, suburban and rural areas, did not have health insurance previously or only recently had enrolled. They were randomly divided into three groups that saw plain-language tables alone, graphics that allowed participants to choose what information to see and in what order, or plain-language tables and stories about how other people make insurance decisions.

The researchers assessed knowledge about key terms such as "co-insurance," "deductible," "out-of-pocket maximum" and "formulary." (The latter is a list of medications that are approved under a health insurance policy.)

Politi

Researchers also determined the participants’ confidence in choices they made. The plain language tables, graphics and stories all worked to help people make choices that were consistent with their stated preferences. For example, those primarily interested in low premiums or low copayments for medications selected plans with those features.

The study did find that getting the uninsured or newly insured up to speed can be as easy as using:

  • ​Plain language in side-by-side comparisons of available insurance plans. An example is noting that deductibles work the same way with health insurance as they do with auto insurance.
  • Graphics that allow enrollees to review individual plan benefits they’re more likely to use. An example is a depiction of how each plan differs in regards to medication costs.
  • Stories about how people might make decisions about health insurance, using plain language to take them through the steps of comparing plans and enrolling.

“People found all three methods very helpful,” said senior author Timothy McBride, PhD, professor at the Brown School. “And they’re helpful for people across all levels of health literacy.”

The study also highlights the benefits of user-friendly formats – for example, presenting plan benefits in order of importance to enrollees rather than alphabetically, which is more typical.

Politi said the findings are useful for insurance companies, doctors' offices, hospitals, medical schools and other entities involving health insurance users.

“We should start by making sure enrollment materials are available and accessible to everyone,” she said. “Then we can provide more details to people who want more. Starting with simple information is never a bad thing for people making complex decisions about health insurance.”

Saint Louis University also participated in the research.


This work was supported by the Agency for Healthcare Research and Quality, grant R21HS020309.

Politi MC, Kaphingst KA, Liu J, Perkins H, Furtado K, Kreuter M, Shacham E, McBride T. A randomized trial examining three strategies for supporting health insurance decisions among the uninsured. Medical Decision Making, published online April 1, 2015.​

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.




McCaskill holds roundtable discussion on aging at Washington University

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Joe Angeles/WUSTL Photos

Sen. Claire McCaskill, D-Mo., held a roundtable discussion with experts on retirement security, elder justice and healthy aging March 31 at the Brown School’s Goldfarb Hall. Among the seven Washington University representatives on the panel was Chancellor Mark S. Wrighton.

As part of her series of Senior Listening Sessions across Missouri, Sen. Claire McCaskill held a roundtable discussion with experts on retirement security, elder justice and healthy aging March 31 at the Brown School’s Goldfarb Hall.

Among the roundtable participants were seven from Washington University in St. Louis. They were: 

  • Chancellor Mark S. Wrighton; 
  • Carolyn M. Baum, PhD, professor and the Elias Michael Executive Director of the Program in Occupational Therapy;
  • Christopher R. Carpenter, MD, associate professor and director of Evidence Based Medicine in the Division of Emergency Medicine; 
  • David B. Carr, MD, the Alan A. and Edith L. Wolff Professor of Geriatric Medicine and clinical director of the Division of Geriatrics and Nutritional Science;
  • Randy Larsen, PhD, the William R. Stuckenberg Professor of Human Values and Moral Development and professor of psychology in Arts & Sciences;
  • John C. Morris, MD, the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology and director and principal investigator of the Charles F. and Joanne Knight Alzheimer's Disease Research Center; and
  • Nancy Morrow-Howell, PhD, the Bettie Bofinger Brown Distinguished Professor of Social Policy at the Brown School and director of the Harvey A. Friedman Center for Aging, part of the Institute for Public Health.

The other institutions represented at the roundtable were Saint Louis University; the University of Missouri-St. Louis; the Mid-East Area Agency on Aging; the St. Louis Area Agency on Aging; AARP; Lutheran Senior Services; and the OASIS Institute.

“It was very exciting and energizing to host Sen. McCaskill,” said Morrow-Howell, who also is the faculty director of productive aging research at the Center for Social Development. “In her lead role on the Senate Special Committee on Aging, she can gain so much from the expertise we have here in the St. Louis area. 

“I was struck by all the knowledge and experience brought to this briefing by the aging experts from all around Washington University, as well as our institutional and community partners,” Morrow-Howell said.

To view the roundtable discussion, visit the Brown School media site



Medical Campus students perform 10th annual musical April 16-18

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You might think the demands of medical school would leave little time for extracurricular activities, yet every year for the past decade, students on the Medical Campus have produced, directed and starred in a musical.

This year, students will present “How to Succeed in Business Without Really Trying” at 8 p.m April 16, 17 and 18 in the Olin Residence Hall Gym on the Medical Campus.

The musical, which is entirely student-run, involves some 50 medical, occupational therapy, audiology, and biology and biomedical PhD students.

Tickets for students are $8 in advance or $12 at the door. General admission is $13 in advance or $16 at the door. Tickets are available now and can be purchased from noon to 1:30 p.m. weekdays in the Farrell Learning and Teaching Center atrium, or they can be reserved by emailing Runjun Kumar at kumarr@wusm.wustl.edu

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Photos by Tim Parker

Cast members of "How to Succeed in Business Without Really Trying," the 10th annual musical presented by students on the Medical Campus, rehearse in the Olin Residence Hall Gym. The musical will be performed April 16, 17 and 18.

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New Ebola study points to potential drug target

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Amarasinghe lab

A protein — shown in red, white and blue — typically coats the genome of the Ebola virus, providing protection from enzymes that can destroy the virus's genetic material. This protein coat is removed to allow the virus to replicate its genome in infected cells. New research led by Washington University School of Medicine shows that interfering with the removal and the return of the protein coat to the viral genome can kill the Ebola virus, a discovery that opens the door to more effective treatments.



Opening the door to potential treatments for the deadly Ebola virus, scientists have found that a protein made by the virus plays a role similar to that of a coat-check attendant. 

The protein removes a protective coat from the virus’s genetic material, exposing the viral genome so that it can be copied, and then returns the coat, according to a new study led by scientists at Washington University School of Medicine in St. Louis.

The research, in cell cultures, showed that interfering with this process kills the virus.

As part of the study, the researchers introduced rogue coat-check attendants into Ebola-infected cells. These rogue attendants carried a short chain of amino acids that forms the part of the protein that removes the coat. But they lacked the ability to return the coat, disrupting the emergence of newly created viruses from infected cells. Consequently, the virus did not survive.

“This coat-check protein, known as VP35, has a great deal of potential as a new target for Ebola treatments,” said senior author Gaya Amarasinghe, PhD, assistant professor of pathology and immunology at the School of Medicine. “If we can block this process, we can stop Ebola infection by blocking viral replication.”

The study appears April 9 in Cell Reports.

The Ebola outbreak that began last year in West Africa has infected nearly 25,000 people and killed more than 10,000, according to the Centers for Disease Control and Prevention.

Ebola and other viruses like it are made of a single strand of RNA, a genetic material closely related to DNA. Higher organisms use RNA to copy protein-building instructions from their DNA, but Ebola stores such instructions — the virus’s genetic self — directly in RNA.

RNA is less stable than DNA and can set off immune defenses that destroy viruses. So Ebola keeps its RNA covered with a protective coat called the nucleoprotein.

To replicate, however, the virus has to partially remove the nucleoprotein and expose its RNA to the viral copying machinery. Amarasinghe and first author Daisy Leung, PhD, together with colleagues at the Icahn School of Medicine at Mount Sinai, University of Texas Southwestern Medical Center, Texas Biomedical Research Institute and Baylor University, have spent the past seven years studying the role of VP35, a viral protein involved in the replication process,

“One of the major challenges was that the part of VP35 involved in this interaction is an intrinsically disordered peptide,” said Leung, an assistant professor of pathology and immunology at Washington University. “This means that it may not take on a definite structure until it binds to another protein. That made structural studies of VP35 difficult because the structure, which plays a critical role in determining function, doesn't form without its specific binding partner.”

The researchers showed that VP35 binds to the virus’s nucleoprotein — which forms part of the protective coat worn by the virus’ RNA. They found that this binding removes the nucleoprotein from the viral RNA prior to replication. And while the viral RNA is being copied, VP35 keeps newly synthesized nucleoproteins from attaching to other RNA in the host cell.

New copies of the virus require new protein coats. So VP35 also ensures that new nucleoproteins — made by the host cell’s protein-making machinery — bind only to Ebola RNA, allowing the virus to complete replicating. Disabling or disrupting VP35 could stop the virus in its tracks, according to Amarasinghe.


The research was supported by the U.S. Department of Defense, grants DTRA 1-21-1-0002, DTRA-HDTRA1-12-1-0051, DTRA HDTRA1-14-1-0013; the National Institutes of Health (NIH), grants R01AI107056, R01GM053163, R01AI077519, R01AI059536, U19AI109945, U19AI109664, U19AI070489, P41GM103832, P50 GM1003297, R01Ai081914; the National Institute of General Medical Sciences, grant P41GM103399; and the Center for Structural Genomics of Infectious Diseases, contract number HHSN272201200026.

Leung DW, Borek DM, Luthra P, Binning JM, Anantpadma M, Liu G, Harvey IB, Su Z, Endlich-Frazier A, Pan J, Shabman RS, Chiu W, Davey R, Otwinowski Z, Basler CF, Amarasinghe GK. An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions. Cell Reports, April 9, 2015.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.



Corbo receives research grants

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Joseph Corbo, PhD, MD, associate professor of pathology and immunology, of genetics, and of ophthalmology and visual sciences at Washington University School of Medicine in St. Louis, has received a one-year, $40,000 grant from the McDonnell Center for Cellular and Molecular Neurobiology for research titled “Supercharging Optogenetic Devices by Red-Shifted Chromophore Substitution,” and a $15,000 grant from the Washington University Intellectual and Developmental Disabilities Research Center for research titled “Elucidating the Role of Non-Coding Variation in Intellectual Disability Disorders."



Feibel named director of Center for History of Medicine

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Feibel

Robert M. Feibel, MD, has been named director of the Center for History of Medicine at Washington University School of Medicine. The center is housed on the sixth floor of the Bernard Becker Medical Library.

Feibel, professor of clinical ophthalmology and visual sciences, teaches and supervises residents in the eye clinic at Barnes-Jewish Hospital. He has published extensively on the topic of ophthalmology history.

Feibel succeeds Thomas Woolsey, MD, professor emeritus of neurological surgery. The inaugural director of the center, Woolsey retired late last year.



Bear Cub Challenge faculty awardees announced

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Following a four-month rigorous training and selection process involving 46 exceptional applications to the 2015 Bear Cub Challenge at Washington University in St. Louis, grants have been awarded to the top  applicants.

The university’s Bear Cub grant program helps researchers make the leap from bench scientists to budding entrepreneurs. The program funds promising translational research – not normally backed by federal grants – that is critical to demonstrating a technology’s commercial potential.

The newest Bear Cub grant recipients are the:

  • "Recombinant Hemoglobin Sourcing to Enable Scale-Up for Novel Blood Substitute" team, led by Allan Doctor, MD, professor of pediatrics and associate professor of biochemistry and molecular biophysics at the School of Medicine; and
  • "A Fast, Accurate Hearing Test" team, led by Dennis Barbour, MD, PhD, associate professor of biomedical engineering in the School of Engineering & Applied Science.
Doctor

The Bear Cub program will provide the two projects with up to $75,000 each, as teams work toward their goals of commercial licensing and developing products that will attract investors.

Additionally, five other finalists will be provided with cash and in-kind services valued at up to $150,000.

Providing support to the teams are the Skandalaris Center for Interdisciplinary Innovation and Entrepreneurship; the Center for Research Innovation in Business (CRIB); the Office of Technology Management (OTM); and the BioGenerator.

Among the services provided are: Small Business Innovation Research (SBIR) and Small Business Technology Transfer grant application preparation; help developing business plans and pitch decks to enable private capital investment; and intellectual property assessment as well as due diligence by top national industry and venture capital leaders in respective fields.

Barbour

“The Bear Cub Challenge reflects Washington University’s commitment to facilitate the practical application of scientific discoveries,” said Provost Holden Thorp, PhD. “All 46 Bear Cub participants have advanced their projects and learned a great deal. Our innovation and entrepreneurship team is looking forward to continuing to mentor current and future applicants to maximize the impact of our university’s outstanding research.”

In past years, Bear Cub grants have funded an array of projects, including the development of a new treatment for pancreatic cancer, a diagnostic test for acute kidney damage, and a photonic switch to help make ultra-high speed Internet access a reality.

To enable broader participation, the Bear Cub Challenge has moved from a yearly cycle to once every four months. Finals for the next cycle of the challenge will take place in September, with educational and training sessions commencing in early May.

Interested individuals are encouraged to contact the Skandalaris Center, the OTM or the CRIB.

Gidday receives $1M-plus NIH glaucoma research grant

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Gidday

Jeff Gidday, PhD, associate professor of neurosurgery, of ophthalmology and visual sciences, and of cell biology and physiology at Washington University School of Medicine in St. Louis, has received a four-year, $1.4 million grant from the National Institutes of Health (NIH) for research titled “Endogenous Neuroprotection in Glaucoma.”




Researcher Burgers receives $2M NIH grant for DNA research

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Burgers

Peter M. Burgers, PhD, the Marvin A. Brennecke Professor of Biological Chemistry at Washington University School of Medicine in St. Louis, has received a four-year, $2.04 million grant from the National Institute of General Medical Sciences of the National Institutes of Health (NIH) for research titled “Enzymology of Replication of Yeast Chromosomal DNA.” 

Further, Burgers and Amir Aharoni, PhD, of Ben-Gurion University of the Negev, have received a four-year $91,600 grant from the United States-Israel Binational Science Foundation for research titled “Switching of DNA Polymerases on the PCNA Ring during DNA Damage Response.”



Study finds 1.2 percent of preschoolers on Medicaid use psychotropic drugs

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A new study finds that that 1.2 percent of American preschool children on Medicaid are using psychotropic drugs, including antidepressants, mood stabilizers and medications for attention-deficit disorder.

Using 2000-2003 Medicaid Analytic Extract data from 36 states, a group of researchers at the Brown School at Washington University in St. Louis and at Washington University School of Medicine in St. Louis found preschoolers are receiving psychotropic medications despite limited evidence supporting safety or efficacy.

The results of the study are published in the March issue of the American Journal of Public Health.

“Because we don’t have indications in our data, it is not entirely clear why these children are receiving psychotropic drugs,” said Lauren Garfield, PhD, lead author on the study, who was a postdoctoral research associate at the Brown School when the study was conducted and is now with Mercy Research in St. Louis.

Raghavan

“It is possible that some of these children have brain injuries or insults, such as traumatic brain injuries, fetal alcohol syndrome or the like, for which treatment is being provided. But if these medications are being used solely for behavioral control, then it seems clear that we need to better assess these children, and see if they might be better served by the use of evidence-based behavioral interventions,” said Ramesh Raghavan, MD, PhD, co-author on the study, associate professor at the Brown School and associate professor of psychiatry at the School of Medicine.

Raghavan is currently on sabbatical from Washington University, serving at the Administration on Children and Families (ACF) in the U.S. Department of Health and Human Services in Washington.

The researchers followed children in two cohorts, born in 1999 and 2000, up to 4 years of age. They used logistic regression to model odds of receiving medications for attention-deficit disorder/attention-deficit hyperactivity disorder (ADHD), depression or anxiety and psychotic illness or bipolar.

Between 2000 and 2003, the researchers found that 1.19 percent of children received a prescription for any ADHD, depression or anxiety, or psychotic illness or bipolar medication. In addition, 0.17 percent of infants younger than 1 year old and 0.34 percent of children between 1 and 2 years were being prescribed psychotropic drugs.

Across ages and cohorts, 0.61 percent of children received a prescription for ADHD, 0.59 percent for depression or anxiety and 0.24 percent for psychotic illness or bipolar disorder.

“Although the absolute numbers and percentages of these drugs were small, these findings are worrying in so far as they indicate the use of psychotropic drugs among very young children,” the authors wrote in the study.

"The fact that any children this small are using psychotropic drugs is very worrisome," said Raghavan.

“The existing evidence base in the area of trauma-informed psychosocial interventions warrants a large initial investment to expand access to effective interventions,” said JooYeun Chang, associate commissioner of the Children’s Bureau at the ACF.

Chang is helping to lead the effort on the federal level to reduce unnecessary psychotropic medication use among child welfare populations.

“The ACF budget request for $250 million over five years would fund infrastructure and capacity building, while the Medicaid investment of $500 million over five years would provide incentive payments to states that demonstrate measured improvement,” she said. “This proposal presents a concerted effort to reduce over-prescription of psychotropic medications for these children by increasing the availability of evidence-based, psychosocial treatments that meet the complex needs of children who have experienced maltreatment. Increased access to timely and effective screening, assessment and non-pharmaceutical treatment will reduce over-prescription of psychotropic medication as a first-line treatment strategy, improve their emotional and behavioral health, and increase the likelihood that children in foster care will exit to positive, permanent settings, with the skills and resources they need to be successful in life.”

The study’s other authors are Derek S. Brown, PhD, assistant professor at the Brown School; Benjamin T. Allaire of Research Triangle Institute in North Carolina; and Raven E. Ross, a doctoral student at the Brown School.

The full study is available at ajph.aphapublications.org/doi/full/10.2105/AJPH.2014.302258.



Gene variant linked to smoking longer, getting lung cancer sooner

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Robert Boston
Researchers Laura Jean Bierut, MD (left), and Li-Shiun Chen, MD, examine X-rays of a patient with lung cancer. The two have found that smokers with a variation in a gene involved in processing nicotine are likely to keep smoking longer and develop cancer sooner than people who don't have the gene variant.


Smokers with a specific genetic variation are more likely to keep smoking longer than those who don’t have the gene variant, new research indicates. They’re also more likely to be diagnosed with lung cancer at a younger age.

Researchers at Washington University School of Medicine in St. Louis led an analysis of 24 studies involving more than 29,000 smokers of European ancestry and found that smokers with a particular variation in a nicotine receptor gene were more likely to continue smoking for four years after those without the variant had quit. Those with the genetic variant also were more likely to be diagnosed with lung cancer four years earlier than those without the variation in the CHRNA5 gene.

The findings may result in changes to efforts to screen patients for lung cancer. They are published April 14 in the Journal of the National Cancer Institute.

“People with the risk variant average a four-year delay in the age at which they quit smoking,” said first author Li-Shiun Chen, MD. “Instead of quitting at age 52, which was the average age when study participants with a normal gene stopped smoking, people with the genetic variant quit at age 56.”

Chen said those with the gene variant also tend to inhale more deeply when they smoke. That combination of genes and behavior contributes to the development of lung cancer earlier in life.

“They are likely to be diagnosed four years earlier,” she said. “In those with lung cancer, the average smoker without the gene variant is diagnosed at age 65. Those with the greater genetic risk tend to be diagnosed at 61.”

Chen said the presence of the gene variation has important clinical implications. Smokers who have the gene variant could undergo lung cancer screening at a younger age, she said. In addition, previous work from Chen and senior investigator Laura Jean Bierut, MD, shows that those with the gene variant are more likely to respond to medications that help people quit smoking, so knowing more about a smoker's genetic makeup could help guide that individual's therapy.

“The same people with this high-risk gene are more likely to respond to smoking-cessation medications, such as nicotine-replacement patches, lozenges or gum,” Chen said. “Although it’s clear the gene increases the chances a person will develop lung cancer at a younger age, it also is clear that the risk can be reversed with treatment.”

Lung cancer is the most common cancer worldwide, making up 13 percent of all cancer cases and leading to 27 percent of all cancer deaths. And survival rates are low. About half of all lung cancer patients die within a year of being diagnosed. Only about one in six are still alive five years after diagnosis.

“So a diagnosis that comes four years earlier is very significant clinically,” Chen explained.

Bierut, the Alumni Endowed Professor of Psychiatry at Washington University, said the clinical implications of the findings are enormous. Currently, people tend to be screened for lung cancer according to how much they smoke and how old they are. But the new research supports the idea of doctors using genetic information to target people who might not be screened otherwise, she explained.

“Adding this information to screening criteria could help us focus our resources on people at the highest risk,” Bierut said. “In addition, knowing that they are the ones most likely to respond to nicotine-replacement therapy could allow us to respond with treatments that are more likely to be effective.”

Chen and Bierut plan to expand their studies to include smokers from ethnic groups not represented in this analysis. They also want to look at other genes related to smoking, nicotine dependence and cancer risk, with the goal of creating a risk score that could be used to assess addiction and cancer risk in individual smokers.


This work was funded by the National Cancer Institute, the National Human Genome Research Institute, the National Institute on Drug Abuse, the National Heart, Lung and Blood Institute, and the National Center for Research Resources of the National Institutes of Health (NIH). Additional funding was provided by the COPD Foundation through contributions made to an industry advisory board comprised of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Siemens and Sunovion. NIH grant numbers U19-CA148127, P50-CA70907, R01-CA121197, R01-CA127219, R01-CA55769, CA074386, CA092824, CA090578, R01-DA038376, R01-DA036583, P30-CA091842, K07-CA160753, P01-CA089392, U01-HG04422-01, K02-DA021237. HHSN271200477471C, HHSN271200477451C, HHSN268200782096, KL2-RR024992, K08-DA030398, U01-HL089897, U01-HL089856, R01-CA55874, N01-CN05223, R01-CA60691, R01-CA14176, N01-PC35145, P30-CA022453, R01-80127/84354, P20-RR018787, R01-CA52689, 2P01-CA87969-11, U19-CA148065-01, U19-CA148127. For a full list of other funding agencies, please see the supplementary text section of the paper.

Chen LS, et al. CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis. Journal of the National Cancer Institute, published online April 14, 2015.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.




Medical students make music at spring Coffeehouse

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Photos By Robert Boston

The cleverly named a cappella group Do No Harmony, which was started by medical students who soon will graduate, performs Tuesday, April 7, at a Medical Campus Coffeehouse. The event, an opportunity for students on the Medical Campus to share their musical talents, was in the Farrell Learning and Teaching Center. 

 

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Second-year medical student Giuseppe D'Amelio (front) plays electric guitar  while band member Eryk Ocasio, a student in the Program in Physical Therapy, plays bass. 

 

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Fourth-year medical students Zach Meyer (left) and Allan Jiang perform a musical number at the Coffeehouse.

 

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Elizabeth Letvin, a second-year graduate student at the Brown School, plays viola as part of a quintet at the Coffeehouse. Her brother, medical student Adam Letvin, also plays in the quintet.

 

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Listeners gather in the Farrell Learning and Teaching Center on the Medical Campus to hear one of several Coffeehouse musical acts. 

 



Obituary: John W. Olney, 83, professor of psychiatry and neuropathology

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John W. Olney, MD, the John P. Feighner Professor of Psychiatry and a professor of pathology and immunology, died Tuesday, April 14, 2015, at his home in St. Louis after a battle with lung cancer and amyotrophic lateral sclerosis (ALS). He was 83.

Olney

A longtime leader in the Department of Psychiatry at Washington University School of Medicine in St. Louis, Olney remained active in research until the last few days of his life.

He studied neurotransmitters in the brain and how they can become toxic under certain circumstances. He was the first scientist to propose that when high concentrations of the neurotransmitter glutamate were released from brain cells, the glutamate could overexcite cellular receptors and destroy cells through a process he named “excitotoxicity.” The mechanism Olney described was later found to be involved in nerve cell degeneration in traumatic brain injury and brain disorders such as stroke and epilepsy.

“John was truly a unique individual who had an enormous impact in psychiatry and across many scientific and clinical disciplines,” said Charles F. Zorumski, MD, the Samuel B. Guze Professor, professor of neurobiology and head of the Department of Psychiatry. “He was an innovator and a pioneer. Literally, the field of studying glutamate as an excitotoxin, and even the word ‘excitotoxicity’ itself, can be traced to John’s seminal studies in the late 1960s and 1970s. And his most recent work on the effects of drugs on the developing brain has changed how pediatric anesthesia is done.”

Olney came to Washington University in 1964 as a resident in psychiatry and joined the faculty in 1968. He started his medical training at age 28, leaving a job in the U.S. Army to pursue a medical degree when his sister was diagnosed with multiple sclerosis. Born in Marathon, Iowa, Olney earned his bachelor’s and medical degrees from the University of Iowa.

In addition to working with glutamate, Olney studied the effects of anesthetic drugs, such as ketamine, on the developing brain. He did important and much-cited research into fetal alcohol syndrome, concluding that if a pregnant woman consumed as few as two drinks, the alcohol could cause nerve cells in the fetal brain to die. And Olney found that as the brain continued to develop in the years after a baby was born, anesthetic drugs also had the capacity to do damage. Consequently, he recommended that elective surgery be avoided in very young children whenever possible.

Olney was a member of the Institute of Medicine of the National Academy of Sciences. He was a recipient of the Wakeman Award for Research in the Neurosciences, the Dana Foundation Award for Achievement in Health and the Lifetime Achievement Award from the Society of Biological Psychiatry.

Olney is survived by Elfriede Olney, his wife of 57 years; two children, Margaret Ann Olney and John M. Olney; and six grandchildren. Another son, Stephen James Olney, passed away in 1984.

A funeral will be held Friday at Bopp Chapel, 10610 Manchester Road, in Kirkwood, Mo. Public visitation will be from 3-5 p.m., with the funeral beginning at 5 p.m. A memorial service at the School of Medicine will be held at a later date.

Memorial contributions may be made to the Washington University Thoracic Oncology Research Fund; 7425 Forsyth Blvd., Campus Box 1247; St. Louis, MO 63105.


Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.




Convenience, workplace incentives may increase use of public transit

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WUSTL Photos
Worksite policies can have an effect on employees' use of public transportation, a new study says.

Transit stops close to home and workplace incentives are associated with higher likelihood that commuters will choose public transportation, according to research from the Brown School at Washington University in St. Louis and Washington University School of Medicine in St. Louis.

Investigators interviewed 1,338 residents of four metropolitan areas in Missouri about their commuting habits. As previous studies had suggested, they found that nearly 90 percent drove to work, while 5 percent used public transportation and 6 percent walked or cycled.

Having transit stops within 10-15 minutes’ walking distance from home, and workplace incentives such as discounts for public transit were associated with its use, the study found. Having free or low-cost recreation facilities and places to lock bikes around worksites made it more likely that workers walked or cycled to their jobs.

“While changing the physical environment may be challenging, worksite policies such as incentives and safe bike storage are relatively easy and inexpensive to implement,” said lead author Lin Yang, PhD, postdoctoral research associate at the Division of Public Health Sciences at the School of Medicine.

The results were published in March in the Journal of Transport & Health.

Hipp

“Most public transit stops are not directly located at people’s home or work, so they get physical activity by walking out of the house to the bus stop, and then from the bus stop to work,” said study co-author Aaron Hipp, PhD, assistant professor at the Brown School. 

“I know that it takes me eight minutes to briskly walk from my office to the Metrolink stop," Hipp said. "I do this twice a day when I commute. My walk home is more like three minutes. So round trip, I am getting at least 22 minutes of activity I would not be by driving a personal car.”

Other authors on the study were Deepti Adlakha, a PhD-candidate at the Brown School; Christine Marx, project coordinator at the Division of Public Health Sciences; Rachel Tabak, PhD, research assistant professor at the Brown School; and Ross Brownson, PhD, the Bernard Becker Professor and PRC co-director.



Marshall receives grants, named visiting professor in Italy

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Garland Marshall, PhD, professor of biochemistry and molecular biophysics, in Washington University School of Medicine in St. Louis and of biomedical engineering, in the univeristy's School of Engineering & Applied Science, has received a $50,000 grant from the National Institute of General Medical Sciences of the National Institutes of Health (NIH) for research titled “Discovery of New Therapeutics for Drug-Free Remission of HIV”, and a $50,000 grant from Epigenetx LLC for research titled “Characterization of Lysine Deacetylase Inhibitors (KDACIs).”

Marshall also was named a visiting professor at Sapienza Università di Roma in Italy for the spring semester. He had a similar appointment in fall 2011. While there, his collaborations with professors in the university's School of Pharmacy led to NIH-supported research at Washington University.




Miller named Clayson Professor of Neurology

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Miller

Timothy M. Miller, MD, PhD, a leading researcher in the neurodegenerative disorder amyotrophic lateral sclerosis (ALS), has been named the David Clayson Professor of Neurology at Washington University School of Medicine in St. Louis.

The professorship was established in 2001 through a bequest from David Clayson, PhD, to support innovative research into treatments for ALS, the fatal paralyzing disorder also known as Lou Gehrig’s disease. Clayson, who graduated from the School of Medicine in 1963, died of ALS in 2001.

In ALS, the nerve cells that control muscles die, leading to gradual paralysis and death. Miller is investigating what causes these nerve cells to die and potential approaches for keeping them alive.

“Dr. Miller is doing very innovative work on a number of fronts in ALS research,” said Larry J. Shapiro, MD, executive vice chancellor for medical affairs and dean of the School of Medicine. “His studies — including a first-of-its-kind clinical trial of a new approach to ALS therapy — have produced intriguing results that made him an outstanding recipient for the Clayson professorship.”

Cutting-edge treatments under investigation in the Miller laboratory include microRNAs, small pieces of genetic material that can silence genes, possibly including the genes involved in ALS.

Miller and his colleagues have identified changes in microRNAs in a mouse model of ALS and in tissue samples from people with ALS, and are working to determine if the changes cause ALS and if they can be blocked, he explained.

“Dr. Miller excels at finding ways to apply the latest techniques for modifying biological systems to the challenges of treating ALS and other disorders that have long resisted our attempts to stop them,” said David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor of Neurology and head of the Department of Neurology.

Miller is the director of the Christopher Wells Hobler Laboratory for ALS Research at the Hope Center for Neurological Disorders at Washington University, a center dedicated to improving the lives of people with neurological disorders through research into the causes of and potential treatments for such disorders. The center is a collaboration between the university and Hope Happens, a St. Louis-based organization that promotes awareness, education and fundraising regarding research into neurological disorders.

Miller also is a scientific advisory and executive committee member of the Northeast ALS Consortium, a member of the American Academy of Neurology, the American Neurological Association and the Society for Neuroscience.

He earned his medical degree and PhD at the School of Medicine in 1998. He then trained as a neurology resident and neuromuscular fellow at the University of California, San Francisco, from 1998-2003. He next moved to the University of California, San Diego, where he spent four years as part of the Mentored Scientist Clinical Training Program there, doing postdoctoral work on disease models of ALS.

David Clayson

Clayson earned a bachelor’s degree in philosophy at the University of Utah in 1956, a master’s degree in clinical psychology at George Washington University in 1960, and his doctorate in clinical psychology at Washington University in St. Louis in 1963. He completed a predoctoral fellowship at Jefferson Barracks Veterans Administration (VA) Medical Center in St. Louis; interned at the VA Mental Hygiene Clinic in Washington; and was a postdoctoral fellow at the John Cochran VA Medical Center in St. Louis.

For 25 years, he was the head of psychology at the Payne Whitney Clinic at Weill Cornell Medical College. In 2001, he became the college’s first recipient of the Dean’s Award for Lifetime Achievement in Teaching.

Clayson co-founded what is now the Association of Psychologists in Academic Health Centers. He was a leading authority on psychological testing and also contributed to improved recognition of the significant psychological aspects of illness. 


Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.




Graduate students recognize faculty mentors

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Mary butkus/WUSTL Photos
Erin McGlothlin, PhD (right), associate professor of German and of Jewish studies in Arts & Sciences, received an Outstanding Faculty Mentor Award. She is pictured with one of her graduate students who nominated her for the award, Ervin Malakaj, a PhD-candidate in German.


Eight Washington University in St. Louis faculty were recognized with Outstanding Faculty Mentor Awards during the Graduate Student Senate’s 16th annual awards ceremony and reception April 9 in the Women’s Building Formal Lounge.

The 2014-15 Outstanding Faculty Mentor Award recipients are:

  • Christine Floss, PhD, professor of physics in Arts & Sciences;
  • Bret Gustafson, PhD
, associate professor of sociocultural anthropology in Arts & Sciences;
  • Tristram R. Kidder, PhD, professor of environmental studies in anthropology in Arts & Sciences;
  • Erin McGlothlin, PhD, associate professor of German and of Jewish studies in Arts & Sciences;
  • Melanie Micir, PhD, assistant professor of English in Arts & Sciences;
  • Shelly Sakiyama-Elbert, PhD
, professor of biomedical engineering;
  • James B. Skeath, PhD, professor of genetics in the Division of Biology and Biomedical Sciences at the School of Medicine; and
  • Abraham Z. Snyder, MD, PhD, research scientist in the Department of Radiology in the Division of Biology and Biomedical Sciences at the School of Medicine.
The awards are based on nominations by graduate students and designed to honor faculty members whose dedication to mentoring PhD students and commitment to excellence in graduate training have made a significant contribution to the quality of life and professional development of students in the Graduate School of Arts & Sciences.

McGlothlin is a two-time winner of the award, previously receiving it in 2007.

Special recognition for excellence in mentoring went to six other faculty members at the ceremony.

To see the list of the special recognition winners as well as bios and student comments on all the winners, visit the Graduate Student Senate site.

Bacterial flora of remote tribespeople carries antibiotic resistance genes

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Scientists have found antibiotic resistance genes in the bacterial flora of a South American tribe that never before had been exposed to antibiotic drugs. The findings suggest that bacteria in the human body have had the ability to resist antibiotics since long before such drugs were ever used to treat disease.

Oscar Noya-Alarcon
Huts in an isolated village inhabited by Yanomami Amerindians in a remote, mountainous area in southern Venezuela. Members of the tribe were isolated from the modern world and had never been exposed to antibiotic drugs, but the bacteria on their skin and in their mouths and intestines still had antibiotic resistance genes.

The research stems from the 2009 discovery of a tribe of Yanomami Amerindians in a remote mountainous area in southern Venezuela. Largely because the tribe had been isolated from other societies for more than 11,000 years, its members were found to have among the most diverse collections of bacteria recorded in humans. Within that plethora of bacteria, though, the researchers have identified genes wired to resist antibiotics.

The study, published April 17 in Science Advances, reports that the microbial populations on the skin and in the mouths and intestines of the Yanomami tribespeople were much more diverse than those found in people from the United States and Europe. The multicenter research was conducted by scientists at New York University School of Medicine, Washington University School of Medicine in St. Louis, the Venezuelan Institute of Scientific Research and other institutions.

“This was an ideal opportunity to study how the connections between microbes and humans evolve when free of modern society’s influences,” said Gautam Dantas, PhD, associate professor of pathology and immunology at Washington University and one of the study’s authors. “Such influences include international travel and exposure to antibiotics.”

Dantas

Intriguingly, in Dantas’ lab, graduate student Erica Pehrsson searched for and found antibiotic resistance genes in bacteria on the skin and in the mouths and intestines of tribe members long isolated from such outside influences.

“These people had no exposure to modern antibiotics; their only potential intake of antibiotics could be through the accidental ingestion of soil bacteria that make naturally occurring versions of these drugs,” Pehrsson said. “Yet we were able to identify several genes in bacteria from their fecal and oral samples that deactivate natural, semi-synthetic and synthetic drugs.”

Thousands of years before people began using antibiotics to fight infections, soil bacteria began producing natural antibiotics to kill competitors. Similarly, microbes evolved defenses to protect themselves from the antibiotics their bacterial competitors would make, likely by acquiring resistance genes from the producers themselves through a process known as horizontal gene transfer.

In recent years, the abundance of antibiotics in medicine and agriculture has accelerated this process, stimulating the development and spread of genes that help bacteria survive exposure to antibiotics. Consequently, strains of human disease that are much harder to treat have emerged.

“We have already run out of drugs to treat some types of multidrug-resistant infections, many of which can be lethal, raising the bleak prospect of a post-antibiotic era,” Dantas said.

Scientists don’t really know whether the diversity of specific bacteria improves or harms health, Dantas said, but added that the microbiomes of people in industrialized countries are about 40 percent less diverse than what was found in the tribespeople never exposed to antibiotics.

“Our results bolster a growing body of data suggesting a link between, on one hand, decreased bacterial diversity, industrialized diets and modern antibiotics, and on the other, immunological and metabolic diseases — such as obesity, asthma, allergies and diabetes, which have dramatically increased since the 1970s,” said Maria Dominguez-Bello, PhD, associate professor of medicine at New York University Langone Medical Center and senior author of the study. “We believe there is something occurring in the environment during the past 30 years that has been driving these diseases, and we think the microbiome could be involved.”

M. Gloria Dominguez-Bello
The study's senior author, M. Gloria Dominguez-Bello, PhD, of New York University Langone Medical Center (right), and co-author Oscar Noya-Alarcon, PhD, of the University of Central Venezuela, on the Amazon River in southern Venezuela.

Dominguez-Bello said the research suggests a link between modern antibiotics, diets in industrialized parts of the world and a greatly reduced diversity in the human microbiome — the trillions of bacteria that live in and on the body and that are increasingly being recognized as vital to good health.

The vast majority of human microbiome studies have focused on Western populations, so access to people unexposed to antibiotics and processed diets may shed light on how the human microbiome has changed in response to modern culture, and may point to therapies that can address disease-causing imbalances in the microbiome.

In the current study, when the researchers exposed cultured bacterial species from the tribe to 23 different antibiotics, the drugs were able to kill all of the bacteria. However, the scientists suspected that these susceptible bacteria might carry silent antibiotic resistance genes that could be activated upon exposure to antibiotics.

They tested for such activation, and the tests confirmed their suspicions. The bacterial samples contained many antibiotic resistance genes that can fend off many modern antibiotics. These genes may turn on in response to antibiotic exposure.

“However, we know that easily cultured bacteria represent less than 1 percent of the human microbiota, and we wanted to know more about potential resistance in the uncultured majority of microbes,” Dantas said.

So the researchers applied the same method, called functional metagenomics, to identify functional antibiotic resistance genes from Yanomami fecal and oral samples without any prior culturing. From that experiment they were able to identify nearly 30 additional resistance genes. Many of these genes deactivated natural antibiotics, but the scientists also found multiple genes that could resist semi-synthetic and synthetic antibiotics.

“These include, for example, third- and fourth-generation cephalosporins, which are drugs we try to reserve to fight some of the worst infections,” said Dantas. “It was alarming to find genes from the tribespeople that would deactivate these modern, synthetic drugs.”

As for how bacteria could resist drugs that such microbes never before had encountered, the researchers point to the possibility of cross-resistance, when genes that resist natural antibiotics also have the ability to resist related synthetic antibiotics.

“We’ve seen resistance emerge in the clinic to every new class of antibiotics, and this appears to be because resistance mechanisms are a natural feature of most bacteria and are just waiting to be activated or acquired with exposure to antibiotics,” Dantas said.



Funded by the C&D Fund, the Emch Fund, the Helmsley Charitable Trust, SUCCESS, NAKFI Synthetic Biology, a Washington University I-CARES award, the Diane Belfer Program for Human Microbial Ecology, an NDSEG graduate fellowship, a Howard Hughes Medical Institute Early Career Scientist Award, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of General Medical Sciences of the National Institutes of Health (NIH). NIH grants DK062429, DP2-DK098089, R01-GM099538 and UH2AR057506.

Clemente JC, et al. The microbiome of uncontacted Amerindians. Science Advances, published online April 17, 2015. 

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.




Lewis Wall helps tackle problem of Ethiopian girls lacking sanitary pads

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LEWIS WALL
Reusable pads are produced locally by women at the Mariam Seba factory in Mekelle, Ethiopia. The factory was founded by Freweini Mabrahtu, an American-educated Ethiopian who is trying to change the experience of adolescent girls.



In rural Ethiopia, menstruation is a taboo subject, rarely discussed publicly or privately. Many schools don’t have adequate toilets, and girls often can’t afford sanitary pads. They make do with strips of cloth, dry grass and pieces of old mattresses.

Not having adequate bathrooms and sanitary supplies leads to embarrassing situations at school. As a result, girls often stay home three to five days a month and fall behind in their studies. Some eventually drop out.

When Washington University obstetrician-gynecologist L. Lewis Wall, MD, DPhil, and his wife, Helen, lived in Ethiopia last year while he was a Fulbright scholar, the couple met an Ethiopian woman who is trying to change the experience of adolescent girls in rural Ethiopia by providing them with reusable sanitary pads and education about menstruation.

After getting to know the woman, Frewini Mabrahtu, the Walls decided they had to do something to support her mission.

“Menstrual hygiene management is a human right for women,” said Wall, professor of obstetrics and gynecology. “It makes such an impact on girls. How could we not help?”

Wall

So last year, the Walls established a St. Louis-based organization called Dignity Period to raise awareness about the lack of sanitary pads for girls in Ethiopia and to help distribute them to girls in secondary schools.

“Lewis and Helen Wall made me a promise that they would support this project, and that promise became a reality,” Mabrahtu said. “I will be always grateful to the Walls for their involvement. They helped me see the light at the end of the tunnel.”

Making a difference

Mabrahtu earned a bachelor’s degree in chemical engineering in 1992 in Texas and worked for 10 years in the United States. On a visit home to Tigray, a region in northern Ethiopia, she was disheartened to learn that not much had changed for adolescent girls when they begin menstruating. She remembered all too well not having access to sanitary pads, missing school and feeling isolated during her adolescence and young adulthood.

Mabrahtu moved back to Tigray in 2005 determined to make a difference. With a $150,000 loan, she hired 42 local women and started a factory that makes reusable, washable sanitary pads at a cost significantly less than that of commercially available, disposable pads. Today, the factory produces more than 100,000 pads each year.

Mabrahtu’s biggest challenges are lack of financial support and limited ways to distribute pads to girls in secondary schools.

To help with these hurdles, Dignity Period, the organization started by the Walls, is partnering with the factory and the College of Health Sciences at Mekelle University in Tigray, where Wall was a Fulbright Scholar. The aim is to distribute 50,000 kits in 2015 to secondary-school girls in Tigray. Each kit will include four reusable pads, two pairs of underwear, two bars of soap and information about menstruation.

Wall and his colleagues at Mekelle University plan to conduct cultural studies about attitudes toward menstruation in Tigray and develop culturally appropriate educational materials for the local school system.

While at Mekelle, Wall also met with Robin Shepard, DSc, the faculty adviser of the Washington University chapter of Engineers Without Borders USA, who is working with the civil engineering department at Mekelle University to design toilets for schools.

“We, along with other international groups, want to increase the number of toilets in schools,” said Shepard, adjunct instructor in the Washington University School of Engineering & Applied Science. “We want to make sure the toilets that are installed meet the special needs of girls, giving them privacy and a place to wash. The goal of our project is to make sure they attend school every day.”

Wall’s Fulbright scholarship helped establish a residency training program in obstetrics and gynecology at Mekelle University. For the past 20 years, he has worked doggedly to help women in Africa with obstetric fistulas — injuries during childbirth that cause bladder and fecal incontinence.

But he was struck personally by the struggles of girls in rural Ethiopia.

He hopes Dignity Period and other efforts one day will expand to all of Ethiopia and other African countries. “These are problems throughout the world,” he said. “We all need to work to make it easier for adolescent girls to stay in school.”



Finding points to a cause of chronic lung disease

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Holtzman Lab

New research explains how immune cells called macrophages (green) in the lung sometimes stick around too long, even after clearing a viral infection, leading to long-term lung problems. Macrophage nuclei are shown in blue.



Scientists have long suspected that respiratory viruses — the sort that cause common colds or bronchitis — play a critical role in the long-term development of chronic lung diseases such as asthma and chronic obstructive pulmonary disease (COPD).

Studying mouse and cell models of this process, researchers at Washington University School of Medicine in St. Louis now have shown how immune cells dispatched to the lung to destroy a respiratory virus can fail to disperse after their job is finished, setting off a chain of inflammatory events that leads to long-term lung problems.

Understanding such details may help scientists find ways to block the accumulation of inflammatory immune cells and prevent progression to chronic lung disorders.

The study appears April 20 in The Journal of Experimental Medicine.

The findings stem from research into immune cells called macrophages.

“In general, scientists thought this type of macrophage was involved in the repair of the lung,” said senior author Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine at the School of Medicine. “That may be true in some cases. But like many things in nature, too much of a good thing can become a bad thing.”

When large numbers of this type of macrophage accumulate, they appear to stop orchestrating the immune response against acute viral infections and instead participate in a type of response that is more typically directed against parasites and allergens. Holtzman and his colleagues observed that macrophages producing this type of immune response also express a protein called TREM-2 at high levels.

The new work shows that the usual cell-surface form of TREM-2 is indeed needed to sustain the macrophages as they fight off viral infection and the early illness it causes. Then, after the initial infection is cleared, TREM-2 is cleaved from the outer surface of the macrophages. Previously, this cleaved form of the protein was thought to be inactive.

“We were surprised to find that this cleaved form of TREM-2 is actually quite active,” Holtzman said. “It potently prevents the programmed death of macrophages, promoting their survival. So this form of TREM-2 allows for macrophages to hang around longer than they should.”

Holtzman noted that TREM-2 enables a feed-forward process for inflammatory disease. Each new infection activates macrophages, which later produce the cleaved form of TREM-2. This form then promotes further macrophage accumulation and ultimately contributes to ongoing and progressive inflammatory disease.

Implicating TREM-2 in the harmful accumulation of inflammatory immune cells opens the door to exploring ways to block it, according to first author Kangyun Wu, PhD, a staff scientist.

“We don’t yet have a specific drug to interrupt the TREM-2 process,” Holtzman said. “But we now understand the controls for the process, so our drug discovery program is already screening for compounds that might keep TREM-2 at normal levels.”

The researchers also found that the cleaved form of TREM-2 that causes the macrophages to stick around when they shouldn’t does not appear to be involved in the initial immune response to the acute viral infection. So presumably, blocking it should not interfere with the important task of clearing the respiratory virus from the lungs.

Holtzman also pointed out that individual genetic variation in TREM-2 may explain why some people never develop chronic lung disease even after many viral lung infections.

While this study focused on the lung, Holtzman said TREM-2 could be involved in other inflammatory diseases in which the immune system is chronically activated in other organs. He pointed to a possible role in the brain, for example, since related work has associated certain genetic variants of TREM-2 and macrophage dysfunction with Alzheimer’s disease.


The research was supported by the National Institutes of Health (NIH), grant numbers U19 AI07048, T32 HL007317, P50 HL084922, P01 HL029594, R01 HL073159 and R01 HL121791; and by the Martin Schaeffer Fund.

Wu K, Byers DE, Jin X, Agapov E, Alexander-Brett J, Patel AC, Cella M, Gilfilan S, Colonna M, Kober DL, Brett TJ, Holtzman MJ. TREM-2 promotes macrophage survival and lung disease after respiratory viral infection. The Journal of Experimental Medicine. April 20, 2015.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.


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