"algunas cosas no deben de ser olvidadas"/"some things are not to be forgotten" by Patricia De La Parra

Female survivors of violence know anguish, pain and fear.

But that’s not all.

They also know courage, bravery and strength.

The exhibit, “My Name is Strong,” celebrates that power through more than 60 works of art by both survivors of gender-based violence and those who are committed to preventing it.

who co-founded My Name is Strong with two other Brown School graduate students, Jay Celin and Ambar Plasencia, as a commitment to violence prevention.

“A lot of times, people get bogged down by the stories of trauma and these acts of violence. And as awful as those moments are, they don’t have to define us. The trauma is not the be-all and the end-all. That’s why I really wanted to focus on the strength and the bravery, not the trauma and the weakness. I wanted to celebrate those who survive every day and the people who offer support and are fighting back.”

"Against all violence" by Key Sun

My Name is Strong was one of the many student-led projects endorsed by Clinton Global Initiative University, which took place at Washington University in St. Louis in April. Since then, the My Name is Strong has received submissions from as far away as Idaho and New Hampshire; Canada and Libya. The group also hosted open art studios on campus and provided canvases, paint and other art supplies to community partners Safe Connections, YWCA Metro St. Louis Regional Sexual Assault Center and ALIVE Inc. At first, some participants questioned how a paintbrush could help them process their experience.

“People would come in and say, ‘I don’t feel strong.’ And that was OK,” Fish said. “We told people that they didn’t have to create a piece for the exhibit, but what ended up happening in some cases is that they changed their mind. Once they got started, they were able to paint out their feelings.”

“One person said to me, ‘People always want me to explain what it was like or to talk about it or to write about it. If I knew how to do that, I would. That’s why I’m an artist,’” Fish said. “I found that this project really reached those people who were done talking about it or didn't know how to talk about it."

“It makes you realize how prevalent the problem is. That part has been very emotional for me,” Fish said. “But this is also about our community turning this issue on its head and saying, ‘We are strong people and I want to speak up.’ It’s actually a good feeling.”

My Name is Strong

What: A community art exhibit featuring works by family, friends and individuals impacted by gender-based violence.

When: 6-9 p.m. Friday, Sept. 20; WU-Slam poets will perform at 7:30 p.m.

Where: Union Avenue Church, 733 Union Blvd.

More info: My Name is Strong Facebook Page

Anonymous submission from Alive Inc.

Andrew Brimer and Abigail Cohen, May graduates of the School of Engineering & Applied Science at Washington University in St. Louis and co-founders of the med-tech startup Sparo Labs, have won the $150,000 CIMIT Student Technology Prize for Primary Care, bringing their total competition winnings to more than $275,000.

The first undergraduate team to win the prize in the contest’s five-year history, the pair defeated graduate and post-doctoral teams from Massachusetts Institute of Technology, University of California-Berkeley and Johns Hopkins University.

"We are very proud to represent both Washington University and St. Louis in this national competition,” Brimer said. “Abby and I are excited to have our business located in downtown St. Louis at T-REx and be part of the city's thriving startup community. We still have close ties with the university and are very thankful for the support and encouragement we received and continue to receive there as we move forward."

In addition to the seven other competitions that Sparo Labs has won, including an Arch Grant, the Olin Cup and the School of Engineering’s Discovery Competition, the CIMIT funds will enable Sparo Labs to continue building a solution that empowers patients to more effectively manage their asthma.

"It is an amazing accomplishment that Abby and Andrew have managed to fund their seed round entirely through competition winnings,” said Clifford Holekamp, senior lecturer in entrepreneurship at Olin Business School, director of the school’s entrepreneurship platform and co-teacher of the university’s Hatchery business incubator course, which helped the pair hone their idea.

"Abby and Andrew represent the very best of our student entrepreneurs,” he said. “Working as a team, they have combined creativity with discipline and determination. The results are showing us all what is possible."

Sparo Labs is developing an award-winning, patent-pending spirometer system that can be produced for a fraction of the cost of current spirometers today, while seamlessly connecting with smartphones via mobile and web apps.

Cohen and Brimer hope that putting this powerful device in the hands of patients will revolutionize how respiratory diseases are managed — empowering patients to quantitatively track and proactively control their asthma and equipping doctors with the power of objective and real-time data to better and more efficiently manage their patients.

“Abby and Andrew are truly exceptional people who developed a remarkable initial idea into full-fledged products, careers and a company,” said Kurt Thoroughman, PhD, associate professor of engineering and director of undergraduate studies at the School of Engineering & Applied Science.

“One very unique feature of Washington University is accessibility: we have world-class schools, centers, departments and faculty, all of which are committed to working across our academic community,” Thoroughman said. “Abby and Andrew were able to pioneer, nurture and develop their ideas independently, seeking just the proper help at the proper time from resources in School of Engineering and across the university. Abby and Andrew complemented their independence and insight with willingness, openness and trust to seek and get what they needed to flourish, and we are thrilled that Washington University could provide the broad and deep environment for them to launch Sparo Labs.”

Brimer and Cohen said they owe much of their success to the nurturing entrepreneurial spirit of the university.

“The university is doing a great job promoting and encouraging entrepreneurship on all levels, from the ‘back of a napkin ideas’ that can be pitched at an IdeaBounce, to the Olin Cup or Discovery Competition that help foster more developed or mature projects into real companies with serious funding,” Brimer said. 

“Washington University’s focus on entrepreneurship has allowed us and other students the ability to get valuable feedback and funding to help turn ideas into viable companies with large potential for impact,” Cohen said.

The pair has received mentorship from the Skandalaris Center for Entrepreneurial Studies, the Hatchery entrepreneurship course at Olin Business School taught by Holekamp and from Mario Castro, MD, director of the Asthma and Airway Translational Research Unit at the School of Medicine.

About CIMIT

CIMIT is the Center for Integration of Medicine and Innovative Technology. A 15-year-old nonprofit consortium of Boston-area teaching hospitals and engineering schools, CIMIT brings innovators together to explore, develop and implement novel technological solutions for today’s most urgent health-care problems. Participants in the consortium are Beth Israel Deaconess Medical Center, Boston Medical Center, Boston University, Brigham and Women’s Hospital, the Charles Stark Draper Laboratory, Children’s Hospital Boston, Harvard Medical School, Massachusetts General Hospital, Massachusetts Institute of Technology, Newton-Wellesley Hospital, Northeastern University, Partners HealthCare and VA Boston Healthcare System.

Samer S. Shehata, PhD, a leading expert on Middle East politics, will give the keynote talk at “The Crisis in Egypt” public symposium at 4 p.m. Monday, Sept. 23, in Umrath Lounge.

The symposium, which will be held in Umrath Lounge, also will feature a roundtable discussion and presentations on the latest developments in Egypt. 

Shehata, an associate professor of Middle East studies in the Department of International and Area Studies at the University of Oklahoma, is a specialist on Egyptian politics and the Muslim Brotherhood.

The title of his address is “Egypt: From Uprising to ‘Coup’ to Democracy?”

Shehata, an Egyptian native, also will participate in the roundtable discussion during the two-hour symposium, which is sponsored by the Department of Jewish, Islamic and Near Eastern Languages and Cultures (JINELC) and the College of Arts & Sciences.

“Events in Egypt have moved very fast and often in confusing directions over the past several months. A lot is at stake in Egypt and in other countries, including the U.S., in understanding the complexity of these events and the outcomes of current struggles,” said Nancy Y. Reynolds, PhD, an associate professor of JINELC and of history, both in Arts & Sciences.

“We are fortunate to be able to benefit from Dr. Shehata’s tremendous expertise in Egyptian politics, with particular emphasis on the Muslim Brothers, Egyptian elections and Egyptian workers,” said Reynolds, who specializes in the social, cultural and economic history of 20th-century Egypt.

Reynolds, who organized the symposium, will discuss “Women and the Gender Politics of Egypt’s Islamist Movement.”

She is author of A City Consumed: Urban Commerce, the Cairo Fire, and the Politics of Decolonization in Egypt (Stanford University Press, 2012).

The other presenters are:

• Arts & Sciences senior Mahroh Jahangiri, an international and area studies and political science major, who will give “An Egypt Primer for Those Too Embarrassed to Ask.”

Jahangiri received a Social Change Grant from WUSTL’s Gephardt Institute for Public Service in 2012 and spent that summer in Cairo establishing a program at the Children’s Cancer Hospital Egypt to help child cancer patients continue their education while hospitalized. 

Jahangiri also conducted research on gender violence in Tahrir Square.

• Anne-Marie McManus, PhD, an assistant professor of modern Arabic literature and culture in JINELC, who will discuss “Writers, Intellectuals and the Struggle for Change.” 

McManus, who recently earned a doctorate in comparative literature from Yale University, teaches on 19th- and 20th-century literatures, literary and gender theory, and the history of political thought. One of her areas of research is contemporary Syrian literature and film.

Shehata previously taught at the American University in Cairo, Columbia University, New York University, and Georgetown University. He is the author of Shop Floor Culture and Politics in Egypt (SUNY, 2009 and republished with a new “Afterward” by the American University in Cairo Press in 2010), and editor of Islamist Politics in the Middle East: Movements and Change (Routledge, 2012). 

He is finishing a new book on the Egyptian Muslim Brotherhood’s shift from an opposition movement to the dominant political party between 2005 and 2011.

His analysis and op-ed pieces have been published in The New York Times, Boston Globe/International Herald Tribune, Salon, Slate, Arab Reform Bulletin, Al Hayat, Al Ahram Weekly and other publications.

Shehata has provided commentary for a wide range of media, including CNN, BBC, PBS News Hour, NPR, Al Jazeera, Middle East Broadcasting Company, The New York Times, Washington Post, Financial Times, Guardian, Le Monde and the Sydney Morning Herald.

For more information on the symposium, contact the Department of Jewish, Islamic and Near Eastern Languages and Cultures at jinelc@wustl.edu.

More than a century ago, Alois Alzheimer, a Bavarian physician, first identified the neurodegenerative brain condition that came to be known as Alzheimer’s disease. Finding ways to diagnose and treat this disease has frustrated scientists and clinicians ever since.

 Jerry Naunheim

Scientists Randall Bateman and John Morris explain the goals of Alzheimer's research at the Charles F. and Joanne Knight Alzheimer’s Disease Research Center. Bateman is principal investigator for a first-of-its-kind trial to evaluate whether drug treatments can prevent Alzheimer's before dementia begins.

Now the long and hard-fought campaign against Alzheimer’s has reached a potentially significant milestone: the launch of the first clinical trials to test whether giving new drug treatments before dementia can prevent Alzheimer’s.

Brent Whitney, 34, who has an inherited form of Alzheimer’s but does not yet have symptoms of the disease, hopes to participate in the study. The lives of his grandmother and 10 of her 13 siblings were cut short by the Alzheimer’s gene mutation, and the mutation continues to affect succeeding generations of the family.

“The start of this trial is a very exciting moment in Alzheimer’s disease research, and it gives me renewed hope for a future without Alzheimer’s,” Whitney said. “I hope my grandchildren someday learn of this condition in history books, like I learned about polio.”

The trial is testing two new drug treatments and is led by principal investigator Randall Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor in Neurology at Washington University School of Medicine in St. Louis and director of the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU).

“We believe that the diverse portfolio of drugs and approaches of the DIAN-TU trial will accelerate the discovery of an effective treatment for Alzheimer’s,” Bateman said. “This trial is possible because of the outstanding support of multiple stakeholders, including patients and family members, pharma partners, the Alzheimer’s Association, the National Institutes of Health, academic researchers and highly dedicated trial operations groups.”

The new trial is funded by a unique mix of private and public resources, including:

• A grant from the National Institutes of Health (NIH) for fiscal 2013 in the amount of $1.5 million, awarded Sept. 18, with the total amount of as much as $6 million over the four years of the project;

• The largest Alzheimer’s Association grant given to date, nearly $4.2 million;

• Donation of the treatments used in the trials from the drugs’ manufacturers, Roche and Eli Lilly & Co., which also provided major financial support for the trial;

• Donation of a new agent for imaging brain plaques, Amyvid, by Avid Radiopharmaceuticals Inc., a wholly owned subsidiary of Lilly; and

• Donation by CogState of a computerized set of cognitive skills tests to help assess cognitive function in participants.

John C. Morris, MD, is director of the Charles F. and Joanne Knight Alzheimer’s Disease Research Center and principal investigator of the Dominantly Inherited Alzheimer Network, which laid much of the scientific groundwork that made a DIAN-TU trial of preventive treatments possible.

“Trying to prevent Alzheimer’s symptoms from occurring is a new strategy, but much of what we’ve learned in recent years about Alzheimer’s and the brain has suggested that prevention has a significantly better chance of succeeding than treatment after cognitive impairment,” said Morris, the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology. “We are most appreciative of the support we have received to test this new approach.”

For more information on the trial, see www.DIANXR.org.

One of the treatments under study in the new trial is gantenerumab, an antibody made by Roche that binds to all forms of aggregated amyloid beta and helps remove them from the brain.

Another treatment that will be evaluated is a monoclonal antibody known as solanezumab that binds to soluble monomeric forms of amyloid-beta after they are produced, allowing them to be cleared before they clump together to form beta-amyloid plaques.

David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of neurology, is listed on the patent related to the antibody that is co-owned by Washington University in St. Louis and Lilly. Washington University has licensed its patent rights to Lilly. The financial interests of the university and Holtzman in this patent are managed in accordance with applicable conflict-of-interest policies and regulations.

Won Ju Lim, 24 Seconds of Silence, 2008. Mixed media sculptures and 5 video projections. Dimensions variable. Exhibition view, Ullens Center for Contemporary Art, Beijing, China. Courtesy of Guy & Myriam Ullens Foundation, Geneva, Switzerland. Photo: Sun Jianwei.

In her video installation A Brief History of Collapses, Brooklyn-based artist Mariam Ghani explores the histories, myths and uncanny architectural similarities between the Museum Fridericianum in Kassel, Germany, and the Dar ul-Aman Palace in Kabul, Afghanistan. Today, the former has been rebuilt as the primary venue for the art fair dOCUMENTA. The latter remains a ruin.

Architecture, memory and travel also inform the work of the Korean-born, Los Angeles-based artist Won Ju Lim. In Baroque Pet Shop (2010), Lim layers video of Baroque cathedrals with miniature cities sculpted from ephemeral materials and abstracted images that variously recall fish bowls, caged birds and scratching posts.

Now, the Saint Louis Art Museum and the Sam Fox School of Design & Visual Arts at Washington University in St. Louis are pleased to announce that both artists have been selected as Henry L. and Natalie E. Freund Teaching Fellows.

Lim will serve as the Freund Fellow for the 2013-14 academic year. Ghani will serve as Freund Fellow for 2014-15.

Supported by the Henry L. and Natalie E. Freund Endowment Fund, Freund Fellowships promote the exhibition and acquisition of contemporary art at the Saint Louis Art Museum, as well as the teaching of contemporary art principles in the Sam Fox School. Each fellowship consists of two month-long residencies, during which recipients teach in the Sam Fox School and prepare an exhibition for the museum’s Currents series.

* The Berlin-based team of Renata Stih and Frieder Schnock, the 2012-13 Freund Fellows, will discuss their work at 6 p.m. Tuesday, Sept. 24, at the Saint Louis Art Museum. Their exhibition, Currents 107: Renata Stih & Frieder Schnock, will open at the museum Friday, Sept. 27.

Mariam Ghani, A Brief History of Collapses (2011-12). 2-channel HD video, 7.1 channel audio installation, with custom screens and benches, dimensions variable. Installation view at dOCUMENTA (13). Commissioned by dOCUMENTA (13), with additional support from the Graham Foundation. Photo by Roman Maerz. Courtesy of the artist.

Constructing and deconstructing identity

The selection committee was led by Patricia Olynyk, director of the Graduate School of Art, and Tricia Y. Paik, associate curator of modern and contemporary art for the Saint Louis Art Museum.

“Lim’s rich multimedia practice is exemplary of the way many artists are choosing to work today, no longer tied to a singular medium or approach,” said Paik."Lim brings together video projections, sculpture, models, drawings, photography and collages to create enthralling integrated environments.”

“Among the art shown at dOCUMENTA last year, I thought Ghani’s A Brief History of Collapses was a standout,” Paik said. “Drawing from extensive research of her topic at hand, Ghani produces incisive video installations, photography and performances that investigate, as the artist says, ‘the messy trailing bits around the edges of history.’”

Olynyk, the Florence and Frank Bush Professor of Art, also was struck by the dOCUMENTA installation.

“Mariam’s work probes the complex ways in which various communities construct and deconstruct their identities, particularly in border zones and transnational territories where conflict is prevalent and unavoidable,” Olynyk said. “Her research of cultural history, collaborative methodologies, and use of archives will provide a unique working model for our students.

“I am particularly excited about the arrival of Won Ju Lim this fall,” Olynyk added. “Won Ju’s evocative illuminated installations, which offer a stunning cinematic staging of the metropolis and other urban environments, will no doubt resonate with our MFA students — and, I suspect, equally with our graduate architecture students.”

Won Ju Lim, Baroque Pet Shop, 2010. Mixed media sculptures and five video projections. Dimensions variable. Created with support from Tribeca Film Institute Media Arts Fellowship funded by the Rockefeller Foundation, New York, NY. Photo by Fredrik Nilsen.

Won Ju Lim

Her numerous honors and awards include the Tribeca Film Institute Media Arts Fellowship, funded by the Rockefeller Foundation; the Korea Arts Foundation for Visual Arts Grant; and a California Community Foundation Emerging Artist Fellowship.

Lim’s work is included in the permanent collections of the Hammer Museum and the Museum of Contemporary Art, Los Angeles; Vancouver Art Gallery; Guy and Myriam Ullens Foundation, Geneva; KKR Ltd, Sao Paulo; Constellation Partners, Las Vegas; and La Coleccion Jumex, Estado de Mexico.

Mariam Ghani, The Trespassers (2010-11). Installation with 1-channel HD video, 4-channel sound, and archive, dimensions variable. Installation view at the Sharjah Biennial 10, photo by Alfredo Rubio. Commissioned by the Sharjah Art Foundation. Courtesy of the artist.

Ghani teaches video, new media, public practices and research-based practices at the Pratt Institute in New York. She also serves as an artist-in-residence at New York University’s Asian/Pacific/American Institute.

Her work has been featured at major museums and festivals around the world, including the International Film Festival Rotterdam (2013), dOCUMENTA 13 (2012), the Museum of Modern Art, New York (2011), the Sharjah Biennials 10 and 9 (2011, 2009), the National Gallery in Washington, D.C. (2008), the Tate Modern, London (2007), d/Art, Sydney (2006), EMAP, Seoul (2005), the Liverpool Biennial (2004) and transmediale, Berlin (2003). 

Ghani has collaborated with artist Chitra Ganesh since 2004, as the experimental archive Index of the Disappeared; with choreographer Erin Ellen Kelly since 2006 on the video series Performed Places; and with media archive collective pad.ma since 2012 on the digitization and dissemination of the Afghan Films archive.

The Saint Louis Art Museum is one of the nation’s leading comprehensive art museums with collections that include works of art of exceptional quality from virtually every culture and time period. Areas of notable depth include Oceanic art, pre-Columbian art, ancient Chinese bronzes and European and American art of the late 19th and 20th centuries, with particular strength in 20th-century German art. Admission to the Saint Louis Art Museum is free to all every day.

Sam Fox School of Design & Visual Arts

The Sam Fox School supports the creation, study and exhibition of multidisciplinary and collaborative work. Offering rigorous art and architecture education at both the undergraduate and graduate levels, the Sam Fox School links four academic units — the College of Art, College of Architecture, Graduate School of Art and Graduate School of Architecture & Urban Design — with the university's nationally recognized Mildred Lane Kemper Art Museum.

The Program in Audiology and Communication Sciences (PACS) at Washington University School of Medicine in St. Louis has received a five-year, $1.18 million grant from the U.S. Department of Education to prepare graduate-level teachers of deaf or hard-of-hearing children.

The grant, awarded through the Office of Special Education Programs, will provide significant tuition support to students in the master of science in deaf education (MSDE) program in PACS. The grant will fund scholarships for 40 future teachers in the two-year program, beginning in 2014. Heather Hayes, PhD, assistant professor and director of Deaf Education Studies, is the project director on the grant.

Developments in newborn hearing screening programs and hearing devices have had considerable effects on speech, language and educational success of children who are deaf or hard of hearing. A combination of early diagnosis and advanced hearing devices, such as cochlear implants, has changed the landscape of educational opportunities for this population of children. However, being identified early and receiving a cochlear implant or hearing aid does not assure that a child will develop successful speech, language and literacy skills.

As a result, demand is growing for teachers with expertise in teaching listening and spoken language, as well as knowledge of the latest in audiology and speech and hearing science. The unique environment of PACS provides future teachers with the evidence-based skills they need to best serve children who are deaf or hard of hearing. 

Holden Thorp, PhD, provost and executive vice chancellor for academic affairs at Washington University in St. Louis, has appointed an eight-member committee to identify candidates for the position of dean of the School of Law.

Kent D. Syverud, JD, dean and the Ethan A.H. Shepley Distinguished University Professor, recently was named Syracuse University’s next chancellor. He will begin transitioning to that role Nov. 24.

“We are happy for Kent and proud that he has been selected to lead Syracuse University to greater heights,” Thorp said.

Keating

Daniel Keating, JD, the Tyrrell Williams Professor of Law, will serve as interim dean. At the law school, Keating has served twice as interim dean, as well as vice dean and associate dean.

"Dan Keating has stepped up time and time again to serve his school,” Thorp said. “He enjoys the respect of his colleagues and the confidence of the administration in steering the law school through this interim period."

Thorp and the search committee will work to have a new law dean in place by July 1.

“This is an important search at a challenging but exciting time in legal education,” Thorp said. “The Washington University School of Law has grown and improved considerably in recent years and is poised for another exciting chapter.”

The committee

Edward F. Lawlor, PhD, dean of the Brown School and the William E. Gordon Distinguished Professor, will chair the law dean search committee.

Lawlor

"We are grateful to Eddie Lawlor and the distinguished committee for committing their time and judgment to this most important search,” Thorp said.

“Eddie's vast experience as a dean makes him uniquely qualified to help us find the best leader for our magnificent law school."

In addition to Lawlor, committee members are:

• Howard Cayne, JD, partner at Arnold & Porter, law school alumnus and member of the university’s Board of Trustees;
• Cort VanOstran, third-year law student;
• Peggie Smith, JD, the Charles F. Nagel Professor of Employment and Labor Law;
• Hillary Sale, JD, the Walter D. Coles Professor of Law;
• Pauline Kim, JD, the Charles Nagel Professor of Law;
• John Drobak, JD, the George Alexander Madill Professor of Real Property & Equity Jurisprudence; and
• Matthew Gabel, PhD, professor of political science in Arts & Sciences.

Robert Boston

Daniel Coyne, MD, talks with Corliss Donloe, of St. Louis, as she receives kidney dialysis. Coyne is a highly regarded nephrologist who spent years fighting against the overuse of Epogen, an anti-anemia drug, in patients on dialysis.

The procedure can be exhausting, especially for those who are older – the average age of Coyne’s patients is 65. Many of them also suffer from chronic conditions like diabetes and hypertension and face great difficulties navigating the health-care system.

But Coyne considers caring for his patients a privilege. “We practice in an urban area, surrounded by people frequently neglected by our health-care system,” Coyne explained. “That’s one of the things that appealed to me about going into nephrology. In some ways, this can be a forgotten population, and it’s extremely gratifying to provide their care.”

Coyne directs dialysis at Washington University’s Chromalloy American Kidney Center on the Medical Campus and plays a role at two university-affiliated outpatient dialysis clinics. About 500 patients receive dialysis each week at the three locations.

But Coyne’s concern for dialysis patients extends far beyond the university’s clinics. He’s a strong believer in putting patients’ interests first, and that philosophy inspired him to lead the charge against widespread overuse of the anti-anemia drug Epogen in dialysis patients.

Coyne’s own investigation into the practice consumed more than eight years of his career and exposed the way close ties between pharmaceutical companies and physicians can put patients’ lives at risk.

“Dan took an early and principled stand against what proved to be the overuse of synthetic erythropoetin to treat the anemia of end-stage renal disease,” said Marc R. Hammerman, MD, the Chromalloy Professor of Renal Diseases and chief of the renal division in the Department of Medicine. “Others may have questioned the wisdom of using large doses of the drug but chose to remain on the sidelines. In contrast, Dan had both the scientific credentials and courage of his convictions to ensure that the right thing was done for patients.”

Most patients on dialysis develop chronic anemia because they can’t produce enough red blood cells, which carry oxygen from the lungs to the rest of the body. A severe shortage of red blood cells can be life-threatening, and for years the standard treatment was blood transfusions, but they, too, carry risks.

Then, in 1989, the U.S. Food and Drug Administration approved the drug Epogen to boost red blood cell production and prevent the need for blood transfusions in dialysis patients. Epogen went on to become one of the most lucrative drugs sold in the United States, yielding $2.5 billion annually in profits from its use in dialysis patients alone. But Coyne’s painstaking research has shown that the benefits of the drug were overblown and that potentially deadly side effects, including heart attacks and strokes, were missed.

“By 2004, I had become convinced that doctors were unnecessarily overtreating anemia and using far too much of the drug,” Coyne explained. “My research focused on highlighting the lack of data to support aggressive anemia treatment and the dangers of Epo.”

Coyne does not dispute that Epogen is a life-saving drug for patients with severe anemia. His concerns centered on high doses of the drug that were routinely given to treat mild or moderate anemia. Even today, most dialysis patients get some Epogen, “but you don’t need to give very much of the drug to prevent the need for transfusions,” he said.

As part of his research, Coyne uncovered misleading data on Epogen in a major study published in 1998 in The New England Journal of Medicine (NEJM). The study’s results raised concerns about the safety of the drug – showing a trend toward more deaths – but the statistical analysis in the journal did not tell the full story. Rather, the data led physicians to assume that the results did not reach statistical significance and that higher doses of the drug helped patients feel better.

In fact, while Epogen raised red blood cell counts and prevented the need for transfusions, it also increased the risk of heart attacks, blood clots and death. The drug also did not extend patients’ lives by keeping anemia in check, as had been hoped. But without a thorough statistical analysis, the dangerous side effects were missed because dialysis patients often die from heart problems, Coyne said.

After the study’s publication, use of the drug skyrocketed in patients with milder anemia, encouraged by marketing from Amgen, the drug’s maker. By 2005, Epogen was costing Medicare $2 billion a year, more than any other drug.

Physicians and dialysis clinics had financial incentives to prescribe high doses of Epogen, Coyne said, because they could mark up the cost of the drug, which was administered at the time of dialysis. The more they prescribed to patients, the more profits they made.

In his own practice at the School of Medicine, Coyne did not see benefits of prescribing high doses of Epogen. And information from the U.S. Department of Health and Human Services, which collects data on dialysis patients throughout the country, did not indicate a survival advantage.

“We looked at the survival data from year to year,” Coyne explained. “And the patients on dialysis, despite billions of dollars being spent on the drug, weren’t living any longer. So clearly, aggressive treatment for anemia was not benefiting most patients.”

Frustrated, Coyne filed a Freedom of Information Act request with the FDA in 2008 asking for the complete results of the earlier trial in NEJM. It took 3 ½ years before he received a response.

With the data eventually in hand, Coyne found significant discrepancies between the actual data and the published results in NEJM. He showed that the unadjusted results were statistically significant – there were more heart attacks and deaths among patients receiving the higher doses of Epogen – but that information had not been published. The full data also showed that higher doses of Epogen did not improve patients’ quality of life.

Two weeks before Coyne received the trial data, the FDA added new warnings to the package inserts for Epogen. Today, Coyne feels vindicated.

“The new labeling states that there are no risk-free doses of the drug, and maintaining patients at moderate anemia is better and certainly safer than giving them heavy doses of drugs that carry a lot of dangers like heart attacks and strokes,” he said.

Despite Epogen’s labeling change, Coyne has continued to analyze data on the drug and publish results. Writing in The Scientist in May 2012, Coyne noted, “Finally, as strange as it seems, I am now the sole author of the publication on the predefined primary and secondary results of the largest outcomes trial of [Epogen] in dialysis patients, and I didn’t even participate in the trial.”

Throughout the close look into Epogen, Coyne said he had the full backing of the university.

“The great strength of Washington University is that the administration allowed me to pursue this financially disadvantageous but patient-centered research, which exposed how pharma and dialysis companies were putting their own interests ahead of our patients,” he added.

Even as Coyne pursued his research into the risks of Epogen, he continued to provide exceptional care to his patients on dialysis. Today, much of their management is multidisciplinary, involving a team of doctors, a nurse practitioner, dietitians and social workers.

“We see all patients during their dialysis treatment at least once a week and deal with any acute issues they may have had,” he added. “Working together, my colleagues play a huge role in keeping patients happy and healthy.”

And Coyne continues to provide care that serves his patients’ best interests. “The story of pharmaceutical companies spinning research to sell drugs has occurred over and over again,” he said. “I do think there’s progress in making clinical trial data available to the public and to physician scientists, but we have a long way to go, and it’s still not clear to me that patient safety will be at the apex of the system.”

Daniel Coyne, MD, pictured with his children while on vacation in Maui, Hawaii. All have followed in his footsteps, pursuing degrees in the sciences. From left, Kathleen, graduated from Murray State with a health sciences degree; Bridget studies nursing at Bellarmine University; Kevin studies chemical engineering at the University of Dayton; and Sarah is a medical student at the University of Cincinnati.

​

Edgar Degas, Sur la scène (On Stage III), 1877. Etching, 3 3/4 x 4 7/8". Mildred Lane Kemper Art Museum, Washington University in St. Louis. University purchase, Yalem Fund, 2005.

This fall, four Washington University in St. Louis cultural areas have banded together to create Arts First, a multidisciplinary, campuswide subscription package.

It works like this: For $40, students, faculty and staff may purchase an Arts First card, which provides admittance to four campus events over the next year.

Che Malambo brings Argentine dance to Edison Nov. 22.

These include a special, members-only tour at the Mildred Kemper Art Museum Oct. 11, as well as one event of their choice from Edison Theatre, one event from the Department of Music in Arts & Sciences and one event from the Performing Arts Department, also in Arts & Sciences.

Arts First cards can be purchased at the Edison Theatre Box Office or through the First Year Center website. For more information or a list of eligible events, visit the Arts First website or call (314) 935-6543.

Actor and playwright Stephen Lang — perhaps best known for his role as Col. Quaritch in Avatar— brings Beyond Glory, an unflinching portrait of the real lives behind stories of military heroism, to Edison Nov. 16.

Nick Miller recently returned from Georgetown University Hospital in Washington D.C., where he donated stem cells to a leukemia patient through Be The Match.

Yes, English graduate student Nick Miller joined the bone marrow registry to honor his grandfather, who died of leukemia when Miller was a boy. 

“There is a family connection to a lot of the different blood cancers and maybe subconsciously that motivated me,” said Miller, who registered at a campus drive four years ago. “But at the time I thought, ‘So I can stop for a second, get my cheek swabbed and potentially save someone’s life? Why wouldn’t I do that?’”

Miller learned this year he was, indeed, a match. He returned just two weeks ago from Georgetown University Hospital, where he donated stem cells and plasma. All he knows about the recipient is that she’s a woman, 42, lives abroad and suffers from leukemia. He hopes she’s responding to treatment, though in a way, it doesn’t matter. 

After registering, Miller received emails from time to time confirming his contact information. But not until this spring did the registry find a potentional match. Miller took additional blood tests and then, five days before his scheduled procedure, received daily injections to stimulate his stem cell production. On Sept. 2, Be The Match flew Miller to Washington, D.C., for the procedure. The organization also paid for his lodging, transportation and meals.

The procedure itself took several hours but was relatively painless. In the past, bone marrow donors underwent surgery. Today most donors, like Miller, have their blood drawn by a machine which siphons off the stem cells and plasma. 

“It’s nowhere near as invasive,” Miller said. “There was one other donor at the same time and we kept on jokingly saying it was going to be a race to see who was going to finish first.”

The next day, Miller’s stem cells flew one way and Miller flew the other. He was back in St. Louis in time to teach his Rodriguez Scholars freshmen seminar, "Latino/a Experiences in the United States." The entire trip took about 48 hours.

“In a way it seems silly that I didn’t do this earlier,” Miller said. “It was a pretty minimal sacrifice from me to potentially save someone’s life.” 

When: 10 a.m.-2 p.m. Thursday, Sept. 26, at Lopata Hall Gallery and 5-7:30 p.m. at Ursa’s Stageside
More information: wumr.wustl.edu

In the wild, animals use color and pattern to disguise themselves from predators. But last spring, a team from Washington University in St. Louis flipped the calculus. How, they asked, do we keep human observers from disturbing animals in their natural environments?

Over the last nine months, that question has been one of the driving forces behind the creation of a new avian observatory located near the confluence of the Mississippi and Missouri Rivers. The area represents an important habitat for trumpeter swans, great blue herons, bald eagles, gulls, geese, pelicans and other wildlife that, each spring and fall, migrate along the Mississippi flyway.

Working in collaboration with the Audubon Center at Riverlands and the U.S. Army Corps of Engineers’ Rivers Project Office, more than two dozen architecture students from the university’s Sam Fox School of Design & Visual Arts deployed cutting-edge digital fabrication technology to design and build the observatory. It was formally dedicated Aug. 28.

Leading the project were Andrew Colopy and Ken Tracy, both visiting assistant professors in the Sam Fox School.

The project team included: Nike Cao, Emily Chen, Wassef Dabboussi, Duan Duan, Can Fu, Jina Kim, Masha Konopleva, Chun Liu, Joe Lomas, Yiyang Min, David Orndorff, Yiming Pan, Glenn Park, Chris Quinlin, Yu Rong, James Struthers, Yilong Wang, Nash Waters, Hao Wu, Yao Xia, Yu Xin, Shuojin Yang, Haosheng Zhang and Han Zhu.

Creation of the observatory was funded by the Sam Fox School, the Audubon Center and the Army Corp of Engineers, with additional support from WUSTL's Gephardt Institute for Public Service.

From left to right: Emily Chen, James Struthers, Andrew Colopy and Joe Lomas finishing work on the recently completed avian observatory at the Audubon Center at Riverlands. Photo by Danny Reise/WUSTL Photos.

Chinese search engine conglomerate Baidu Inc. leads the pack in a new ranking of the 50 most innovative companies in the world.

Knott

RQ, which was featured in the May 2012 Harvard Business Review article, “The Trillion Dollar R&D Fix," is a measure of research-and-development (R&D) productivity linking R&D spending to firm growth and market value.

“RQ is the missing link explaining Goldman Sachs’ correlation between R&D spending and stock returns in their report 'The Search for Creative Destruction.' It’s not that spending more on R&D generates higher returns, it's that firms with high RQ have higher optimal R&D, as well as higher returns per R&D dollar," Knott said.

One concern with the report, Knott said, is that readers may walk away with the impression that increasing R&D increases returns. 

"This simply isn’t true," she said. "For many of the pharmaceutical firms, R&D is above optimum levels. In those cases, profits and market value would be higher if they cut R&D. RQ tells you when that’s likely.”

“Firms are beginning to use RQ to gauge their R&D capability, and to establish their R&D budgets, which I’m really excited about," Knott said. "This should restore R&D’s role as the engine of economic growth. One thing impeding that has been that R&D spending is an easy target under investor pressure for quarterly earnings. Cutting R&D increases profits immediately, but its benefits are uncertain as well in the future, so they get too heavily discounted."

Knott is excited by the fact that historically, RQ50 portfolios substantially outperform the indexes. 

"This should get investor attention," she said. "This opportunity for abnormal returns arises because firms in the RQ50 often fly below investor radar. If you look at the list, you’ll notice these aren’t the firms that typically come to mind when folks draw up innovator lists. The only RQ50 firm to consistently appear in other rankings is Amazon, which ranks sixth.”

For a full list of the RQ50, visit amkanalytics.com/Pages/rq50.

An international team of researchers has identified a genetic mutation linked to age-related macular degeneration (AMD). Shown is an eye with signs of macular degeneration.

An international team of researchers, led by scientists at The Genome Institute at Washington University School of Medicine in St. Louis and the University of Michigan School of Public Health in Ann Arbor, has identified a gene mutation linked to age-related macular degeneration (AMD), the leading cause of blindness in Americans over age 50.

It’s not the first gene variation linked to AMD, but it is the first to suggest a mechanism where the variant may contribute to the disease. The researchers report that a change in the C3 gene, which plays a role in inflammation and in the body’s immune response, also contributes to macular degeneration.

The study was published online Sept. 15 in the journal Nature Genetics.

“In past studies of AMD, there is a clear relationship between the complement pathway and the onset of this disease,” said co-senior investigator Elaine R. Mardis, PhD. “The complement system is part of the immune system that helps amplify or ‘complement’ the efforts of immune cells to fight infections. So the idea is that the gene variant interferes with the complement pathway’s normal function throughout life, and that can damage the retina over time, which ultimately leads to AMD’s emergence.”

The researchers sequenced DNA from 10 regions of the genome that had been linked to AMD in previous genetic studies. They analyzed a total of 57 genes in 2,335 patients with macular degeneration. Then the researchers sequenced the same genes in 789 people of the same age who did not have AMD.

The search turned up two gene variants: one in the C3 complement gene, and an alteration that had been identified in previous studies of macular degeneration.

“Finding the variant that had been identified previously helped confirm that we were on the right track,” explained Mardis, a professor of genetics and co-director of the Genome Institute. “And it’s likely this new variant was discovered because of the very large number of patients whose DNA we sequenced. By analyzing so many AMD patients, it was possible to find variants that may not have been identified in a smaller patient sample and to establish that this C3 gene variant is unique to people with AMD.”

The two gene variants together contribute to a three-fold increased risk for macular degeneration. Mardis and her co-investigators hypothesize that the mutations work in tandem to increase AMD risk by interfering with the inactivation of complement in the retina.

Mardis

The next step, according to Mardis, is to look at additional DNA regions in the more than 2,000 patients and controls who were involved in this study. The researchers will broaden their look across the genome and go beyond the 10 regions of DNA that were analyzed in this study.

“We hope to identify new genes — perhaps more genes in the complement pathway, perhaps genes in other inflammatory response pathways, or in areas we wouldn’t have anticipated finding any genes related to AMD,” she said. “We’re taking a wide look at the genome to see what turns up.”

Funding for this research comes from the National Eye Institute (NEI), and the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH). Other funding comes from the Medical Research Council, UK; the Deutsche Forschungsgemeinschaft; the Alcon Research Institute; the UK Department of Health’s National Institute for Health Research (NIHR) Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and the UCL Institute of Ophthalmology: Research to Prevent Blindness; the Thome Memorial Foundation; the Harold and Pauline Price Foundation; and the National Health and Medical Research Council of Australia (NHMRC) Clinical Research Excellence. The study also was supported by the Intramural Research Program (Computational Medicine Initiative) of the NEI.

NIH grant numbers EY022005, HG007022, HG005552, EY016862, U54HG003079 and EY09859.

Zhan X, Larson DE, et al. Identification of a rare coding variant in complement 3 associated with age-related macular degeneration. Nature Genetics, Advance Online Publication, Sept. 15, 2013.
doi:10.1038/ng.2758

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.

The human body has a lot of jobs to do, and its mechanical features, such as strength and flexibility, are important to how well it does them. Washington University in St. Louis engineers are now applying a new imaging technique to a model of brain tissue to see how stiff or soft it might be.

Philip Bayly, PhD, the Lilyan and E. Lisle Hughes Professor of Mechanical Engineering and chair the Department of Mechanical Engineering & Materials Science, has received a three-year, $429,222 grant from the National Science Foundation to study directionally dependent mechanical properties in muscle, white matter in the brain or artificial tissue.

In the brain, white matter holds the nerve fibers that wire cells together. Fibers in tissue also determine mechanical stiffness and strength and influence in which direction waves travel during motion. But these fibers also make it difficult to measure the properties without taking invasive measures.

Bayly and Joel Garbow, PhD, research associate professor of radiology at the School of Medicine, plan to use magnetic resonance elastrography (MRE), a noninvasive technique, to view and measure different properties of waves when they travel in different directions in the fibrous materials. There are a variety of factors that come into play.

“The speed of the waves depends on the stiffness of the material,” he said. “The more stiff the material, the faster the waves travel. In fibrous materials, such as muscle and white matter in the brain, stiffness depends on direction. So we plan to use waves propagating in different directions with different polarizations to study the mechanical properties of these tissues.”

What they determine ultimately could lead to new diagnostic tools for nerve and brain disorders and new insight into how artificial tissue degrades over time.

This research is related to Bayly’s National Institutes of Health-funded work into understanding brain biomechanics in traumatic brain injury. 

As part of the project, Ruth Okamoto, DSc, senior research associate in Mechanical Engineering & Materials Science, will use a common “biomaterial” to mimic the brain inside the skull – Jell-O gelatin in a clear glass bowl. 

Participants in Youth University, a Campus Y program encouraging local middle school students to begin thinking about college, will visit the lab for demonstrations of how forces on the skull create motion in the brain.

“When you hit the side of the bowl, you see waves in the Jell-O,” she said. “In the lab we put sprinkles on top, then put the bowl on a shaker. With the right frequency and a strobe, the waves appear to stand still. If the Jell-O is stiff, the waves are longer. If it is soft, the waves will be shorter. When they see the waves, it’s an ‘a-ha’ moment. We hope they go away with a better appreciation for how their brain can be injured inside the skull.”

Bayly also received a three-year, $395,000 grant from the NSF to measure the mechanical properties and processes that lead to motion in the cilia and flagella. Cilia are tiny eyelash-like hairs in the respiratory system, brain and reproductive system that beat together in a steady rhythm to sweep out bacteria and mucus. However, if the cilia don’t work together, don’t beat properly or at all, it can lead to a variety of disorders.

Bayly and his colleagues, including Susan Dutcher, PhD, professor of genetics and of cell biology and physiology at the School of Medicine; Jin-Yu Shao, PhD, associate professor of biomedical engineering; and Gang Xu, DSc, a former postdoctoral researcher in Bayly’s lab now an assistant professor at the University of Central Oklahoma, will team up to measure the mechanics in genetically modified flagella in algae that are close in structure and behavior to human cilia.

Their findings could lead to a better understanding of cilia and flagella, which will lend new insight into how they fail in disease and ultimately to new diagnostic tools or therapy.

Bayly and his colleagues will use a high-speed video imaging technique in Shao’s lab to get high-resolution images of the flagella waves, then analyze the images to estimate its forces through fluid.

“Dr. Shao has a system called an optical trap which uses a laser beam to pin a bead in fluid; it takes a force to move the bead away from the laser beam,” Bayly said. “We will use the flagella to grab onto the bead and try to move it. By seeing how much the bead deflects and how much the flagella deflects, we can get an idea of the stiffness of the flagella. We’re very lucky to have a collaborator with this equipment and expertise.”

Cilia move fluid through numerous passageways, making them critical to development, reproduction and preventing infection. But they move without a brain, Bayly said.

“That cilia conduct this autonomous behavior without a central nervous system is really quite astounding,” Bayly said. “The same mechanism that moves cilia in the airway also makes sperm swim. If we could recreate this in a manmade device, it could be very useful, especially if we were working on a nano- or micron scale. If we could understand this coordination scheme, the potential for harnessing it is fascinating.”

This project also will allow undergraduate students from Washington University and the University of Central Oklahoma to participate in summer research. Okamoto will work with these students to create an “axobot,” a large-scale model of the algae flagella, which are less than half a micron in diameter and about 10 microns long, or about the width of a red blood cell. Like waves in a bowl of gelatin, the large-scale model will help students visualize and explore how the flagella moves. 

Once created, the axobot will be used for demonstrations and activities in outreach programs, including Youth University, Explore Engineering and Women in Engineering Day. 

Shown are human breast cancer cells (red) growing amid mouse cells (green).

Breast cancer that spreads to other organs is extremely difficult to treat. Doctors can buy patients time, but a cure remains elusive. Now, researchers at Washington University School of Medicine in St. Louis have shown that human breast tumors transplanted into mice are excellent models of metastatic cancer and could be valuable tools in the search for better treatments.

According to new research published Sept. 19 in Cell Reports, these transplanted tumors maintain the genetic errors that caused the original cancer, even though they are growing in mice. As such, mice carrying human tumors can help identify drivers of tumor growth and serve as excellent test subjects for investigating new drugs.

Senior author Matthew J. Ellis, MD, PhD, said the paper is a step toward precision medicine, allowing researchers to study model tumors matched to a specific patient whose treatment regimens are well-documented.

“It is so powerful to have a model of Mrs. Jones’ cancer or Mrs. Smith’s cancer,” said Ellis, a breast cancer specialist who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University. “First, we have carefully documented information about the patient. We know exactly what drugs she responded to and what drugs she didn’t. Second, we have her consent for full genetic analysis. And third, we take the cells from her cancer and grow them in a special strain of mice that has no immune system, so they grow cells from a human without rejection.”

Ellis and his colleagues reported that the breast tumors growing in the mouse are startlingly similar to cancers growing in the human. And the changes that do occur in the transfer from human to mouse are often “silent,” having no effect on tumor growth.

“We are addressing a fundamental question about how similar or different the tumor is once it’s in a mouse,” said Elaine Mardis, PhD, co-director of The Genome Institute, which performed the sequencing. “These results give us confidence that pursuing new therapies using the mouse will provide an accurate picture of how that therapy will impact the tumor in the patient.”

The analysis showed that mutations occurring at high frequency in the original tumor remained at high frequency in the mouse. Likewise, and somewhat surprisingly, according to Ellis, less common mutations remained at the same low frequency in the mouse.

“A simple growth model says the slower-growing clones should go away,” Ellis said. “They shouldn’t be maintained at the same low frequency, but they are. And this drive for equilibrium is so strong it can survive crossing a species barrier. In maintaining this hierarchy, the genetically different clones in the tumor are interacting, a bit like different cell types within an organ, which is a wild thought because it means that our old models based on competition between the clones may be incorrect.”

Ellis emphasized that this approach is fundamentally different from most breast cancer research. Others have grown human tumors in mice, but Ellis’ team is the first to sequence whole genomes — the patient’s healthy genome, tumor genome and the corresponding mouse genome — to determine how closely the mouse tumor resembles that in the human. Others have tested new drugs in breast cancer cell lines growing in a dish, but these cell lines are far removed from any information about the original patient the cells were taken from and how that patient fared with a particular kind of treatment.

“We are trying to close the gap between what is happening in the clinic and what goes on in the laboratory,” said Ellis. “We learned that our system was mostly capturing rapidly growing, treatment-resistant lethal tumors, which is exactly what our studies should focus on.”

The approach also allowed the researchers to identify new mutations that appeared to be driving the strong drug resistance exhibited by these tumors. Specifically, they found mutations in the estrogen receptor.

“Research over the past 20 years has shown tantalizing hints that patients whose disease stops responding to anti-hormonal agents have changes in the estrogen receptor,” said Ellis. “And we found all three types of ‘gain-of-function’ mutations in the estrogen receptor gene ESR1 in the tumor samples.”

This study focused on estrogen receptor (ER) positive breast cancer — the most common type — that also is resistant to standard treatment. Unlike ER-positive cancers that respond well to treatment, those that are drug-resistant spread elsewhere in the body even with aggressive treatment.

Typically, ER-positive tumor growth is driven by the presence of estrogen. Block or remove the estrogen with different types of drugs, such as the commonly prescribed tamoxifen or aromatase inhibitors, and the tumor stops growing. Some women with estrogen receptor-positive breast cancer do extremely well on such anti-hormone treatment. But some don’t, and it’s not clear why.

Perhaps shedding light on this mystery, the researchers found three different types of mutations in the estrogen receptor in patients whose cancer was resistant to anti-hormone therapy. One type of mutation is called gene amplification, in which multiple copies of the ESR1 gene are present. A second type is point mutations in the part of the receptor that binds estrogen, causing the receptor to become active even without estrogen. And the third type was a translocation, in which half of the estrogen receptor gene was swapped for a completely unrelated gene from a different part of the genome.

Similar to the way breast cancer patients currently are told whether their tumors make estrogen receptor, Ellis envisions a clinical test that could tell a patient whether and how the estrogen receptor is mutated.

“We want to be able to make a diagnosis based on the specific tumor biology,” Ellis said. “For example, if we look at ESR1 and see amplification or point mutations or a translocation, we want to design clinical trials to determine whether we should give drug A, drug B or drug C.

“Our results are a good start for designing cures for metastatic breast cancer, which is a long-term goal for many of us who work with patients with stage 4 disease.”

This work was funded by grants to Matthew J. Ellis by Susan G. Komen for the Cure (BCTR0707808, KG090422 and PG12220321). The DNA sequencing and analysis were performed by The Genome Institute at Washington University School of Medicine and supported by grants to Richard K. Wilson from the National Human Genome Research Institute (NHGRI U54 HG003079). The tissue procurement core was supported by NCI 3P50 CA68438. The HAMLET Core was supported by CTSA grant UL1 RR024992. The RPPA analysis was supported by PO1CA099031, U54CA112970, KG081694 and P30 CA16672 to Gordon Mills. The RNA sequencing was supported by the TCGA Project (U24-CA143848), the NCI Breast SPORE program (P50-CA58223-09A1), and by the Breast Cancer Research Foundation to Charles Perou.

Li S, et al. Endocrine therapy resistant ESR1 variants revealed by genomic characterization of breast cancer derived xenografts. Cell Reports. Sept. 19, 2013. 

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.

Propofol is the most widely used intravenous general anesthetic in the world.

Until now, it hasn’t been clear how propofol connects with brain cells to induce anesthesia. The researchers believe the findings, reported online in the journal Nature Chemical Biology, eventually will lead to the development of more effective anesthetics with fewer side effects.

“For many years, the mechanisms by which anesthetics act have remained elusive,” explained co-principal investigator Alex S. Evers, MD, the Henry E. Mallinckrodt Professor and head of the Department of Anesthesiology at Washington University. “We knew that intravenous anesthetics, like propofol, act on an important receptor on brain cells called the GABA_A receptor, but we didn’t really know exactly where they bound to that receptor.”

Alex S. Evers/Nicholas P. Franks

Researchers used a photoanalogue of propofol to identify where it binds to GABA_A receptors. The small green circles on the left show the site.

Researchers have altered the amino acids that make up the GABA_A receptor in attempts to find propofol's binding site, but Evers said those methods couldn’t identify the precise site with certainty.

“In previous work to directly identify anesthetic binding sites, GABA_A receptors had to be extracted from membranes and purified prior to performing the binding studies,” he said. “Our method allowed us to study propofol binding to the intact receptor in its native membrane environment.”

Having developed the techniques to analyze the interactions between anesthetics and GABA_A receptors in their native environment, Evers’ laboratory teamed up with a group at Imperial College that had been taking the same approach. Led by Nicholas P. Franks, PhD, professor of biophysics and anaesthetics, the group has spent years creating a photoanalogue of propofol that both behaves in precisely the same way as propofol and contains a labeling group that permanently attaches to its binding site on the GABA_A receptor when exposed to a specific wavelength of light.

In creating the analogue of propofol, it’s as if the researchers put a tiny hook onto the molecule so that when it binds to the GABA_A receptor, it grabs onto the receptor and won’t let go.

Franks

Evers and Franks believe this technique has implications
beyond propofol and other anesthetics.

Evers

Using the techniques they have developed, Evers and Franks now plan to identify binding sites of other anesthetic agents. They believe their approach also can be used to study other types of drugs, such as psychiatric agents and anti-seizure drugs.

Funding for this research comes from the Medical Research Council, UK; the National Institute of General Medical Sciences (NIGMS) and the National Center for Research Resources of the National Institutes of Health (NIH); the Austrian Ministry of Science and Research and the European Seventh Framework Program.

NIH grant numbers PO1-GM47969, P41 RR00954 and UL1 RR024992.

Yip GMS, Chen ZW, Edge CJ, Smith EH, Dickinson R, Hohenester E, Townsend RR, Fuchs K, Sieghard W, Evers AS, Franks NP. A propofol binding site on mammalian GABAA receptors identified by photolabeling. Nature Chemical Biology, Advance Online Publication, Sept. 22, 2013.
10.1038/nchembio.1340

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.