Aris Melissaratos Photo: Sonja Kinzer

Johns Hopkins considers itself a world leader in knowledge creation. In the past two years, the university has done a good deal of business creation, too.

Aris Melissaratos, senior adviser to the president for enterprise development at Johns Hopkins since February 2007, said that from day one he’s been trying to change the culture here and make the university more entrepreneurial.

When he arrived, Melissaratos said, he encountered a faculty population that was somewhat adverse to self-promotion and the business side of technology creation.

“Commercialization had almost become a dirty word, and the prevailing thought was let’s not do anything to rock the research boat,” said Melissaratos, former secretary of Maryland’s Department of Business and Economic Development. “What I’ve been preaching is let’s get back to our roots and our prime mission, which is knowledge for the world. In that sense, it’s OK to be a little mercenary. Let’s do whatever we can to get the technology out there so it can help the world, while we never forget our institutional foundation of research excellence.”

The efforts have paid off.

Johns Hopkins in fiscal year 2008 spawned a dozen startup companies, seven of them based in Maryland, that collectively raised $76 million. This fiscal year, Johns Hopkins has already formed 10 companies, several of them dealing with medical devices or therapeutics that help fight infectious diseases and cancer.

The 22 companies founded in the past two years almost double the number in the preceding seven years, when the average was four companies started annually, with a high of six.

In his role, Melissaratos supervises the university’s Technology Transfer Office, the intellectual property administration center that serves Johns Hopkins researchers and inventors as a licensing, patent and technology commercialization office.

The move forward started when the Technology Transfer Office adopted the motto “Johns Hopkins is open for business” and began to reach out aggressively to the business community in new and innovative ways. Just before Melissaratos arrived, the office helped launch the Vine and Venture Series, a quarterly series of after-business-hours talks now held at the Rangos Building of the Science + Technology Park at Johns Hopkins in East Baltimore. The talks feature representatives of major companies who come to speak with faculty and staff on how to partner with those in the pharmaceutical, biotechnology and medical technology communities.

In June, the Technology Transfer Office co-hosted an inaugural Johns Hopkins Medicine Entrepreneurial Speed-Dating event in an effort to connect Johns Hopkins inventor scientists with entrepreneurs experienced in starting businesses. Organizers felt that such an event could accelerate the formation of new life science companies. By all accounts the event was a tremendous success, and it will be held next year.

Melissaratos and others highlighted the recent boon of startups at the annual meeting of the Johns Hopkins Alliance for Science and Technology Development, which Melissaratos now chairs. The Alliance, founded in 2004, is a 40-member committee charged with evaluating the commercial viability of selected research projects at the university. Members of the Alliance—venture capitalists and research and development executives from the pharmaceutical and biotechnology industries—evaluate marketing opportunities and provide assistance with the identification of financing to enable the commercialization of worthy discoveries.

The Alliance last year partnered with the University of Maryland to greatly expand the annual fall conference, held last week on Johns Hopkins’ Mount Washington campus. The two-day event drew nearly 190 people and allowed Johns Hopkins faculty the opportunity to present their inventions in 30-minute blocks to an audience full of colleagues, venture capitalists, biotechnology investors and local business leaders.

The meeting also featured updates on recent startups and a presentation by Barbara Slusher and Jeffrey Rothstein, faculty members in the School of Medicine’s Neurology Department, about the Brain Science Institute’s new NeuroTranslational Program. The program was created with the mission of identifying and creating new drug therapies for neurological disorders, based on JHU faculty research.

Melissaratos said that much has been accomplished over the past two years to transport the benefits of Johns Hopkins discovery to the world.

“In the past, we have been criticized in some quarters for not being commercial enough or getting good results, but we’re turning that around,” he said. “Universities like Stanford and MIT have a legacy of starting lots of companies. We’re catching up. Events like the Entrepreneurial Speed-Dating help get the word out that we are easy to do business with and have expertise in many areas.”

Melissaratos said that his office has also been training faculty to make more effective business presentations. Under the direction of Helen Montag, corporate relations manager, and with the volunteer help of Michael Rosen, senior vice president for new business development at Forest City Enterprises’ Science & Technology Group, a training program has helped more than 100 faculty and staff by coaching them on effective marketing pitches to attract potential investors. The results, he said, can be lucrative.

Technology transfer revenues have grown steadily from $9 million in fiscal year 2006 to $12.2 million in 2008. And Melissaratos said that he expects this growth to continue. He credits the leadership of Wesley Blakeslee, Technology Transfer executive director; Glen Steinbach, administrative director; Keith Baker, portfolio director; and a “superb” staff of licensing professionals.

What’s next? Melissaratos said that he wants to work more with interdisciplinary centers such as the Center for Biomedical Innovation and Design, the Institute for NanoBioTechnology, the Center for Computational Medicine, the Brain Sciences Institute and the Institute for Basic Biological Sciences.

Since 2000, 86 percent of the startup companies have been in the fields of therapeutics, medical devices and diagnostics. Melissaratos said he would like to expand technology transfer in the areas of information technology, engineering and the physical sciences. The “open for business” sign, he said, should be on everyone’s door.

For more information on the Technology Transfer Office, go to its new Web site at techtransfer.jhu.edu.

Also: See Aris Melissaratos speak at the recent TEDx MidAtlantic conference.

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A new display in the Newton H. White Athletic Center pays tribute to the 114 members to date of Johns Hopkins’ Athletic Hall of Fame. Photo: Jay Vanrensselaer

The accomplishments of Johns Hopkins’ student-athletes never looked so good.

Recent visitors to Homewood’s Newton H. White Athletic Center would undoubtedly have noticed the attractive new displays in the building’s lobby that commemorate the 114 members of Johns Hopkins’ Athletic Hall of Fame and the university’s 35 NCAA postgraduate scholarship recipients.

The elegant two-sided displays feature etched black Plexiglas plaques that appear to float on a clear Plexiglas sheet. The Hall of Fame plaques are engraved with images of a Johns Hopkins Blue Jay, the university seal, the name of the student-athlete and his or her sport(s), class and induction year.

The predominantly blue displays also feature fabric banners with images of JHU athletes in action.

The two 17-by-14-foot displays, which were installed late last month, were created by Marketechs Exhibit Design, based in York, Pa. Marketechs also created the Academic All-American Wall located in the hallway off the main lobby.

The displays are viewed as phase one of an effort to transform the building’s lobby into a museum space, according to Mike Renwick, the university’s associate director of athletics.

“We wanted to honor those who came before us and highlight the great tradition of Johns Hopkins athletics,” Renwick said. “Everyone knows we have a really deep lacrosse tradition, but those who walk through the lobby now can see that we have a broad-based athletic program with excellence in many sports.”

In phase two of the project, to be completed next summer, all of the existing wall display cases will be refurbished and seven new cases fashioned to prominently feature all the varsity sports. The cases will include photos, trophies, ribbons, historical facts and other elements. A centerpiece “champions case” will be created to highlight Johns Hopkins’ current conference championship and national championship winners.

The existing Hall of Fame room will be renovated in the final phase of the project. It will become a student-athlete lounge. “We’re going to spruce the room up and give it a more athletic feel,” Renwick said.

The Johns Hopkins Athletic Hall of Fame was formed in 1994, and up to nine new members are inducted each year.

The prestigious NCAA Postgraduate Scholarship was created in 1964 to promote and encourage postgraduate education by rewarding the National Collegiate Athletic Association’s most accomplished student-athletes. The NCAA awards up to 174 postgraduate scholarships—a one-time grant of $7,500 to pursue graduate studies—annually to student-athletes who excel academically and athletically and who are in their final year of intercollegiate athletics competition.

Johns Hopkins men’s swimmer John Kegelman was the most recent recipient of the scholarship award. The mechanical engineering major, who received the award last May, had a 4.0 cumulative GPA and was a two-time captain for the men’s swim team and earned All-America honors five times in his career.

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Lucier is a former chairman and CEO of Invitrogen Corp., which in 2008 merged with Applied Biosystems to form Life Technologies. The company is one of the largest providers of systems, biological reagents and related services, supplying life science technologies to scientists worldwide.

During Lucier’s tenure at Invitrogen, the company was recognized four years in a row by the Life Science Industry Awards, which are given to leading life science suppliers. Invitrogen’s Qubit platform, which in 2007 received the prestigious R&D 100 Award as one of the most technologically significant products of the year, was one of many company innovations recognized by the industry.

Lucier was named the North American Drug Discovery Technologies CEO of the Year in 2009 by Frost & Sullivan, which also named Life Technologies the Company of the Year. PharmaVOICE magazine recognized Lucier as one of 2007’s 100 Most Inspiring People in the pharmaceutical and biotechnology industries, and in 2006 the Penn State College of Engineering presented him with its World-Class Engineer Alumni Award.

Under Lucier’s guidance, Invitrogen developed a robust philanthropy program dedicated to science education and promoting scientific literacy. In 2008, the company formed the Invitrogen Foundation (now the Life Technologies Foundation), focused on promoting the critical role science plays in society.

From 2000 to 2003, Lucier was president and CEO of General Electric Medical Systems Information Technologies.

Lucier, who received his bachelor’s degree in engineering from Pennsylvania State University and his MBA from Harvard Business School, serves on the boards of directors of the Biotechnology Industry Organization and the Burnham Institute for Medical Research. He is also a distinguished lecturer at San Diego State University.

The Leaders & Legends monthly breakfast series, which features today’s most influential business and public policy leaders, is designed to engage business and community professionals in an examination of the most compelling issues and challenges facing society today.

Admission to the lecture, which includes breakfast, is $35. To register and for more information, go to carey.jhu.edu/leadersandlegends.

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Kerry Stewart and his team are embarking on two studies addressing some of the nation’s biggest health problems: obesity, diabetes and cardiovascular health. Photo: Will Kirk

Everyone knows that a healthy diet and adequate exercise are effective weapons in the battle against obesity and type 2 diabetes.

But do such regimens have the same positive impact on our cardiovascular system? People assume so and scientists think so, but—perhaps surprisingly—they don’t know for certain.

“People are surprised when they hear that there really is very little data on the topic of whether diet and exercise, which are already recommended for treating obesity and diabetes, will also benefit cardiovascular health,” said Kerry Stewart, a professor of medicine in the Johns Hopkins University School of Medicine and director of Clinical and Research Exercise Physiology at Johns Hopkins Bayview Medical Center. “The evidence that exercise and a healthy diet in people with these conditions help the cardiovascular system is just not in yet.”

In an effort to pin down the facts, Stewart and his team are embarking on two studies investigating whether the cardiovascular health of people who either have diabetes or are at risk of developing diabetes because they are overweight and sedentary shows improvement after the adoption of a healthy diet and exercise regimen. The cost of the studies—about $1.5 million for each—is underwritten by the federal stimulus package through the National Institutes of Health.

“These two projects address some of our nation’s biggest public health problems: obesity, diabetes and cardiovascular health,” said Stewart, who recently presented groundbreaking data that revealed, among other things, that weekly bouts of moderate aerobic exercise on a bike or treadmill, or a brisk walk, combined with some weightlifting may cut down levels of fat in the liver by up to 40 percent in people with type 2 diabetes.

Stewart’s investigations are among the more than 300 stimulus-funded research grants totaling more than $148 million that Johns Hopkins has garnered since Congress passed the American Recovery and Revitalization Act of 2009 (informally known by the acronym ARRA), bestowing the National Institutes of Health and the National Science Foundation with $12.4 billion in extra money to underwrite research grants by September 2010. The stimulus package—which provided $550 billion in new spending, including the above grants, and $275 billion in tax relief—is part of President Barack Obama’s plan to kick-start a stagnant economy by doling out dollars for transportation projects, infrastructure building, the development of new energy sources and job creation, and financing research that will benefit humankind.

As of this month, Johns Hopkins scientists have submitted nearly 1,300 proposals for stimulus-funded investigations ranging from strategies to help recovering addicts stay sober and the role that certain proteins play in the development of muscular dystrophy to mouse studies seeking to understand how men and women differ in their response to the influenza virus.

Stewart’s studies, each of which will last six months, will examine the cardiovascular effects of exercise and diet on overweight and obese people with type 2 diabetes or at risk for developing diabetes, and on people with abdominal obesity, which puts them at a higher-than-average risk of several early markers for cardiovascular disease, including endothelial function, arterial stiffness and dysfunction of the heart’s ability to fill with blood. The first study will enroll about 76 participants and will ascertain whether a diet alone or a diet plus exercise has a more positive impact on cardiovascular health. The second study will enroll the same number of subjects and will compare whether a low-carbohydrate diet plus exercise is better for cardiovascular health than is a low-calorie, low-fat diet plus exercise.

“We expect our subjects to become more fit, lose weight and lower their blood sugar,” Stewart said. “What we don’t know is if these changes will also lead to improved cardiovascular health and ultimately—and this is key—the prevention of cardiovascular disease. If our results are positive, this would provide further and convincing evidence about the role of diet and exercise as a vital pathway to heart health.”

This is part of an occasional series on Johns Hopkins research funded by the American Recovery and Revitalization Act of 2009. If you have a study you would like to be considered for inclusion, contact Lisa De Nike at lde@jhu .edu.

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The U.S., Canadian and Italian scientists say that they have identified three changes in the chemical makeup of desmin—a key structural protein—in heart muscle cells in dogs. The changes led to the formation of debrislike protein clusters, or amyloidlike oligomers containing desmin, in heart muscle, similar to the amyloid plaques seen in the brain tissue of Alzheimer’s patients. The protein alterations, which were reversed by surgically repairing the heart, occurred at the onset of heart failure. Further experiments found the same chemical modifications to desmin in the heart muscle of four people already diagnosed with the disease.

Misshaped desmin proteins and amyloidlike debris had been reported in 2005 in mice genetically altered to develop chronic heart failure, providing the first biological link between the two chronic diseases. Studies since have also reported desmin changes in failing animal hearts, but none detailed what the chemical changes were or how they might affect organ function.

Researchers say that their latest analysis, presented Nov. 15 at the American Heart Association’s annual Scientific Sessions in Orlando, Fla., is believed to be the first to tie common underlying structural changes in desmin to malformations observed in the heart as it weakens, strains to pump blood and starts to fail. Their results are also believed to be the first to suggest that toxic, desminlike amyloids could form in response to stress placed on the heart.

“Our study leads us to believe that desmin plays a key role in heart failure,” said lead study investigator Giulio Agnetti, a protein biochemist. “Now we have a chemical target to research further and help us investigate what could be the underlying biological cause of heart failure and if it is, like Alzheimer’s, an amyloid-related disease.

“Just as significantly, our study raises the prospect of testing new treatment options for heart failure by moving beyond treating symptoms of the disease and getting to the root of the matter, preventing these desmin amyloids from forming and impairing heart function from the start,” continued Agnetti, a postdoctoral research fellow at both the Johns Hopkins School of Medicine and its Heart and Vascular Institute, and the University of Bologna and its National Institute for Cardiovascular Research, in Italy. Symptoms of heart failure may include fatigue, shortness of breath and enlargement of the heart.

The team’s latest investigation began with an analysis of proteins contained in heart tissue samples collected from a group of dogs whose hearts had been surgically altered to beat irregularly, become stressed and fail. Additional tissue samples were taken from a group of healthy controls.

Researchers compared these samples, looking for structural and chemical changes in desmin, which is found in all heart muscle cells and is a key component of the intermediate filaments that make up the scaffolding, or muscle cell support structure. This is the same muscle structure, they say, that becomes disorganized in heart failure.

The team’s analysis yielded at least three chemical differences in each desmin protein in response to heart failure. Further tests showed that phosphate molecules had attached at two spots within the protein’s structure. They also found accumulating amyloidlike debris, containing desmin, in the damaged heart tissue.

When researchers performed surgery restoring the dogs’ heart pumping function to normal, they found that phosphorylated sites mostly reverted to normal. The amyloidlike oligomers also began to disappear. Tissue samples from four people with heart failure showed similar desmin modifications.

Senior study investigator Jennifer Van Eyk said that it is “not surprising” that these changes in the so-called “scaffolding” structure of the heart can produce toxic debris. “But what is most interesting about our findings is that we have shown that these chemical changes and debris are related to impaired heart function, which, ultimately, may explain how and why the heart can fail,” said Van Eyk, a Johns Hopkins professor and director of Hopkins’ NHLBI Proteomics Group and the Proteomics Center at Johns Hopkins Bayview Medical Center, where the protein analysis took place.

Researchers next plan to analyze each of the desmin modifications to determine the subsequent biological impact of each chemical change.

Agnetti points out that the team’s protein analysis was made possible only in the last 15 years, with the development of technologies for detailed chemical analysis, such as mass spectrometry and gel electrophoresis. Previously, he said, scientists had focused mostly on genetic changes and their relationship to disease, as opposed to disease-causing alterations to proteins that occur after proteins are made.

Some 5.7 million American men and women suffer from chronic heart failure, which caused an estimated 290,000 deaths in 2005. A majority of sufferers have high blood pressure, the leading risk factor for the disease.

Funding support for this study was provided by the National Heart, Lung and Blood Institute and Compagnia San Paolo di Torino, in Italy.

The Johns Hopkins NHLBI Proteomics Group is one of 10 centers funded as part of the United States’ seven-year program dedicated to the study of proteomics and understanding the functions of proteins in the development of cells, tissues and organisms, in both normal and disease processes.

In addition to Agnetti and Van Eyk, Johns Hopkins researchers who took part in this study were Victoria Halperin-Kuhns, Yurong Guo, Simon Sheng, Zongming Fu, David Kass and Gordon Tomaselli. Also involved in the analysis were Francesco Nicolini and Tiziano Gherli, both of the University of Parma; and Carlo Guarnieri and Claudio Caldarera, both of the University of Bologna.

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The Carey Business School will occupy four floors of the Legg Mason Tower in Harbor East. Photo: Phil Sneiderman

The Johns Hopkins Carey Business School is moving to the new Legg Mason Tower at 100 International Drive in Baltimore’s Harbor East.

The university has entered into a lease agreement with Legg Mason and H&S Properties, the developer of Harbor East, that will give the business school about 80,000 square feet of space on four floors.

The state-of–the-art waterfront Legg Mason building will house classrooms, student space and offices for the dean, the faculty and staff. The space will be ready in time for the start of the fall 2010 semester, when the school will welcome its inaugural full-time Global MBA class. The new location, officials said, will provide the school with a teaching and learning facility appropriate for full-time, executive and part-time business programs.

“We are delighted to be able to contribute to this vibrant part of the city and to do so in a facility that will provide a stimulating and nurturing learning experience for all our students,” said Yash Gupta, dean of the Carey Business School.

The move to the Legg Mason building is a major step in the school’s plan to be one of the nation’s premier business schools, drawing upon Johns Hopkins’ strengths in science and research and taking a distinctive approach of interdisciplinary collaboration with the university’s other academic divisions.

At the Legg Mason Tower, the Carey Business School will occupy space on the first, second, 12th and 13th floors. The first floor will serve as the entrance to the school. The second will contain classrooms, breakout spaces for students and faculty, group study rooms, a library and offices for student organizations. The 12th and 13th floors will house offices for the dean, faculty and staff.

The agreement gives the university options to extend the initial lease term of 10 years up to an additional 10 years. The lease also provides the school with access to the building’s cafeteria and parking garage.

The Carey Business School also offers courses at satellite locations in Washington, D.C., and in Columbia and Rockville, Md. The school will continue to hold classes at these locations after the move to Harbor East.

The school has an enrollment of about 1,740 full- and part-time students and employs 30 full-time faculty, 110 part-time faculty and 80 staff members. Eighty students are expected to arrive in August 2010 for the new full-time Johns Hopkins Global MBA program.

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This program is the first in a discussion series titled Shaping the Future that will address the most challenging issues in education.

Panel members on Dec. 7 are Martha Kanter, undersecretary of education, U.S. Department of Education; Nancy Grasmick, Maryland state superintendent of schools; Andres Alonso, CEO of Baltimore City Public Schools; Joe Hairston, superintendent of Baltimore County Public Schools; Robert Slavin, director of the Center for Research and Reform in Education at Johns Hopkins; James McPartland, director of the Center for Social Organization of Schools at Johns Hopkins; and Mariale Hardiman, former Baltimore City public school principal and chair of the Department of Interdisciplinary Studies at the School of Education.

RSVPs can be submitted online at www .education.jhu.edu/shaping-future.

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In a study published Nov. 9 in the Archives of Internal Medicine, researchers found that just 13 percent of service members who left their units with back pain as their primary diagnosis eventually returned to duty in the field. Women, officers, those deployed in Afghanistan and those with previous back pain had better outcomes but only marginally. Aside from combat injuries sustained during battle, the return-to-duty rate for spinal pain and other musculoskeletal disorders is lower than for any other disease or noncombat injury category except for psychiatric illness, the researchers said.

“The whole mission of the medical corps for the military is to preserve unit strength, to keep people doing what they’re doing,” said study leader Steven P. Cohen, associate professor of anesthesiology at the Johns Hopkins School of Medicine and a colonel in the U.S. Army Reserve. “If you have only a 13 percent success rate, this is a failure. There’s a systemic problem.”

Cohen and his team looked at data from 1,410 soldiers who were medically evacuated out of war zones complaining chiefly of back pain from 2004 through 2007. More than 95 percent of the service members were taken to the U.S. military’s treatment facility in Landstuhl, Germany. Researchers assessed how many were returned to their stationed units within two weeks and how many were sent to the United States unable to perform their duties.

A previous study done by Cohen, who is also director of chronic pain research at Walter Reed Army Medical Center, showed that when soldiers with back pain were taken to a pain clinic in Iraq, all patients returned to their units. When they were sent to pain clinics in Germany or in Washington, D.C., fewer than 2 percent did. Both this previous study and the new research suggest that the farther away evacuees are treated, the less likely they are to return to their units. Cohen noted that it can be difficult for certain soldiers to return to their jobs, particularly those in physically demanding combat-related roles. “It’s the rule in war: People will have back pain because you have to go on these long road marches and carry heavy equipment, wear body armor,” he said. “The roads are not paved. Riding in these vehicles while wearing body armor, it hurts your back.”

Cohen said that the reason why few military personnel return to their units after leaving with back pain may simply be a reflection of the outcomes for back pain in civilian life. “Back pain has notoriously low success rates for treatment,” he said.

The biggest predictors of a poor outcome, he said, are psychosocial factors. People who are depressed or anxious, cope poorly with stress, are unhappy in their jobs or have psychological issues are more likely to remain disabled by back pain. Cohen said that those with back pain who remain in the country where they are deployed may be more motivated to stay on the job or are more satisfied with their role in the military.

The military needs to find a way to get soldiers with back pain back to their units wherever possible, said Cohen, suggesting that could be accomplished if there were more pain management options in Iraq or Afghanistan, following the model used for soldiers with symptoms of combat stress. When those symptoms are treated at mental health clinics on base, approximately 95 percent of service members returned to their units. When treated in a transitional unit in nearby Kuwait, the figure was around 50 percent. When sent to Germany, fewer than 10 percent returned.

Other researchers on the study are Shruti G. Kapoor, a resident in the Department of Anesthesiology at the Johns Hopkins School of Medicine; Maj. Conner Nguyen, chief of Physical Medicine and Rehabilitation at Landstuhl Regional Medical Center in Germany; and Col. Leslie Foster and Maj. Anthony Plunkett, both of Walter Reed Medical Center.

The research was funded in part by a congressional grant from the John P. Murtha Neuroscience and Pain Institute, Johnstown, Pa.; the U.S. Army; and the Army Regional Anesthesia & Pain Medicine Initiative, Washington, D.C.

Related Web site: Steven P. Cohen

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“Oftentimes we are surprised that a drug known to do something else has another hidden property,” said Jun Liu, a professor of pharmacology and molecular sciences at Johns Hopkins and author on the study published Oct. 1 in the Proceedings of the National Academy of Sciences.

In this case, the surprise is a big one. The drug acriflavine, used in the 1930s for treating gonorrhea, has turned out to have the previously unknown ability to halt the growth of new blood vessels. Preliminary tests showed that mice engineered to develop cancer had no tumor growth if treated with daily injections of acriflavine.

“As cancer cells rapidly divide, they consume considerable amounts of oxygen,” said Gregg Semenza, the C. Michael Armstrong Professor of Pediatrics and director of the vascular program at the Johns Hopkins Institute for Cell Engineering. “To continue growing, a tumor must create new blood vessels to deliver oxygen to the tumor cells.”

Acriflavine stops blood vessel growth by inhibiting the function of the protein hypoxia-inducible factor, or HIF-1, which was discovered by Semenza’s team in 1992. When HIF-1 senses that the surrounding environment is low in oxygen, it turns on genes necessary for building new vessels. Though essential for normal tissue growth and wound healing, HIF-1 is also turned on by cancers to obtain the oxygen they need to survive. Most important, in order for HIF-1 to work, two subunits must bind together like puzzle pieces.

Most drugs are unable to prevent protein binding because the drug molecules can be much smaller than the proteins with which they interact. A medicine must hit just the right spot, a critical domain or pocket on the surface of one protein, to stop it from binding to another protein. Even though drugs that stop binding are uncommon, they are such an effective means to stop protein function that Semenza decided to look for one that might block HIF-1. To do that, he turned to the Johns Hopkins Drug Library, a collection of FDA- and internationally approved compounds that was assembled by Liu.

To visualize protein binding, scientists engineered a cell line so that when the HIF-1 subunits came together, they would cause the cell to light up like a firefly. They then tested each of the more than 3,000 drugs in the drug library in hopes of finding one that would turn out the light. Acriflavine did, and further studies confirmed that it was binding directly to HIF-1.

“Mechanistically, this is the first drug of its kind,” Liu said. “It is acting in a way that is never seen for this family of proteins.”

Liu said he hopes that acriflavine can one day be incorporated into chemotherapy cocktails, one drug among many that help fight cancer.

Johns Hopkins is seeking even more new uses for old drugs. So far, drugs in the library have been screened for use against malaria, tuberculosis, HIV and the Ebola virus. In the future, Liu expects even more researchers to take advantage of the library, which is continuing to grow.

“In the public domain, Hopkins has the largest drug library,” Liu said. “The more drugs you have, the more possibilities, the higher the chance you rediscover something that will help.”

This study was funded by the Johns Hopkins Institute for Cell Engineering and the Foundation for Advanced Research in the Medical Sciences.

Authors on the paper are Kang Ae Lee, now of Princeton University; and Huafeng Zhang, David Z. Qian, Sergio Rey, Liu and Semenza, all of Johns Hopkins.

Related Web sites

Institute for Cell Engineering

Gregg Semenza

‘PNAS’

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Prompted by growing concern that the increase was due to decreased physical activity associated with increased TV viewing time and other sedentary behaviors, researchers examined the patterns and time trends in physical activity and sedentary behaviors among U.S. adolescents based on nationally representative data collected since 1991. The review found signs indicating that the physical activity among adolescents increased while TV viewing decreased in recent years. The results are featured in the Oct. 30 online issue of Obesity Reviews.

“Although only one-third of U.S. adolescents met the recommended levels of physical activity, there is no clear evidence they had become less active over the past decade while the prevalence of obesity continued to rise,” said Youfa Wang, senior author of the study and an associate professor with the Bloomberg School’s Center for Human Nutrition and the Department of International Health. “During the recent decade, U.S. adolescents had greater access to TV, but significantly fewer of them watched TV for three or more hours per day. In addition, daily physical education attendance rates improved along with the use of physical education class in engaging in physical activity. However, there are considerable differences in the patterns by age, sex and ethnicity.”

Wang, along with co-authors Shiru Li, former visiting scholar with the Center for Human Nutrition, and Margarita Treuth, adjunct associate professor with the Center for Human Nutrition and a professor with the University of Maryland East Shore, examined findings from the nationally representative Youth Risk Behavior Surveillance surveys from 1991 to 2007. The surveys included U.S. high school students in grades nine through 12 and provided information about their physical activities, including enrollment and participation in physical education in school and sedentary behaviors including screen time. Based on these surveys, researchers examined the patterns and time trends and compared the observed physical activity patterns with the national goals set in Healthy People 2010, a comprehensive agenda for improving the health of all Americans. They found that minority students were less likely to be physically active and more likely to engage in sedentary behaviors than white students. Girls were less active than boys, and decreased physical activity was related to an increase in age.

“The large gaps between the 2007 achievement and the 2010 targets indicate that the goals are unlikely to be achieved by 2010,” Wang said. “Our study suggests that more vigorous efforts are needed to help young Americans engage in adequate regular physical activity and reduce sedentary behaviors, which will help promote good health. In addition, these findings may suggest factors other than physical activity and sedentary behaviors, such as unhealthy eating, may play a more important role to help explain the recent increase in obesity.”

The research was supported in part by research grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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