CDI investigator Christina Gurnett examines a 3-week-old patient with familial idiopathic clubfoot. Gurnett seeks to understand the genetic causes of this birth defect. The baby's uncle was born with the same condition.

CDI Executive Director Alan Schwartz also is the Harriet B. Spoehrer Professor of Pediatrics and Children's Hospital's Pediatrician-in- Chief.

CDI Scientific Director Jonathan Gitlin joins a group of children in announcing the launch of the institute.

The goal is ambitious: to attack childhood's most devastating diseases. The methods are innovative and equally ambitious: "We mean this to be one of the most visionary partnerships in pediatric medicine." So says Jonathan D. Gitlin, scientific director of the newly launched Children's Discovery Institute (CDI), a novel collaboration between the School of Medicine and St. Louis Children's Hospital to fund research and speed cures in four areas of childhood maladies: congenital heart disease, cancer, lung diseases, and muscular and skeletal defects.

Initial funding matches the CDI's lofty goal: some $120 million in private donations, which, Gitlin believes, will lead to further National Institutes of Health funding. The CDI's first research grants to investigators in the University's schools of Arts & Sciences and Medicine, totaling some $5 million, were awarded in early 2007.

"Our goal is to conduct research in a way that has never been done anywhere else on behalf of children," says Gitlin, the Helene B. Roberson Professor of Pediatrics.

"We're pulling together people with unique skills who've never worked together. We're asking them to explore a problem in a new, interdisciplinary way that completely leverages the intellectual capital of this University."

For example, one newly funded project studying the potential of nanoparticles in treating pediatric brain cancers brings together researchers across a spectrum of disciplines, including chemistry, biology, medicine, and biomedical engineering. Such cross-specialty scientific collaboration is designed to stir innovation and find more creative paths to cures.

In addition to funding multidisciplinary investigative teams, CDI grants will support faculty recruitment, research fellows, and unique educational initiatives. The CDI's first faculty recruit, epilepsy specialist Christina A. Gurnett, assistant professor of neurol- ogy and pediatrics, will use her award to start her own laboratory here.

Some $5.3 million in annual funding is being used to recruit eight to 10 scientists to the four centers comprising the CDI: the McDonnell Pediatric Cancer Center, the Center for Mus-culoskeletal Diseases, the Center for Pediatric Pulmonary Disease, and the Congenital Heart Disease Center.

Other research initiatives include studying the fetal origins of metabolic disorders and the correlation between low birth weight and coronary heart disease, hypertension, stroke, and type 2 diabetes later in life; investigating the genetic factors in the development of congenital heart disease; exploring the genetic basis of pleuropulmonary blastoma family cancer syndrome; and more. The CDI's executive director Alan Schwartz, the Harriet B. Spoehrer Professor of Pediatrics and Children's Hospital's Pediatrician-in-Chief, holds high hopes for the institute's potential to crack mysteries in dread childhood diseases.

"This is an extraordinarily exciting time and opportunity for both our institutions--Washington University and St. Louis Children's Hospital--to galvanize the resources that exist and direct those to discovering the basis and approaches to curing major children's health issues," Schwartz says.

Gitlin agrees. "It lies within our grasp in the next quarter of this century to rid ourselves of a lot of childhood diseases," Gitlin says, "and that's the greatest hope as a pediatrician I have for my patients."

Nanoparticles may revolutionize diagnosis, treatment of diseases

(left) Samuel Wickline, professor of medicine, and Gregory Lanza (right), associate professor of medicine and of biomedical engineering Below: Nanoparticles have an inert core coated with a layer of active components--homing agents, imaging substances, or drugs. Here, the particles (blue) are engineered to target strings of fibrin in a blood clot.

A revolution in the way cancer, heart disease, and other serious illnesses are diagnosed and treated is under way, fomented by an army of molecule-size particles that can hunt down, latch on to, expose, and subdue enemies in the body. That is, if the dreams of Samuel Wickline and Gregory Lanza come true--along with those of the National Cancer Institute, which has bet $16 million on their nanotechnology research.

"We're trying to change the way drugs are delivered to make them safer and more effective at the site of tumors," says Wickline, professor of medicine. And this means injecting patients with designer nanoparticles--1/400th the width of a human hair--that carry imaging and/or therapeutic agents through the bloodstream to tumors, arterial blockages, or other diseased areas that they'll adhere to. It's worked on laboratory animals. Now Wickline and Lanza are ready to test it on humans.

The technology holds significant promise for cancer treatment, Lanza says, where chemotherapy drugs often harm much more than the tumor they're attacking.

"We don't like the fact that cancer treatment can be as horrific as the disease," says Lanza, associate professor of medicine and of biomedical engineering.

Wickline says that the ability to target drugs to affected areas via their technology could greatly reduce dosages. "And if you can give 10 or 100 times less drug over the course of chemotherapy, you'll have less toxicity," he says. "We've entered an era of precisely targeted and individualized cancer therapy."

The technology also can be used to fight other dread diseases, such as arteriosclerosis, says Wickline, a cardiologist. A company formed by him and Lanza to help see that their nanoparticles reach the treatment pipeline more quickly, Kereos Inc., is developing a nanoparticle therapy to fight artery-clogging plaque, which often causes heart attacks and strokes.

Pre-clinical, animal-based trials are slated for 2008. But human trials, which can cost hundreds of millions of dollars, will require partnering with a large pharmaceutical company. Kereos already has built collaborations with Phillips Medical Systems and Bristol-Myers Squibb Medical Imaging.

"Washington University and Kereos are working to ensure that this technology reaches its fullest potential to help patients suffering from a broad spectrum of diseases," Lanza says.

Finding could suggest potential therapies in fight against obesity

Jeffrey I. Gordon

The good news: School of Medicine researchers have learned that leaner people have an abundance of a particular intestinal bacterium.

The bad news: There's still no known substitute for diet and exercise to control weight.

However, their findings could suggest potential therapies in the fight against obesity.

Jeffrey I. Gordon, director of the Center for Genome Sciences and the Dr. Robert J. Glaser Distinguished University Professor of Molecular Biology and Pharmacology, and his students recently published research findings in two papers that appeared in the journal Nature. Their first paper focused on obese mice.

Gordon explains, "Sequencing the genes in the microbial communities of their guts using a new method known as 'metagenomics' revealed that obesity was associated with a shift in proportional representation of the two major groups of bacteria in the intestine--the Bacteroidetes and Firmicutes--and an increase in the capacity of the community to harvest calories from common complex dietary carbohydrates known as polysaccharides."

Moreover, Gordon says, transplantation of the gut community from obese mice to sterile germ-free mice produced a greater increase in fat stores than did transplantation of a gut community from lean donors.

In their second paper, they showed that the shift in the two major groups of gut bacteria also occurred in obese humans.

"Our studies imply that differences in our gut microbial ecology help determine how many calories we are able to extract and absorb from our diet and deposit in our fat cells," Gordon says.

However, he warns: "The amount of calories you consume by eating and the amount of calories you expend by exercising are the key determinants of your tendency to be obese or lean."

Nonetheless, Gordon says, these studies raise some interesting questions: "Are some adults predisposed to obesity because they start out with fewer Bacteroidetes and more Firmicutes in their guts? Can features of a reduced-Bacteroidetes Firmicutes-enriched microbial community become part of our definition of an obese state or a diagnostic marker for an increased risk for obesity?

Answering those questions could lead to significant headway in fighting the global obesity epidemic. They also represent the opening round in a new area of bio-science: namely, understanding how humans are a mix of microbial and human cells and that our genetic landscape and physiology is an amalgamation of microbial and human genes, and microbial and human metabolic attributes.

The National Institutes of Health recently announced that as part of its "Roadmap" program, microbial genes now will be the subject of a second human genome project--one that is targeted to our "microbiome," Gordon says.

"Stay tuned, the results of this Human Microbiome Project promise to provide us with new appreciation of the foundations of our health, of our predispositions to various diseases, and how our changing lifestyles and world are affecting a dimension of human evolution we normally don't consider: our 'microevolution.'"

Teenager first to play video game using brain waves only

?This team, from left, Daniel Moran, Matthew Smyth, Eric Leuthardt and Nick Anderson, enabled a 14-year-old to play a two-dimensional video game using signals from his brain

The ability of a 14-year-old St. Louis-area epilepsy patient to accurately play a video game simply by thinking about it could lead to brain control of artificial limbs in paralyzed patients or amputees.

While that day lies in the future, Washington University researchers already have demonstrated the power of imagination in unique research and uncovered hidden secrets of the brain.

To trace the source of epileptic seizures, neurosurgeon Matt Smyth had implanted electrocorticographic grids on the teenage patient's brain. With his and his parents' approval, two University researchers, Eric C. Leuthardt and Daniel W. Moran, connected the grid to a sophisticated computer system that translated the patient's brain activity into joystick commands of the classic video game, Space Invaders, and prompted the teen to move the game's cannons by imagining their movement.

"He learned almost instantaneously," says Leuthardt, assistant professor of neurological surgery. "We then gave him a more challenging version, and he mastered two levels there playing only with his imagination."

Getting subjects to move objects using only their brains suggests the possibility of constructing biomedical devices that might control, say, a prosthetic arm or leg by imagining its movement.

Two years earlier, Leuthardt and Moran led a team that was the first to perform this research on four adult patients. "The ability to record from the surface of the brain in awake humans was key to our success," says Moran, assistant professor of biomedical engineering. "We knew that if we could get the recording electrodes very close to the brain, we would be able to capture novel, high-frequency information."

The subjects learned to control objects using this new high-frequency signal much faster than other recording modalities. "Doing this is a win-win situation, both for science and the child," Leuthardt says. "We devised this to be enjoyable and entertaining while we get groundbreaking information on the brain."

Center strives to build knowledge, improve lives of Latino families

Luis H. Zayas, professor of social work and of psychiatry, confers with Allyson Pilat, project assistant at the Center for Latino Family Research.

As Latinos become an increasingly important part of the American social fabric, research is still needed on their cultures, family, and their children's developmental challenges. Luis H. Zayas is working to change that.

The professor of social work has established the Center for Latino Family Research, the only such center in a U.S. school of social work investigating Latino social health, mental health, and family and community development, both here and in Latin America. The center's ultimate goal is to help improve the lives of Latino families in all of the Americas by building knowledge.

"Despite increasing scholarship on Hispanics in the United States, we still don't know enough about their health needs and the social and economic development of their families and communities," says Zayas, the Shanti K. Khinduka Distinguished Professor of social work and professor of psychiatry at the School of Medicine.

Under his direction, the center will produce family-oriented research on Latinos both in the United States and their countries of origin, and develop young scholars committed to advancing knowledge on Latino populations throughout the hemisphere.

"The effects of globalization have never been more evident," Zayas says. "A research center devoted to Latino families must be Pan-American in scope--the ties that bind are deep. What affects one country affects its neighbors."

Zayas points to his own research on U.S.-born Latina teenage suicide attempts--double that of other American teens--as an example of the family-oriented scholarship that will be undertaken by the center.

"We know that the adolescent's struggle for identity often clashes with her deep regard for family, its traditions, and beliefs. Until we understand the cultural conflict," Zayas says, "we will not be able to prevent this."

Hope Center equips scientists tackling neurological diseases

(above) Mark P. Goldberg (below) David M. Holtzman

"If you build it, they will come," says Director Mark P. Goldberg of the Hope Center for Neurological Disorders, taking a line from the film Field of Dreams. And come they have, perhaps even beyond Goldberg's dreams.

Some 400 scientists from 16 University departments now collaborate and share research results and facilities to speed potential treatments and cures for widespread neurological disorders--ALS (amyotrophic lateral sclerosis or Lou Gehrig's disease), Alzheimer's and Parkinson's diseases, cerebral palsy, spinal cord injuries, stroke, and more--thanks to the newfound lab cluster established just three years ago.

The Hope Center--which brings together scientists from the schools of Medicine, Engineering, and Arts & Sciences--strives to fast-track neurological research projects too timely to idle while waiting for federal funding, which often takes two or more years, says Goldberg, professor of neurology and of anatomy and neurobiology.

"Most scientists who have discovered a new gene or protein don't have the expertise or the funding to investigate using animal models," Goldberg says. "So a big part of what we are doing is to provide the animal disease models and the tools that they need to find new therapies."

The collaborative research model comes from the conviction that many neurological disorders share common molecular mechanisms of nerve-cell degeneration, according to Goldberg. Thus, fundamental discoveries related to one disease can quickly lead to treatment in others.

The National Institutes of Health (NIH) agrees. In fall 2006, the NIH awarded the Washington University neuroscience community and the Hope Center a five-year $8.3 million grant for the development of core facilities to support translational neuroscience research. Investigators in the Hope Center also were awarded a $6 million grant to fund an innovative, multidisciplinary stroke research program. They supplement significant NIH grants to the center's individual investigators.

"Washington University has long been an international leader in nervous system science," Goldberg says, "so this is the ideal setting for a new approach to brain diseases."

The Hope Center grew out of a collaboration between the School of Medicine and Hope Happens, founded by the late Christopher Wells Hobler, who, in 2001 at age 35, was diagnosed with ALS, an incurable neurodegenerative disorder that also had attacked his grandfather. Before he died, Hobler, the father of three, started a foundation to find a cure.

A member of the Hope Happens board of directors, David M. Holtzman, head of the Department of Neurology and the Andrew B. and Gretchen P. Jones Professor of Neurology, recently won the 2007 MetLife Foundation Award for Medical Research in Alzheimer's disease. His study of the buildup of amyloid plaques in the brain, a hallmark of Alzheimer's, could lead to earlier treatment, and exemplifies the sort of breakthrough research that is carried out at the Hope Center, as well as through many interactions at the Alzheimer's Disease Research Center.

One of Holtzman's projects seeks new methods of identifying Alzheimer's patients before dementia occurs.

Says Goldberg: "We are working together to look at diseases that affect millions of Americans" --some 50 million with permanent neurological disabilities that limit them, and with no effective treatments available.

Discoveries by Hope Center faculty already are leading to clinical trials of new therapies for patients with ALS, and Parkinson's and Alzheimer's diseases.