New Drug Target Identified for Fighting Parkinson's Disease

Researchers at Johns Hopkins' Institute for Cell Engineering (ICE) have discovered a protein that could be the best new target in the fight against Parkinson's disease since the brain-damaging condition was first tied to loss of the brain chemical dopamine.

Over the past year, the gene for this protein, called LRRK2 (pronounced "lark-2"), had emerged as perhaps the most common genetic cause of both familial and unpredictable cases of Parkinson's disease. Until now, however, no one knew for sure what the LRRK2 protein did in brain cells or whether interfering with it would be possible.

Now, after studying the protein in the lab, Johns Hopkins researchers report that the huge LRRK2 protein is part of a class of proteins called kinases and, like other members of the family, helps control other proteins' activities by transferring small groups called phosphates onto them. The researchers also report that two of the known Parkinson's-linked mutations in the LRRK2 gene increase the protein's phosphate-adding activity. The findings appear in the current (Nov. 15) issue of the Proceedings of the National Academy of Sciences.

"We know that small molecules can interfere with this kind of activity, so LRRK2 is an obvious target for drug development," says Ted Dawson, M.D., Ph.D., co-director of the Neural Regeneration and Repair Program within ICE and a leader of the study. "This discovery is going to have a major impact on the field. It's going to get people talking about kinase activity."

Because kinases affect a number of other proteins, LRRK2's link to Parkinson's may be a result of either its own activity or a shift in the activities of one or more "downstream" proteins.

"The next step is to prove that LRRK2 overactivity results in the death of brain cells that produce dopamine, the defining pathology of Parkinson's disease, and to figure out how it does so," says Dawson, who cautions that the large size of the LRRK2 gene and protein could make clinical application of the Hopkins discovery years away.

"For example, we would want to isolate the active part of the LRRK2 protein and use that more manageable part to screen for molecules that would block its activity. But what takes us a second to think of could take four or five months to do," says Dawson. "These things may not come as fast as the field wants."

The LRRK2 protein, sometimes called dardarin, is 2,527 building blocks long. In contrast, the alpha-synuclein protein, the first to be linked to Parkinson's disease, is only 140 building blocks long. The parkin protein, linked to more cases of familial Parkinson's disease than any other to date (although LRRK2 is likely to break that record), is considered "big" at 465 building blocks long.

Undaunted by the size of the LRRK2 gene and protein, Andrew West, Ph.D., a postdoctoral fellow and co-first author of the paper, spent months extracting the full-length gene from human brain samples and developing reliable experiments to test how mutations affected LRRK2's activity. Co-first author Darren Moore, Ph.D., also a postdoctoral fellow, built the tools to get bacteria to make mounds of LRRK2 protein and two mutant versions and also tracked down the LRRK2 protein's location inside cells.

The research team's experiments showed that the LRRK2 protein, in addition to its role as a kinase, actually sits on mitochondria, cells' energy-producing factories, where it likely interacts with a complex of proteins whose failure has also been implicated in Parkinson's disease.

Mutations in LRRK2 were first tied to Parkinson's disease in 2004 and to date explain perhaps 5 percent to 6 percent of familial Parkinson's disease (specifically so-called autosomal dominant cases, in which inheriting a single faulty copy of the gene results in disease) and roughly 1 percent of Parkinson's disease in which there is no family history. But few of the gene's genetic regions have been analyzed in depth.

"As researchers comb through the rest of the LRRK2 gene, it seems likely that more mutations will be found and that it will be tied to more varieties of the disease," says Dawson.

What's known about LRRK2 so far suggests that it might connect diseases long thought to be distinct, particularly Parkinson's disease and conditions known as "diffuse Lewy body disease," named for the bundles of certain proteins that build up inside cells in the brain in affected people. As a result, studying LRRK2 might improve understanding of and eventually treatment for more than just Parkinson's disease itself, Dawson says.

The research was funded by the National Institute of Neurological Disorders and Stroke, the Lee Martin Trust, the Sylvia Nachlas Trust, the National Parkinson Foundation and the American Parkinson's Disease Association.

Authors on the paper are Andrew West, Darren Moore, Saskia Biskup, Artem Bugayenko, Wanli Smith, Christopher Ross, Valina Dawson and Ted Dawson, all of Johns Hopkins. Valina Dawson is co-director of the Program in Neuroregeneration and Repair of the Institute for Cell Engineering at Johns Hopkins.

On the Web:
http://www.pnas.org


Magnetic Probe Tracks Implanted Cells in Cancer Patients

By using MRI to detect magnetic probes of tiny iron oxide particles, an international research team for the first time has successfully tracked immune-stimulating cells implanted into cancer patients for treatment purposes.

"In four of the eight patients, MRI revealed that the implanted cells weren't where they needed to be to be effective for treatment," says Jeff Bulte, Ph.D., an associate professor of radiology at Hopkins' Institute for Cell Engineering who developed methods to optimally label cells with the clinically approved iron oxide particles.

This new application of the probes -- already clinically approved for MRI scanning of the liver -- could dramatically improve efforts to test and use cellular therapies such as vaccines to treat cancer or prevent its recurrence or stem cells to repair damaged organs, say the researchers.

Bulte and a team of Dutch researchers used MRI and a magnetic probe approved by both European and U.S. agencies to locate therapeutic cells injected into eight melanoma patients.

"Our results show that the MRI-based technique was more accurate than tracking the cells using radioactivity and that ultrasound failed to accurately guide injection of the cells into lymph nodes in half of the patients," says Bulte, an author on the report, which appears in the November issue of Nature Biotechnology.

The cells used in the current study, so-called dendritic cells, are the immune system's own "most wanted posters" because they take up and display foreign proteins that tell the immune system's fighters what cells to look for and destroy.

Since the mid-1990s, clinical trials have been testing dendritic cells to see whether they can stimulate the immune system to kill cancer cells. In these trials, dendritic cells from patients are exposed to proteins from the patients' cancer cells and then returned to the patients.

However, some of the clinical trials of such "cancer vaccines" have been disappointing, with some patients responding very well but others not at all. A critical issue behind each patient's success on the treatment, however, is whether the cells get to the lymph nodes, where the immune system's fighters are normally "trained" by dendritic cells. Until now, there's been no accurate way to know where the cells end up.

It's thought, but not proven, that the best way to get the cells where they need to be is to inject them directly into the lymph nodes that drain the area containing a tumor. Currently, doctors use ultrasound to guide the needle, and dendritic cells carrying a radioactive tag are sometimes used to try to double-check the cells' final resting place.

However, in this study, the Dutch team discovered that using MRI and iron oxide particles was able to track the cells' location much more accurately than the radioactive tracking method and provided anatomic detail simultaneously -- structural detail not possible by tracking radioactivity.

"On the MR images, we can see the lymph nodes, and we can see the magnetically labeled dendritic cells, and we can tell very clearly whether they are in the same place," says the study's first author, Jolanda de Vries, an assistant professor at the Nijmegen Center for the Molecular Life Sciences (NCMLS) of the Radboud University Nijmegen Medical Center in The Netherlands. "The cells can't get from the fat into the lymph nodes by themselves, so injecting them properly is very important."

Bulte says he, Dara Kraitchman, Ph.D., D.V.M., and colleagues at Hopkins are already testing magnetically labeled stem cells with MRI-compatible injection systems to allow MRI guidance of injection in large animals.

The current clinical trial builds on Bulte's earlier work tracking magnetically labeled cells in animals. Four years ago, he and colleagues reported that stem cells containing so-called magnetodendrimers could be followed by MRI.

But to advance to clinical trials, the research team switched from the experimental magnetic tags to formulations of iron oxide already approved for clinical use in Europe (as Endorem) and the United States (as Feridex). Because immature dendritic cells naturally take up materials around them, they simply absorbed, or ingested, the iron oxide particles when exposed to them in the lab. The magnetically labeled, cancer-primed cells were then returned to the patients, all of whom had stage III melanoma.

"Although dendritic cell therapy is used in clinical trials to treat patients with melanoma, in this study we wanted to see whether the magnetically labeled cells could be tracked by MRI, to study their migratory behavior in more detail," says Carl Figdor, principal investigator of the study, of the NCMLS. "We were very pleased that they showed up clearly. With the anatomic information from the MRI, we could see precisely where they were -- inside or outside of the lymph nodes."

The research was funded by The Dutch Cancer Society, the Netherlands Organization for Scientific Research, the Dutch Program for Tissue Engineering, the TIL-foundation and the NOTK-foundation. Bulte is supported by the United States National Institute of Neurological Disorders and Stroke.

Scientists Uncover "Tags" that Force Proteins to Cell Surface

Johns Hopkins scientists have discovered internal "shipping labels" that allow -- and perhaps force -- hundreds if not thousands of proteins to get to the surface of cells and stay there. Two natural proteins that use one of these "tags" are the ion channel that lets heart cells contract on cue, and the docking point that allows HIV, the virus that causes AIDS, into cells, the researchers discovered.

Because proteins on the cell surface are "lock-on" sites for drugs and other molecules, as well as triggers of immune reactions, the findings, described in the Sept. 11 advance online publications of Nature Cell Biology, might revolutionize efforts in drug and vaccine development, says the Hopkins team.

"A typical step in drug development is to get cells in a dish to express the protein you want to target with drugs, and then to test thousands of molecules to see which ones interact with the protein and have the effect you want," says the study's senior author, Min Li, Ph.D., a professor of neuroscience at the High Throughput Biology Center of the Johns Hopkins' Institute for Basic Biomedical Sciences.

"But if you can't get the protein to the cell surface, you can't use this screening technique. If we can force proteins to the cell surface, we can overcome obstacles that have prevented laboratory study of some really important proteins," says Li. The application of these surface tags to force protein transportation to the cell surface is the subject of a Patent Cooperation Treaty (PCT) patent application submitted by The Johns Hopkins University.

From among 25 billion randomly created, eight-building-block-long protein bits, postdoctoral fellow Sojin Shikano uncovered 65 that forced a normal protein to leave the cell's protein-building factory and go to the cell surface. By searching sequences of known human proteins, the researchers then identified those that use variations of the most potent tag they'd found, dubbed SWTY, shorthand for the four building blocks at the end of its protein sequence -- serine, tryptophan, threonine and tyrosine, in that order.

"This particular tag and its closest relatives actually mark normal proteins for delivery to the cell surface," says Li. "In some diseases, a protein that should be on the cell surface isn't, and in the lab, sometimes it's proven impossible to get a protein to the cell surface in order to study it. The tags we've found might help us force proteins to the surface, which offers real hope for overcoming these hurdles."

Laboratory studies in which the tags might be used to force a protein of interest to the cell surface are likely to be widely used fairly quickly, but Li cautions that any potential clinical applications will require understanding exactly how the tag helps the protein's transportation.

Among the "problem proteins" are those that detect odors in the nose, and the protein that's faulty in cystic fibrosis. Being able to force these to the cell surface in laboratory dishes might enable identification of more potent scents or ways to help people who can't smell, or help uncover new strategies for treating CF.

Although many scientists would say that failure to get these proteins to the cell surface means the proteins weren't assembled properly in the cell, Li says that how and where proteins are made has a lot to do with the difficulties researchers have had.

For one, proteins are made deep inside the cell; the genetic instructions for building proteins are in the cell nucleus, and proteins are assembled in a nearby "factory" in the cell. Also, scientists have long known that proteins prefer to stay put in this factory, the endoplasmic reticulum, unless they contain specific transportation instructions, much like an internal shipping label.

To figure out what tiny sequences might label the protein for delivery to the cell surface, Shikano added randomly generated eight-building-block long tags onto one end of a particular protein. He then evaluated whether the protein ended up on the cell surface instead of remaining inside the cell. The researchers found three major classes of such tags, grouped according to similarities in their sequences of building blocks, and delved into the most potent of them.

By using a computer program developed by graduate student Brian Coblitz to probe proteins' sequences, the researchers discovered that, by fairly stringent criteria, roughly 4 percent of all human proteins contain SWTY or a very close relative. The eight-block-long tag itself is part of the so-called C-terminal end of these proteins, and its existence helps explain why some engineered proteins don't go where they're supposed to go, Li says.

"If you remove a small part of the very end of a protein, it seems unlikely to disrupt how the rest of the protein folds in a three-dimensional structure, but that's what most scientists think goes wrong if a protein doesn't go to the surface," says Li. "But now we know the problem might just be a faulty transportation signal."

Given that proteins can be thousands of building blocks long, the final eight building blocks may not seem to be very important. But Li chose this size to study in part because naturally occurring proteins were already known to use similar-size bits for recognition and signaling.

"The immune system uses ones that are seven to nine blocks long to identify viral proteins or other immune triggers," explains Li.

Also, the number of possible combinations of eight-block-long protein segments provides a "reasonable number" to sort through -- 25 billion or so -- given today's high throughput technologies. To make it even easier, Shikano developed a system that would separate the wheat from the chaff before the analysis began -- if the protein wasn't taken to the cell surface by the tag, the cell died.

"If the protein went to the cell surface, the cell was in the mix, and if the cell wasn't there to be analyzed, we knew we didn't want it anyway," says Li.

Authors on the paper are Shikano, Coblitz, Sun, and Li. The researchers were funded by the National Institute of General Medical Sciences, the National Institute of Neurological Diseases and Stroke and the American Heart Association.

On the Web:
www.nature.com/ncb


Mutations in Cancer Cells Suggest New Forms of Treatment

Researchers at Johns Hopkins and J. Craig Venter Institute in Rockville, Md., helped identify three new genetic mutations in brain tumors, a discovery that could pave the way for more effective cancer treatments.

The researchers discovered DNA abnormalities in two tyrosine kinase proteins already known to disrupt normal cell activity and contribute to tumor formation.

The discovery of these mutations is especially significant, the researchers say, because tyrosine kinases can be targeted using pharmaceuticals.

"We picked these proteins to sequence because receptor tyrosine kinases sit on the cell surface where anticancer drugs can get at them," said Gregory J. Riggins, M.D., co-lead author of the study and an associate professor in the Department of Neurosurgery at The Johns Hopkins University School of Medicine.

In the study, the researchers identified two of the previously unknown mutations in fibroblast growth receptor 1 (FGFR1) and one in platelet derived growth factor receptor alpha (PDGFRA).

FGFR1 and PDGFRA, said Riggins, have been implicated in several other cancers, such as colorectal, breast and ovarian cancer, as well as chronic myelogenous leukemia, gastrointestinal stromal tumors and lymphoma.

Hopkins researchers chose cells from 19 glioblastoma tumor samples from eight females and 11 males ranging in age from 7 to 77 years. Glioblastomas are malignant tumors of the central nervous system usually found in the cortex of the brain. The cells were sent to Venter Institute's Joint Technology Center, where researchers led by co-author Robert L. Strausberg, Ph.D. used high-throughput gene sequencing equipment to resequence 20 targeted proteins.

Researchers discovered the mutations after comparing the resequenced genes with corresponding genes from the human genome sequence.

A previous study by Hopkins researchers, led by Victor Velculescu, M.D., Ph.D., used high-throughput gene sequencing to identify 14 mutated genes that have potential links to the growth of colon cancer cells, according to Riggins. These discoveries suggest potential future therapies that might use small molecules and antibodies to regulate the function of the mutated genes.

The success of that study prompted researchers to take the same approach to search for new drug targets for glioblastoma, a brain tumor for which current therapies are weak.

According to Riggins, the recent advances in genomic information and technology have set the stage for the assembling of a complete catalog of molecular alterations that contribute to cancers. Genes involved in the tyrosine kinase family will be important in these future studies because they play a significant role in signaling between cancer cells and what's around them. Combined with the remarkable clinical success doctors have had with the molecular targeting of this family of genes, Riggins said, these new findings could result in effective new treatments for cancer.

"The next step," he added, "is to find inhibitors of these mutations and find out how we can reverse the effects of these mutations in the cancer cell. Our hope is that we can target enough of these mutations to treat the cancer."

Funding for this study was provided by Ludwig Trust, the Children's Cancer Foundation, the Irving J. Sherman Research Professorship and J. Craig Venter Science Foundation.


Key Protein Linked to Transverse Myelitis and Multiple Sclerosis

Hopkins researchers have discovered a single molecule that is a cause of an autoimmune disease in the central nervous system, called transverse myelitis (TM), that is related to multiple sclerosis.

In a study published in the October issue of The Journal of Clinical Investigation, psychiatrist Adam Kaplin, M.D., Ph.D., an assistant professor at The Johns Hopkins University School of Medicine, and neurologist Douglas Kerr, M.D., Ph.D., also an assistant professor at Hopkins, showed that the levels of the protein, IL-6, are dramatically elevated in the spinal fluid of transverse myelitis (TM) patients.

Although the majority of TM patients suffer a single attack, 15 percent to 30 percent of patients go on to develop full-blown MS. TM evolves rapidly and without warning and usually results in permanent impairment, including weakness of the legs and arms, bowel and bladder dysfunction, pain and paralysis.

IL-6 is a chemical messenger that cells of the immune system use to communicate with one another. One of the cell types injured by high levels of IL-6 includes oligodendrocytes, which help produce the protective myelin sheath coating around nerve cells. The findings offer one possible mechanism responsible for demyelinating disorders, such as TM and MS, and may aid in the development of effective therapies against these disorders, the researchers say.

"This is the first time a single culprit has been identified as causing a CNS autoimmune disease," said Kaplin.

The researchers began investigating the protein IL-6 when they became aware that TM patients suffered from memory impairment and depression. IL-6 has been implicated in mood and concentration disorders.

"This discovery is a success story that begins with listening carefully to what patients are telling us about their suffering and then collaborating across disciplines to open up new avenues of investigation," said Kaplin.

"TM is related to other autoimmune disorders of the nervous system, including Guillain-Barré syndrome, MS and acute disseminated encephalomyelitis. This study may give us a foothold in understanding all of these disorders and how they are linked together. The benefit is, therefore, not only to those who are paralyzed by TM, but to those who have disabilities due to a variety of autoimmune disorders. We are actively using these findings to aid in developing future diagnostic, prognostic and therapeutic advancements," said Kerr, director of the Johns Hopkins Transverse Myelitis Center, the only center devoted to TM in the world.

Researchers analyzed 42 inflammatory proteins in the cerebrospinal fluid of both TM and healthy patients. They found that IL-6 was consistently elevated in TM patients' spinal fluid. Further, the level of IL-6 directly correlated with the severity of paralysis.

Using cell culture and animal studies, the researchers confirmed that elevated IL-6 levels were directly injurious to the spinal cord. They showed that spinal fluid from TM patients induced death of spinal cord cells when cultured in a dish and that IL-6, when infused in adult rats, induced paralysis. Under the microscope, tissue from IL-6-infused rats showed demyelination and injury of axons, pathology that was nearly identical to that seen in human patients with TM.

Kerr and Kaplin also deduced that the reason IL-6 elevations injure only the spinal cord and not other regions of the nervous system was because distinct regions of the nervous system have different responses to IL-6. They concluded that these different types of responses might be a part of why different autoimmune disorders of the nervous system affect distinct regions and cause distinct symptoms.

"When we started, we knew nothing about the bad players in this drama in the spinal cord of CNS autoimmune diseases – it was a classic murder mystery and we set out together to find out ‘who done it'," said Kaplin. "We've answered who could have done it, and how, and where."

Funding for this study was provided by the National Institutes of Health.

Rise in Hospital Noise Poses Problems for Patients and Staff

Announcements blare from overhead speakers. Electronic devices beep. Heating and cooling systems rumble. Employees and visitors speak loudly.

This sound snapshot, researchers say, comes not from a factory or a sports stadium but from a typical hospital. In a new study, Johns Hopkins University acoustical engineers found that hospital noise levels internationally have grown steadily over the past five decades, disturbing patients and staff members, raising the risk of medical errors and hindering efforts to modernize hospitals with speech recognition systems. Some studies even indicate that excessive noise can slow the pace of healing and contribute to stress and burnout among hospital workers.

During a two-year research project, acoustics experts Ilene Busch-Vishniac and James E. West learned that hospital noise is among the top complaints of both patients and hospital staff members, but that little is being done to address the problem. The researchers found that scientific studies of hospital noise were scarce, and that most had been conducted by medical personnel, not acoustical engineers.

"That told us this problem was important enough that the doctors and nurses were willing to step outside their comfort zone to make some noise measurements, even though they didn't always know how to analyze the data correctly," Busch-Vishniac said. "Acoustical engineers needed to get involved, and it was long overdue. We believe that funding is needed to broaden fundamental research in this area."

Added West: "People have been complaining about hospital noise for years, but little has been done about the problem."

In 2003, when Stephanie L. Reel, vice president and chief information officer for Johns Hopkins Medicine, called their attention to noise levels in the pediatric intensive care unit at Johns Hopkins Hospital, Busch- Vishniac and West agreed to investigate. The researchers surveyed the handful of published reports on hospital noise from the past half-century and made their own sound measurements in several patient areas at Johns Hopkins. The Baltimore hospital, which provided financial and staff support, also allowed Busch-Vishniac and West to test two techniques that helped reduce noise in some patient areas.

What made their work so different from past research was that it partnered the medical professionals and the acoustical engineers, first to characterize the hospital sound environment and then to find ways to lessen the impact of sound.

"This study focused on a very real challenge," Reel said. "A noisy intensive care unit introduces patient, family and staff dissatisfaction. It has also been reported that noise can contribute to lapses in short-term memory, which could then introduce safety concerns. Ilene and Jim recognized the importance of this issue and worked with us to address the immediate needs of this pediatric intensive care unit. They also gave us terrific recommendations for the new clinical buildings that will be constructed over the next few years."

The researchers believe their findings have important implications for hospitals worldwide. West and Busch- Vishniac presented their conclusions at the annual meeting of the Acoustical Society of America, held recently in Minneapolis. A paper based on their work will appear in an upcoming issue of the Journal of the Acoustical Society of America. West and Busch-Vishniac are both past presidents of the society. At Johns Hopkins University, Busch-Vishniac is a professor of mechanical engineering. West is a research professor in the Department of Electrical and Computer Engineering. He also is a member of the National Academy of Engineering.

Following are some highlights from their study:

Since 1960, average daytime hospital sound levels around the world have risen from 57 decibels to 72; nighttime levels have jumped from 42 decibels to 60. All of these figures exceed the World Health Organization's 1995 hospital noise guidelines, which suggest that sound levels in patient rooms should not exceed 35 decibels. The measurements vary little among different types of hospitals, indicating the problem is pervasive.

Much of hospital noise falls in the human speech frequency range, making oral communication more difficult. This can force doctors and nurses to speak even louder to be heard, further boosting the noise level. Sound congestion could lead to a misunderstanding of spoken orders for tests and medication, the researchers said. In addition, many hospitals are moving to more automated systems, in which equipment responds to voice commands. But amid a clutter of sound in the human voice frequencies, voice recognition software does not work well.

In many hospital units, noise does not take a break at sunset. Measurements made by Busch-Vishniac and West indicated that noise levels remain high around the clock. This was attributed partly to hospital ventilation systems that run at powerful settings and to a proliferation of alarm-laden electronic devices.

Can anything be done to reduce hospital noise? Although the problem is complex, the Johns Hopkins acoustics experts obtained modest reductions by making two small changes in patient areas.

In the pediatric intensive care ward, hospital personnel were paged an average of every five minutes via overhead loudspeakers. Busch-Vishniac and West introduced the staff to small hands-free personal communicators, worn on a lanyard. The communicators operate like cell phones, and each staff member can be signaled directly and quietly. This system cut the frequency of overhead pages to about once an hour. The system was initially used during a two- month trial run, but staff members were so pleased by the results that the hospital purchased the system for that unit.

The researchers also found that acoustical ceiling tiles, a common sound-absorbing furnishing, are often absent from patient areas because they can provide a hiding place for infectious organisms. To address this concern, Busch-Vishniac and West wrapped fiberglass insulation inside an anti-bacterial fabric, then attached these sound- absorbers to the ceiling and walls of a cancer unit at Johns Hopkins Hospital. This measure suppressed some sounds that previously bounced around the room. "Our treatment reduced the reverberation time by almost a factor of three," West said.

Hospital staff members were pleased by the reduction in noise. "We could not have done this without their expertise as acoustical engineers," said Sharon Krumm, administrator and director of nursing for the Kimmel Cancer Center at Johns Hopkins Hospital. "They understood this as a patient safety issue. Their expertise is what made the whole outcome possible."

Although these tactics were successful, West cautioned that "the majority of hospital noise problems, particularly involving the air handlings systems, are not that easy to fix." He and Busch-Vishniac said long-range solutions will require that skilled acoustics experts and architects work closely together to reduce noise problems when planning future hospitals and renovations of existing medical centers.

Funding for this research was provided by The Center for Quality Improvements and Patient Safety of Johns Hopkins Hospital.


Hopkins Establishes Center for Clinical Global Health Education

The Johns Hopkins University School of Medicine has established a new center designed to provide clinical training to health care providers in parts of the world where resources and infrastructure are limited or lacking. Called the Center for Clinical Global Health Education (CCGHE), the new operation aims to use advanced telemedicine technology and Hopkins experts to provide clinical training to health care workers around the world in an efficient and cost-effective manner.

"Recently, many donors have made it possible to obtain HIV/AIDS medications for some of those infected adults and children in resource-limited settings," says Robert Bollinger, M.D., M.P.H., director of the new center. "Unfortunately, these medications help only a fraction of these infected populations. These countries lack experienced, trained health care providers to dispense the drugs effectively and safely. Professionals need to be properly trained, and that's where the center can help."

So far, more than 50 different countries have expressed interest in the Center's programs. As one of its first projects, the CCGHE will initiate an intensive, interactive HIV training program at the BJ Medical College in Pune, India, this November. It will include more than 20 live telemedicine lectures by JHU faculty for frontline Indian physicians. The CCGHE has also started specialized clinical education programs in Ethiopia and the Congo and will facilitate clinical research collaboration among participating institutions in these countries.

"We are very happy to collaborate with the CCGHE," says Alexander Nason, director of the Johns Hopkins Office of Telemedicine and director of Johns Hopkins Interactive. "Telemedicine and Web-based learning tools provide easy and relatively affordable ways to create links between Hopkins and international care providers."

Initially funded by The Johns Hopkins University School of Medicine, the CCGHE plans to maintain operations through donations from individuals and companies in the United States and abroad.

For more information, please visit the Center for Clinical Global Health Education (CCGHE) at www.ccghe.jhmi.edu.


CME COURSES

December 10-11, 2005
Eleventh Annual Pain Medicine Update
Johns Hopkins University School of Medicine, Turner Bldg.
Baltimore, MD

December 16, 2005
Fluoroscopy Credentialing Conference
Johns Hopkins University SOM, Thomas B Turner Building, Baltimore, MD

December 17, 2005
16th Annual Neurology for the Primary Practitioner and First Annual Neurology for the Neurologist
Renaissance Harborplace Hotel
Baltimore, MD