Longitudinal Study of Rural Cavity Prevention Programs
Richard Niederman has received a five-year grant of $6.6 million from the National Institute on Minority Health and Health Disparities for a project focused on improving oral health outcomes and reducing costs of rural school-based cavity prevention programs. This project, which uses comparative effectiveness and quality improvement methods, will examine rural school-based cavity prevention programs throughout the United States, with participating sites in Maine, Vermont, Kansas and Colorado.
Although cavities are a preventable infection, 10 million U.S. elementary school children (more than 25%) have untreated dental decay. The percentage is double for rural and Medicaid populations, and for racial and ethnic minorities. Importantly, untreated cavities have long-lasting detrimental educational, medical and social effects.
Preventive interventions with demonstrated efficacy in clinical trials are available and recommended by the Centers for Disease Control and Prevention. However, they are not routinely employed in a standard fashion, and are rarely evaluated for clinical or cost effectiveness. Hence, rural caries prevention programs employ varying intervention protocols with few effectiveness measures. The absence of effectiveness data risks program extinction when agencies examine their health budgets.
The objective of Dr. Niederman’s research is to evaluate, compare, and improve rural elementary school-based caries prevention programs using both clinical and cost effectiveness outcome measures. His hypothesis is that comprehensive prevention is more clinically and cost effective than incremental prevention. The programs in this study currently offer care to approximately 10,000 children, in 67 Title 1 elementary schools, in ten rural counties, in four states.
The Bertarelli Program in Translational Neuroscience and Neuroengineering
Six Groundbreaking Research Projects in Translational Neuroscience
In five of the six inaugural research projects of the Bertarelli Program, basic scientists and physicians at HMS will be working with EPFL (École Polytechnique Fédérale de Lausanne) bioengineers to create new methods to diagnose and treat a wide range of hearing loss afflictions, from those that are genetically based to those caused by damage from excessive noise. A sixth project will build on novel research on spinal cord stimulation done in Switzerland, taking it a step further by implementing stretchable electronics directly on the spinal cord and attempting to rebuild severed connections through stem cell regeneration therapy.
Seeing how we hear: imaging inside the ear
One of the great challenges in diagnosing hearing problems is that the physician cannot see the tissues and cells of the inner ear. In recent years, microendoscopes have been used experimentally to try to image the cells of the inner ear, but these rely on adding fluorescent dyes, something not practical for human diagnosis. At the same time, physicists have developed methods for imaging without dyes. For this project, a physicist from EPFL will collaborate with an HMS otologic surgeon to develop new imaging methods for the human inner ear. The researchers will use mouse and human inner ear tissue to optimize these new detection methods, learning, for instance, how to look through bone with long-wavelength light. Through imaging inner ear cells in animal models, they will set the stage for eventual clinical trials.
Konstantina Stankovic, HMS assistant professor of otology and laryngology, Massachusetts Eye and Ear Infirmary
Demetri Psaltis, professor of optics and Dean of the School of Engineering, EPFL
Gene therapy targets inherited deafness
About one in a thousand children are born with some form of hearing loss, often caused by inheritance of a mutant gene. For over ten years, researchers have looked to correct a variety of inherited disorders with gene therapy, a process in which genetically engineered viruses carry corrective genes into cells affected by a mutant gene. Some early failures diminished gene therapy’s promise, but new trials in humans have been remarkably successful and have raised hopes for conditions such as hearing disorders. A problem for gene therapy is that there are few viruses known to enter the inner ear’s sensory hair cells. A pioneer in use of viruses for hair-cell physiology from HMS and Children’s Hospital Boston and an EPFL expert in gene therapy for humans will collaborate to explore new viruses to carry genes into hair cells. Through restoring sensory cell function in mice with gene mutations that mimic human deafness, the researchers will attempt to correct inherited deafness in a live mouse. This research may clear a path for developing similar tools to restore hearing function in humans.
Jeffrey R. Holt, HMS associate professor of otology and laryngology, Children’s Hospital, Boston
Patrick Aebischer, professor in the Neurodegenerative Studies Laboratory and President, EPFL
Treating deafness through regeneration
Much of the hearing loss that affects older people is caused by the death of sensory cells and neurons in the inner ear, a consequence of loud noise, infection, or certain drugs. This is often accompanied by tinnitus, an incessant sense of ringing in the ears. Unfortunately, these sensory cells do not regenerate they way skin or blood cells do. A first step in treating this hearing loss is to learn how to regenerate inner-ear sensory cells and neurons. Harvard scientists have recently learned how to isolate cells from a developing inner ear and to genetically reprogram them to proliferate into millions in a dish. The challenge now is to turn them into sensory cells and nerve cells. An HMS world expert in inner ear development will work closely with an exceptionally creative bioengineer from EPFL. By investigating molecular changes that occur in inner ear cells when they proliferate, and then using a micro-engineered screening platform to test thousands of compounds simultaneously, the researchers will seek to find factors that convert proliferating cells into hair cells or neurons. Finally, these factors will be tested in mice that are deaf from genetic or environmental causes.
Lisa Goodrich, associate professor of neurobiology, HMS
Matthias Lutolf, assistant professor, Interfaculty Institute of Bioengineering, EPFL
Delivering drugs to treat hearing loss?
Once scientists learn to regenerate sensory cells in the laboratory, it is still a huge leap to make this happen in a human patient. The right drugs or chemical factors must be delivered to the inner ear, held in the right place, and released slowly over months, all without damaging the delicate sound-sensing structures. In this project, a pioneer in hair-cell regeneration from HMS will work with an EPFL bioengineer specializing protein engineering and nanotechnology techniques to develop new ways of delivering regenerative factors to the inner ear. Bound to hydrogels or packaged in novel “polymersomes” the factors will be taken up by the remaining cells, and will reprogram them to proliferate and morph into sensory cells.
Zheng-Yi Chen, HMS associate professor of otology and laryngology, Massachusetts Eye & Ear Infirmary
Jeffrey Hubbell, Merck Serono Chair in Drug Delivery, EPFL
New generation of auditory brainstem implants
The cochlear implant (CI), a device that bypasses the deaf inner ear to convey electrical signals directly to the auditory nerve, has been the most successful neural prosthesis over the past few decades, with over 200,000 in use worldwide. However, some patients cannot receive the CI due to an absent or damaged inner ear or auditory nerve. The auditory brainstem implant (ABI) in its current form bypasses the auditory nerve to directly stimulate the central auditory pathways found in the brain using a rigid electrode paddle. Unlike most CI users, the vast majority of ABI patients do not understand speech and many have side effects due to electrical current spread. An exciting new approach is the use of light, or optical stimulation, to provide more selective activation of auditory neurons. EPFL and HMS researchers will develop and test a new flexible array with electrical and optical electrodes to conform to the surface of the brain and stimulate the central auditory pathways in a more precise manner.This work will enhance the performance of existing ABI devices and provide the basis for a new generation ABI device.
Daniel J. Lee HMS assistant professor of otology and laryngology, Massachusetts Eye and Ear Infirmary
Christian Brown, HMS associate professor of otology and laryngology, Massachusetts Eye and Ear Infirmary
Stéphanie P. Lacour, professor in the Laboratory for Soft Bioelectronic Interfaces, EPFL
Philippe Renaud, professor at the Microsystem Laboratory, EPFL
Nicolas Grandjean, professor in the Laboratory of Advanced Semiconductors for Photonics and Electronics, EPFL
Walking again
A complete spinal cord injury leaves a person paralyzed with no hope of recovery, because the brain can no longer send signals to body’s extremities. EPFL has already made groundbreaking research in spinal cord stimulation using electrodes and pharmaceutics to reawaken the dormant circuitry that controls the legs, allowing animals to walk again, but involuntarily. For this locomotion to become voluntary, signals must come from the brain. HMS is working on silencing two genes that could lead to the re-growth of the neural fibers severed in the accident, bridging the injury and re-establishing voluntary leg movement when coupled with stimulation.
Zhigang He, HMS associate professor of neurology, Children’s Hospital BostonClifford Woolf, HMS/ Children’s Hospital Boston
Stéphanie P. Lacour (assistant professor of microtechnology) and Grégoire Courtine, associate professor of life sciences EPFL
The Wyss Institute for Biologically Inspired Engineering at Harvard University announced today that it has been awarded a $3.7 million contract (including option) from the Defense Advanced Research Projects Agency (DARPA) to develop a genetic security system that would track an organism’s history.
The proposed DNA-based memory device would sit inside a bacterium and create a permanent record of its historical experiences in much the same way as the “Track Changes” feature of word-processing software records successive edits in an electronic document. Such a bacterial background check would be analogous to biological forensic tools, such as fingerprint analysis, DNA testing and blood typing.
The DARPA project will be led by Wyss Institute core faculty member Pamela Silver, who is a professor of systems biology at Harvard Medical School and the first Director of Harvard’s Program in Systems Biology. Co-Principal Investigators will be James Collins, also a Wyss Institute core faculty member as well as professor of biomedical engineering at Boston University, and Jason Kelly, a founder and principal scientist at the Boston-based startup Ginkgo Bioworks.
The project team is charged with overseeing development of a bacterial memory system that actively reports on and tracks the history and status of an organism, providing information on its specific experiences, such as exposure to an antibiotic.
This type of tracking system could protect commodity biomanufacturing by tracking the theft of proprietary bacterial strains that have been metabolically engineered to produce high-value products, such as biofuels or chemicals. It could also enhance the security of bacteria that are being studied in laboratory settings and discourage the misuse of dangerous biological pathogens.
The device would need to be robust enough to function in the field, while also maintaining accurate historical records in the face of a wide range of environmental stresses, including the death of the bacterium that it is charged with tracking.
“This would be one of the first DNA-based memory systems to accurately track bacteria and it represents just the kind of challenging–and potentially game-changing—work that we do best here at the Wyss Institute,” said Wyss Institute Founding Director Donald Ingber. “We are happy to collaborate with DARPA in creating a new way to help ensure that bacterial strains created for science and industry are not misused in ways that could harm people or endanger our access to important products .”
