2017-2018 HMS Affiliates' Research

Each year, Harvard Medical School’s 15 internationally renowned affiliates care for thousands of patients using the latest medical knowledge and technologies while conducting research in basic, clinical and population sciences. Below is just a sample of some of the new insights and innovations emerging from HMS affiliate labs, clinics and educational endeavors during 2017-2018.

Beth Israel Deaconess Medical Center

Personalized cancer vaccine for an acute form of leukemia

In a clinical trial led by investigators at Beth Israel Deaconess Medical Center and reported in Science Translational Medicine, a personalized cancer vaccine markedly improved outcomes for patients suffering from acute myeloid leukemia (AML), a potentially lethal blood cancer. The vaccine, which emerged from a long-term collaboration between Beth Israel Deaconess and Dana-Farber Cancer Institute, stimulated powerful immune responses against AML cells and resulted in protection from relapse in a majority of patients. More than 70 percent of trial participants remained in remission at an average follow-up period of more than four years. After receiving a series of injections of the vaccine, patients demonstrated an increase in the number of leukemia-specific T cells in the blood and bone marrow. T cells are immune cells critical to the body’s ability to recognize and remember pathogens like viruses, or in this case, cancer cells. Present only in low numbers before vaccination, T cells recognizing AML cells were expanded after vaccination, potentially providing long-term protection against the leukemia. MORE

Boston Children's Hospital

Rainbow-hued blood stem cells shed new light on cancer and blood disorders

A new color-coding tool is enabling scientists to better track live blood stem cells over time, which is key to understanding how blood disorders and cancers such as leukemia arise, report researchers from Boston Children’s Hospital’s Stem Cell Program. In Nature Cell Biology, they describe the use of their tool inzebrafish to track the blood stem cells that the fish are born with, the clones (copies) that these cells make of themselves, and the types of specialized blood cells to which they give rise (red cells, white cells and platelets). Because zebrafish are surprisingly similar to humans genetically, the tool has many implications for hematology and cancer medicine. People are born with a certain number of blood stem cells and rely on them for life. Various blood disorders and cancers are thought to arise when a mutant clone of an original blood stem cell starts to dominate. To understand what actually happens with blood stem cells over time, the research team used a specially bred zebrafish that has multiple copies of genes for red-blue-gene fluorescent protein scattered through its genome. In their color-coded system, the researchers were able to mark each stem cell born with a different color and then follow the colors through development to see how many stem cells of each color were present in the adult fish. Other scientists have developed tracking systems based on genetic barcodes, but these require dissecting the cells, therefore they cannot analyze living, circulating cell populations. The Boston Children’s system is based on color, so the cells do not have to be destroyed to analyze their clonality. It provides a starting point for exploring, for example, why and how a particular blood stem cell clone may begin to expand as people age, posing a risk for leukemia, or how cancer chemotherapy can sometimes transform tumor cells.MORE

Brigham and Women’s Hospital

Ultra-long acting pill offers new hope in eliminating malaria

Investigators from Brigham and Women’s Hospital and their collaborators have developed a long-acting drug delivery capsule designed to reside in the stomach and release a daily dose of medicine for weeks at a time. To test the capsule’s real-world applications, the team used both mathematical modeling and animal models to investigate the effects of delivering a sustained therapeutic dose of a drug called ivermectin, which is used to treat parasitic infections such as river blindness and has an added bonus of helping to keep malaria-carrying mosquito populations at bay. In results published in Science Translational Medicine, the team found that in large animal models the capsule safely stayed in the stomach, slowly releasing the drug for up to 14 days, which potentially provides a new way to combat malaria and other infectious diseases. MORE

Cambridge Health Alliance

Residents trained to promote social change

To reduce health disparities and promote social change, Cambridge Health Alliance has transformed a popular elective into a required social medicine and research-based health advocacy course in the health system’s Internal Medicine Residency Program. Featured in Academic Medicine in 2017, this yearlong curriculum, which includes 100 hours of didactic and experiential study, teaches residents about health disparities, global health, U.S. health reform and human rights. Residents also participate in community organizing skills workshops, connect with inspiring role model advocates and meet with media professionals. A central component is the research-based health advocacy project, in which residents work as a group to identify a socioeconomic factor that has negatively influenced their patients' care and then develop a research study to investigate it. The projects have produced significant scholarship over the past five years, including a study on the impact of the Patient Protection and Affordable Care Act on Americans with chronic disease published in 2017 in the Annals of Internal Medicine that showed that, although ethnic minorities had improvements in some outcomes, approximately one in five blacks and one in three Hispanics with a chronic disease continued to lack coverage and access to care one year after implementation of the Affordable Care Act’s major coverage expansion in 2014. MORE

Cambridge Health Alliance

Scientists identify unique genomic features in testicular cancer

Providing the most detailed genomic information to date on testicular tumors, scientists at Dana-Farber Cancer Institute have identified unique genomic changes that may be integral to testicular cancer development and explain why the great majority are highly curable with chemotherapy, unlike most solid tumors. Cancers of the testes are known as germ cell tumors as germ cells produce sperm and eggs. Although rare, primary testicular germ cell tumors are the most common solid cancers in young men. Most of the tumors are highly sensitive to chemotherapy, and more than 90 percent of patients are cured, even when the cancer has metastasized. However, some tumors become chemotherapy-resistant, and as a result, about 10 percent of patients with metastatic germ cell tumors die. Previous studies of the genomes of testicular tumors have revealed mutations and chromosome damage but have not pinpointed specific alterations or events linked to chemosensitivity or resistance. In this new research reported in Nature, scientists conducted tests on testicular tumor samples using whole-exome DNA sequencing and RNAtranscriptome analysis, and then they correlated the findings with clinical outcomes data. They found a unique genomic signature that drives the tumors and discovered that the tumors’ sensitivity to chemotherapy results from the cancer cells being highly primed to self-destruct. These findings may shed light on factors in other cancers that influence their sensitivity to chemotherapy. MORE

Harvard Pilgrim Health Care Institute

Ventilator procedures and patient outcomes

The standards of care in ventilator bundles, a group of care guidelines for patients undergoing mechanical ventilation, are ubiquitous, but the absolute and relative value of each bundle component was unclear. As published in JAMA Internal Medicine in a retrospective study of 5,539 consecutive patients, researchers at Harvard Pilgrim Health Care Institute evaluated the associations between individual and collective ventilator bundle components and patient outcomes as measured by time to extubation, ventilator mortality, time to hospital discharge and hospital death. They found that head-of-bed elevation, sedative infusion interruptions, spontaneous breathing trials and thromboembolism prevention appeared to be beneficial. But daily oral care with the disinfectant chlorhexidine was associated with an increased risk for ventilator mortality, and procedures to prevent stress-induced ulcers were associated with an increased risk for ventilator-associated pneumonia. MORE

Hebrew SeniorLife

Tube-feeding drops dramatically in nursing home residents with dementia

Feeding tube insertion rates among nursing home residents with advanced dementia and eating dependency dropped approximately 50 percent between 2000 and 2014, according to a study published in JAMA. A research team led by the Hebrew SeniorLife’s Institute for Aging Research, with colleagues at Brown University and the University of Washington, reviewed data on more than 71,000 advanced dementia residents in nursing homes across the United States. They found the proportion of residents receiving feeding tubes declined from 11.7 percent in 2000 to 5.7 percent in 2014. Among white patients, insertion rates declined from 8.6 percent to 3.1 percent while rates in black patients declined from 37.6 percent to 17.5 percent—a 50 percent drop in both cohorts. This decline parallels the emergence of research and expert opinion that discourages tube feeding. In the future, to ensure that recommendations are disseminated and racial disparities are reduced, the researchers argue that fiscal and regulatory policies are needed that discourage tube feeding and promote a palliative approach to feeding problems in people with dementia.MORE

Joslin Diabetes Center

Signals from fat may aid diagnostics and treatments

Fat cells do more than send out hormones and other signaling proteins that affect many types of tissues. As published in Nature, scientists at Joslin Diabetes Center have identified a route by which fat can deliver a form of small RNAs called microRNAs that help regulate other organs. Focusing on microRNAs from fat cells released into the blood via tiny sacks called exosomes, they studied a mouse model genetically modified so its fat cells could not create microRNAs. In these mice, the total population of microRNAscirculating in exosomes dropped significantly. But this decrease could be restored when normal fat was transplanted into these mice, indicating many of the microRNAs in circulation were coming from fat. The scientists also studied people with two forms of lipodystrophy, a condition in which fat is lost or genetically not present. In both groups, the levels of microRNAs circulating in exosomes were lower than normal, which suggests the microRNAs generated by fat might aid in diagnostics for metabolic conditions such as obesity, type 2 diabetes and fatty liver disease. They also found that circulating microRNAs in exosomescan regulate gene expression in the liver and perhaps other tissues, which suggests the possibility that fat cells can be used to develop gene therapies that will aid in the treatment of metabolic diseases, cancer or other conditions of the liver or other organs. MORE

Judge Baker Children’s Center

Website for parents on adolescent depression

Distilling years of research, practice and advocacy into an interactive, web-based program to help individuals experiencing depression, as well as those living with or working with people experiencing depression, the Judge Baker Children’s Center has created two websites: Parent Talk, a resource for parents facing depression within the family, and Family Talk, a training course for clinicians helping these families. Parent Talk was created by researchers at Judge Baker Children’s Center, Boston Children’s and the Robert S. and Grace W. Stone Primary Prevention Initiatives grant program at the Wellesley Centers for Women, Wellesley College. It has been designed to enhance the lives of youth potentially experiencing depression and to help parents learn what depression is and how to maintain a positive influence on their child’s functioning, even if they are coping with depressive symptoms themselves. The Parent Talk website consists of four separate modules: Introduction to Parent Talk, Adolescent Depression, Adolescent Depression Prevention, and Parental and Adult Depression. The hope is that through this resource parents will learn what adolescent depression is and how to recognize depressive symptoms in their children, understand risk and resilience in teens, find out about treatment and prevention programs, identify effective steps that they can take as parents to strengthen family bonds, and discover available resources. MORE

Massachusetts Eye and Ear

Evidence of ‘hidden hearing loss’ in young adults


For the first time, researchers from Massachusetts Eye and Ear have linked symptoms of difficulty understanding speech in noisy environments with evidence of cochlear synaptopathy, a condition known as hidden hearing loss. As published in PLOS ONE, the investigators developed a series of tests to measure hidden hearing loss. Participants exposed to noise on a regular basis showed reduced responses from the auditory nerve, and that loss was matched with difficulty understanding speech in noisy and reverberating environments. However, hearing sensitivity and the ability to understand speech in quiet environments were the same across all subjects. Hearing loss typically arises from damage to the sensory cells of the inner ear (or cochlea), which convert sounds into electrical signals and/or the auditory nerve fibers that transmit those signals to the brain. It is traditionally diagnosed by elevation in the sound level required to hear a brief tone as revealed on an audiogram, the gold standard test of hearing sensitivity. But in hidden hearing loss, the connections between the auditory nerve fibers and the sensory cells are damaged, and this occurs well before the loss of the sensory cells themselves. Loss of these connections likely contributes to difficulties understanding speech in challenging listening environments and may be important in the generation of tinnitus (ringing in the ears) or hyperacusis (increased sensitivity to sound). MORE

Massachusetts General Hospital

Study suggests how ‘super-agers’ retain youthful memory

In a research program aimed at understanding how some older adults retain youthful thinking abilities and the brain circuits that support those abilities, a study at Massachusetts General Hospital showed that a remarkable group of older adults whose memory performance is equivalent to that of younger individuals have key areas of the brains that resemble those of young people. Most older adults experience a gradual decline in memory ability, but researchers also have described older adults, sometimes called super-agers, with unusually resilient memories. While previous research on super-aging has compared people over age 85 to those who are middle-aged, this study compared people around typical retirement age with young adults. Published in The Journal of Neuroscience, the study enrolled 40 adults ages 60 to 80, including 17 who performed as well as adults four to five decades younger on memory tests and 23 with normal results for their age group, and 41 young adults ages 18 to 35. Imaging studies revealed that the brains of super-agers were comparable in size to those of young adults, and in some cases, there was no difference in thickness. Critically, the research showed that super-agers not only had no shrinkage in key brain networks, but the size of these regions correlated with memory ability. Understanding which factors protect against memory decline could lead to important advances in preventing and treating age-related memory loss and possibly even various forms of dementia. MORE

McLean Hospital

Medical marijuana use may improve cognitive performance

Preliminary evidence from a McLean Hospital study suggests that medical marijuana may not impair—and may actually improve—executive functioning in adults. As published in Frontiers in Pharmacology, this research examined the impact of medical marijuana use on cognitive performance and related measures by monitoring a patient’s cognitive performance at baseline (before treatment) and after three, six, and 12 months of medical marijuana treatment. After three months, patients actually performed better on certain cognitive tasks, specifically those mediated by the frontal cortex. Study participants also reported improvements in their specific clinical conditions, sleep and overall health, as well as a decreased use of conventional medications, including a 42 percent reduction in opioid use. While a growing body of evidence suggests recreational marijuana use adversely affects brain function, critical questions regarding the impact of medical marijuana remain unanswered. Medical marijuana products are often low in tetrahydrocannabinol (THC), the primary psychoactive component of the plant and high in other cannabinoids, including cannabidiol (CBD), a nonpsychoactive component touted for its therapeutic potential. Recreational marijuana typically contains high THC levels and little to no CBD. This longitudinal study will continue for at least two years. MORE

Mount Auburn Hospital

Leadership training spans all hospital disciplines

To train leaders within all fields and at all levels of the hospital, Mount Auburn Hospital has created an Interprofessional Leadership Academy, a nine-month leadership course that unites clinicians and nonclinical staff in a training program designed to enhance each person’s leadership capabilities and success in their respective roles, while it imparts collaborative skills across all disciplines to enhance work efficiency and improve patient outcomes. Launched in 2015, this program is distinctive because other hospital leadership programs generally provide leadership training for clinical staff that is separate from nonclinical disciplines, rather than grouping people from all professions and levels together. Even though leaders across a spectrum of health care careers are charged with different day-to-day responsibilities, this program focuses on a core set of broadly relevant, common leadership skills with the belief that there is value in people in different health care careers learning how to approach shared management and leadership challenges together. In the first two years, a total of 28 hospital staff have completed the course, with doctors, nurses and pharmacists learning collaborative leadership skills alongside people in fields such as finance, information technology, chaplaincy and environmental services. The dynamics of the program’s first two years were presented to the Society of General Internal Medicine in April 2017 as exemplary of how collaborative leadership and teamwork is needed on all levels and between disciplines within a health care organization to be most effective.

Spaulding Rehabilitation Network

Shedding light on how humans walk aided by robots

In a study published in Science Robotics, researchers at Spaulding Rehabilitation Network measured how the gait of patients changed in response to forces applied by robotic machines fastened to their legs that gently prod them to walk. To the team’s surprise, the walkers adjusted their stride in response to a change in the length, but not the height, of their step, even when step height and length were disturbed at the same time. The scientists believe this discrepancy can be explained by the central nervous system’s primary reliance on stability when determining how to adjust to a disruption in normal walking: that is, lifting the foot higher mid-stride doesn’t really make patients that much less stable, but placing the foot closer or further away from their center of mass can throw off their balance so the body adjusts much more readily to that disturbance. However, this prioritization of stability means that other aspects of walking, like the height of the foot off the ground or the angle of the toes, may require treatment beyond walking with a typical rehabilitation robot. To modify step height, for example, would require robots designed in such a way that the change in height, which the brain normally interprets as neutral, becomes challenging to the patient’s balance. Most robots used in clinical settings today do not allow for that kind of customization. MORE

VA Boston Healthcare System

Universal immune mechanism helps regulate sleep

A study led by investigators at the VA Boston Healthcare System revealed that sleep may be regulated in part by several brain-based immune proteins collectively called NLRP3 inflammasome, which works by unleashing a cascade of immune molecules in response to inflammation and infection. Scientists have known for a while that certain immune molecules enhance sleep and are activated by infection, but this is the first study suggesting a common underlying mechanism that regulates sleep and plays a critical role in recuperative sleep responses. Published in Brain, Behavior and Immunity, the study in mice showed that the inflammasome recruits a sleep-inducing molecule to trigger somnolence following sleep deprivation and exposure to a bacterial toxin. Animals lacking genes for this protective immune complex showed profound sleep aberrations. These observations also suggest that the constellation of sleep-regulating proteins regulated by inflammasome may play a role in protecting the brain from the effects of sleep deprivation and infection. These findings may become the basis of therapies for people with chronic sleep disorders and sleep disturbances secondary to other diseases. MORE