2016-2017 HMS Affiliates' Research

For more than 200 years, Harvard Medical School affiliates have been key partners in the School’s education, research and patient care endeavors. Today, 15 affiliates house nearly 12,000 HMS faculty, who are seeking greater understanding of how cells work and designing clinical studies to transform medical care worldwide. Just a few of the remarkable discoveries made in 2016-2017 include the following:

Beth Israel Deaconess Medical Center

Vaccine protection against Zika virus

The rapid development of a safe and effective vaccine to prevent the spread of the Zika virus is a global priority as infection in pregnant women is shown to lead to fetal microcephaly and other major birth defects. As published in Nature, a team led by researchers at Beth Israel Deaconess Medical Center, in collaboration with scientists at Walter Reed Army Institute of Research and the University of São Paulo, demonstrated that two different Zika virus vaccine candidates provided complete protection in mice against a strain from Brazil, which suggests that a Zika vaccine for humans may be feasible.

Boston Children’s Hospital

Gene therapy has potential to help restore hearing

With more than 70 different gene mutations known to cause deafness, scientists at Boston Children’s Hospital envision a day when patients’ hearing is restored by gene therapy. In studies of mice published in Science Translational Medicine, the researchers focused on deafness caused by a mutation of a gene called TMC1, which accounts for 4 to 8 percent of deafness and encodes for a protein that helps convert sound into signals that travel to the brain. When a functioning TMC1 gene was delivered into the ears of deaf mice via an engineered adenovirus, the sensory hair cells began responding to sound and the mice began to hear. Ultimately, the team hopes to start clinical trials using gene therapy to prospectively restore hearing in humans.

Brigham and Women’s Hospital

Changes in gut bacteria of patients with multiple sclerosis

A connection between the bacteria living in the gut and immunological disorders such as multiple sclerosis has long been suspected, and for the first time, researchers detected clear evidence of changes that connect the two. Investigators from Brigham and Women’s Hospital found that people with multiple sclerosis have different patterns of gut microorganisms than people without the disease. In addition, patients receiving treatment for MS have different patterns than untreated patients. This new research supports recent studies linking immunological disorders to the gut microbiome and may have implications for the development of new therapies.

Cambridge Health Alliance

Collaborative program reduces juvenile arrests

To reduce juvenile arrests, Cambridge Health Alliance partnered with police, schools and human services departments in Cambridge, Mass., in a citywide initiative called the Cambridge Safety Net Collaborative. As published in the American Psychological Association’s journal Psychological Services, Cambridge Health Alliance psychologists who helped establish this multiagency program reported on how community partners are working together to identify and determine the best interventions for at-risk youth, such as mentoring opportunities, after-school programs or mental health action. Police officers trained to handle youth diversion strategies work with the psychologists who provide training, consultation and access to formal mental health services. Since the program’s inception in 2007, juvenile crime arrests have dropped by more than 50 percent. Read a description of a collaborative community approach to impacting juvenile arrests.

Dana-Farber Cancer Institute

Blood test detects genetic mutations in lung cancer

A “liquid biopsy,” or simple blood test, can rapidly and accurately detect mutations in two key genes in non-small cell lung tumors, the most common form of lung cancer. As reported in JAMA Oncology, researchers at Dana-Farber Cancer Institute and other institutions demonstrated the test’s potential as a clinical tool for identifying patients who can benefit from drugs that target those mutations. Technically known as rapid plasma genotyping, the test involves analyzing blood that contains free-floating DNA from cancer cells for mutations or other abnormalities. This noninvasive method of screening a cancer for common genetic fingerprints avoids the challenges of traditional invasive biopsies.

Harvard Pilgrim Health Care Institute

Opioid prescribing after nonfatal overdose

Among patients receiving long-term opioid prescriptions for chronic pain who experience a nonfatal overdose event, 91 percent continue to receive prescriptions for opioids. But opioid discontinuation after overdose is associated with lower risk of repeat overdose. As published in the Annals of Internal Medicine, researchers at Harvard Pilgrim Health Care Institute hypothesized these findings are a consequence of a fragmented health care delivery system in which providers prescribing opioids for pain may be unaware of a prior overdose event. Making information available about these readily identifiable events from claims data may represent an opportunity to intervene and improve subsequent outcomes. Read Opioid Prescribing After Nonfatal Overdose and Association With Repeated Overdose: A Cohort Study

Hebrew SeniorLife Institute for Aging Research

Reduction of dual-task costs in healthy elders

Dual-tasking, especially walking or standing while performing a separate cognitive task, disrupts performance in one or both tasks, and this problem often increases with aging. As dual-tasking activates a network of brain regions including the prefrontal cortex, a multi-institutional team led by the Hebrew SeniorLife Institute for Aging Research investigated whether transcranial direct current stimulation (tDCS) would enhance dual-tasking in older adults. In a paper published in the Journal of Cognitive Neuroscience, healthy older adults were assessed before and after 20 minutes of tDCS designed to increase the excitability of the left prefrontal cortex. Findings showed that this stimulation, as compared to sham (i.e., placebo) stimulation, reduced the "cost" of dual-tasking on walking performance. These results indicate that a decline in dual-task capacity may not necessarily be an obligatory consequence of aging. Moreover, noninvasive brain stimulation may serve as a novel approach to preserving the capacity to dual-task into senescence. Read Reduction of Dual-task Costs by Noninvasive Modulation of Prefrontal Activity in Healthy Elders

Joslin Diabetes Center

New approach may aid wound healing in diabetes

In people with diabetes, a small skin wound can become a big problem because wounds don’t heal as well as they do in people without the disease. Impaired healing is a particular concern in chronic diabetic foot ulcers, which leads to more than 80,000 lower limb amputations each year in the U.S., because treatments for chronic wounds largely do not work in diabetic patients. As published in the Journal of Clinical Investigation, research at Joslin Diabetes Center suggests a potentially more effective therapy using connective-tissue cells, called fibroblasts, gathered from human skin samples. The treatment would use a patient’s own cells, modified to lower production of a protein called protein kinase C delta, which the scientists implicated in the slow formation of blood vessel cells in diabetic wounds.

Judge Baker Children’s Center

Quality Care Initiative: A strategic collaboration with Massachusetts

The Quality Care Initiative at Judge Baker Children’s Center helps children and families by translating evidence-based strategies into sustainable practice changes in real-world settings. A recent example involved a collaboration with the Massachusetts Department of Public Health to conduct a comprehensive implementation assessment of an in-home intervention for maternal depression. It assessed current strengths and barriers to statewide implementation, provided recommendations for improvements within current implementing agencies, identified strategies for sustainability, and informed potential future expansion of the program. This assessment and consultation approach was presented at the Institute for Healthcare Improvement’s Scientific Symposium and the Harvard Psychiatry Research Day Poster Session. Read about Quality Care Initiative

Massachusetts Eye and Ear

Genetic associations that influence glaucoma

Researchers from Massachusetts Eye and Ear were among leaders of an international effort to identify three genetic associations that influence susceptibility to primary open-angle glaucoma, the most common form of adult-onset glaucoma and the leading cause of irreversible blindness in the world. In the largest genome-wide association study for primary open-angle glaucoma, investigators studied more than 4,000 cases and 30,000 controls using human genomes collected through the NEIGHBORHOOD consortium, a National Eye Institute collaborative. The researchers identified relationships between primary open-angle glaucoma and three genetic foci: TXNRD2, ATXN2 and FOXC1. The findings, published in Nature Genetics, provide insights that may ultimately be used to develop gene-based testing and treatment strategies for glaucoma.

Massachusetts General Hospital

Human amyloid-beta acts as natural antibiotic

A Massachusetts General Hospital study provides additional evidence that amyloid-beta protein, which is deposited in the form of beta-amyloid plaques in the brains of patients with Alzheimer’s disease, is a normal part of the innate immune system, the body’s first-line defense against infection. Published in Science Translational Medicine, the study showed that expression of human amyloid-beta was protective against potentially lethal infections in mice, roundworms and cultured human brain cells. The findings indicate that Alzheimer's-associated amyloid plaques may be part of a natural process for trapping microbes and suggest there may be limitations to therapies designed to eliminate amyloid plaques from patients’ brains. This research also may lead to potential new therapeutic strategies.

McLean Hospital

Abnormalities in circadian rhythms linked to neurochemical changes

Results of a first-of-its-kind study have linked abnormalities in circadian rhythms to changes in specific neurotransmitters in the brains of people with bipolar disorder. As published in Biological Psychiatry, a McLean Hospital study points to specific neuroanatomical changes in human subjects with these illnesses, particularly to neurons that regulate anxiety and stress response. For decades, evidence has suggested something is wrong with circadian rhythms in people with bipolar disorder, but there has been a huge gap in understanding how altered circadian rhythms contribute to their symptoms. Growing evidence points to a key role for the neurotransmitter somatostatin in schizophrenia and bipolar disorder. In the amygdala, a part of the brain involved in anxiety and stress, somatostatin plays an important role in the regulation of anxiety and depression, often co-occurring in these disorders. Studies are now underway to characterize the protein signals involved and how their rhythm of expression changes, potentially leading to new light-based therapies for bipolar disorders.

Mount Auburn Hospital

Spread of Zika virus in the Western Hemisphere requires increased vigilance

As published in the Annals of Internal Medicine, physicians at Mount Auburn Hospital described the worldwide spread of the Zika virus, a mosquito-borne flavivirus, with infection reported by January 2016 in 20 countries and territories in the Americas. For patients returning from countries with known outbreaks or possible circulation of the virus, clinicians need to watch for symptoms, such as a rash, arthralgias and conjunctivitis, that typically develop within a week of being bitten by a Zika-infected mosquito. Zika infection can be confirmed by polymerase chain reaction (PCR) testing during acute illness or serologic testing, with the latter currently performed only at the Centers for Disease Control and Prevention or at state health departments, but it also must be differentiated from other possible diseases or co-infections such as dengue and chikungunya. Patients who are world travelers should be advised to use antivector measures, and pregnant women should avoid outbreak areas due to the risk of microcephaly in the developing fetus.

Spaulding Rehabilitation Network

Factors in reporting concussion-like symptoms in high school athletes

Safely returning athletes to sport after concussion relies on accurately determining when their symptoms resolve and being able to differentiate between concussions and concussion-like symptoms. In a study of 31,958 high school athletes published in JAMA Pediatrics, researchers at Spaulding Rehabilitation Network evaluated the reporting of concussion-like symptoms, looking for predictors of reporting in uninjured athletes. They found that girls were more likely to report concussion-like symptoms than boys and preexisting conditions, such as a history of migraines, psychiatric condition, substance abuse, or attention-deficit/hyperactivity disorder, also were predictors of reporting concussion-like symptoms. The weakest independent predictor of reporting for both sexes was history of prior concussions. Read Factors Associated With Concussion-like Symptom Reporting in High School Athletes

VA Boston Healthcare System

Precision oncology program launched

The VA Boston Healthcare System implemented the Precision Oncology Program, a clinical care program with a research component intended to bring precision medicine and cutting-edge cancer diagnostics and treatment to veterans through targeted genetic testing and analysis. Launched by a team of hematologists and oncologists, the goal of the program is to maximize agility and potential within the VA Healthcare System, to improve the standard of care through research, to find effective treatments and cures for cancer, and to customize medical decision-making for individual patients with cancer. Developed and piloted in Veterans Integrated Service Network 1, which included VA Boston, the program is now available to all VA Medical Centers nationally. Read about the VA Precision Oncology Program