Study Identifies New Targets for Huntington’s Disease Research

Ghazaleh Sadri-Vakili, PhD, is the director of the NeuroEpigenetics Laboratory at Massachusetts General Hospital’s Institute for Neurodegenerative Diseases (MIND).  Her work investigating the genetics of Huntington’s disease was recently featured in an article on the Mass General Giving website.

Here are five things to know:

  1. Huntington’s disease (HD) is a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain. Symptoms typically start occurring between the ages of 30 and 50. The disease is highly heritable—each child of a parent with HD has a 50% chance of inheriting the faulty gene.
  2. According to the Huntington’s Disease Society of America (HDSA), symptoms of HD typically begin with a loss of coordination and cognitive skills. These declines get more pronounced as the disease progresses. In late stages, HD patients lose the ability to walk and speak, and choking becomes a major concern. Death is typically due to complications from the disease and not the disease itself.
  3. Researchers at Massachusetts General Hospital have been at the forefront of research into the genetic underpinnings of Huntington’s disease for the past two decades. In 1983, a team led by James Gusella, PhD, identified the section on chromosome 4 where the HD gene was located. In 1993, a multi-institutional research group that included Marcy E. MacDonald, PhD, and Dr. Gusella identified the gene itself.
  4. Recently, a research team led by Ghazaleh Sadri-Vakili, PhD, has been studying how gene expression differs in patients with HD. Her team has identified two ways in which a genetic pathway known as the Hippo pathway malfunctions in HD. These malfunctions cause HD patients to produce too much of an enzyme called MST, and not enough of a protein called YAP.
  5. If researchers are able to identify drugs that correct this imbalance, they may be able to develop treatments that slow or halt the progression of the disease.

Weekend Links

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We’ve hand-picked a mix of Massachusetts General Hospital and other research-related news and stories for your weekend reading enjoyment:

Creative Minds: A New Way to Look at Cancer

Better Patient-Provider Communication Needed for Obesity Care

Eugenics 2.0: We’re at the Dawn of Choosing Embryos by Health, Height, and More

6 Speaking Tips for Scientists and Engineers (editor’s note: Melissa Marshall, featured in this article, recently spoke to Mass General clinicians about how to effectively present scientific work. We were so impressed by her talk that we wanted to introduce her to our readers) 

Looking for a great book for the young scientist in your life? The long list of 2018 AAAS/Subaru SB&F (Science Books and Films) Prize winners for Excellence in Science Books has been released. Prizes are awarded each year in the following categories:

  • Children’s Science Picture Books
  • Middle Grade Science Books
  • Young Adult Science Books
  • Hands on Science Books

See the full list here

 

Top photo: courtesy of Tim Lahan, MIT Technology Review

Kamryn Eddy Finds Hope for Patients with Eating Disorders

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The people we encounter early in life can often have a profound impact on our future. For Massachusetts General Hospital psychologist Dr. Kamryn Eddy, a childhood friend influenced her career trajectory.

“I had a close friend in high school who had anorexia,” says Dr. Eddy. “As a result, she had a number of health concerns, including osteoporosis, and was told at age 16 that she would never be able to have children.”

She recalls being shocked that a doctor would give such a definitive and dire prognosis to someone so young. Eddy has kept in touch with her friend, who found help for her eating disorder and was eventually able to recover. Her friend now has a healthy young daughter.

“That early experience was one of my introductions to the world of eating disorders,” says Eddy. “Seeing my friend’s battle and eventual recovery from her illness also showed me that there can be hope for people suffering from eating disorders.” Continue reading “Kamryn Eddy Finds Hope for Patients with Eating Disorders”

How a 3D Model of Alzheimer’s Disease is Providing New Hope in the Search for Treatments

Reigning in Alzheimer’s disease continues to be a challenge — more than 10 million families are affected by this degenerative neurological disease, and the number of patients dying from the disease has increased 68 percent since 2010.

In the past decade, attempts at developing drugs to slow or halt the progression of Alzheimer’s disease have been unsuccessful. The traditional path for early testing of promising therapies – mouse models – has been ineffective, and more than a dozen major clinical trials have failed.

But scientists and clinicians at Massachusetts General Hospital’s Institute for Neurodegenerative Disease (MIND) have developed an innovative new approach that could significantly improve the drug development process.  The laboratory teams of Doo Yeon Kim, PhD, an investigator in the Genetics and Aging Research Unit at MIND, and Rudy Tanzi, PhD, have found a way to grow human neural stem cells in a three-dimensional gel matrix.

This gel system allows the neural cells to grow more naturally and form into 3-D networks just like they do in the brain. It also provides a more accurate model of the signature plaques and tangles that develop around these neurons in Alzheimer’s disease.

The stem cells used in this lab model are genetically engineered to produce two proteins that are the hallmarks of Alzheimer’s disease – β-amyloid and tau. In the brains of people with Alzheimer’s, excessive accumulation of β-amyloid results in the formation of plaques in the spaces between neural cells, while tau is the main component of destructive neurofibrillary tangles within the cells.

Until Dr. Kim’s success, no single model of Alzheimer’s disease contained both amyloid plaques and neurofibrillary tangles. It usually takes a year to develop plaques in mouse models, it took only six weeks to develop both plaques and tangles in the “dish.”

Dr. Kim is now working with a consortium of labs to test thousands of FDA-approved drugs in this “Alzheimer’s in a dish” model to see if any of the drugs are effective in reducing levels of p-tau, a protein that is increased in Alzheimer’s patients.

Of the 2,400 drugs that have been tested, the team had approximately 40 promising hits that they can now investigate further.

Learn more: https://giving.massgeneral.org/fresh-alzheimers-approach-sparks-hope/

Four Massachusetts General Hospital Researchers Receive Prestigious NIH Director’s Awards

Please join us in congratulating the four Mass General investigators who recently received director’s awards from the National Institutes of Health (NIH)! These awards are given to exceptionally creative scientists who propose innovative approaches with high-impact potential to major challenges in biomedical research.

Continue reading to learn more about each researcher and their proposed work as well as their reaction to receiving this award.

New Innovator Award

The New Innovator Award supports exceptionally creative early career investigators who propose innovative, high-impact projects.

Evan Macosko, M.D., Ph.D.
Broad Institute of MIT and Harvard, Massachusetts General Hospital

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“I am delighted and honored that the NIH is willing to support this high-risk technology project.  The lab can’t wait to get started on some potentially very impactful scientific work.”

Project Title: Slide-Seq: High-Resolution In Situ Expression Profiling for Neuropathology
Grant ID: DP2-AG-058488

Evan Macosko is a principal investigator in the Stanley Center for Psychiatric Research at the Broad institute, and an Assistant Professor of Psychiatry at Harvard Medical School. His research focuses on developing and leveraging new technologies in genomics to characterize pathophysiological mechanisms in neuropsychiatric diseases. As a postdoc in Steven McCarroll’s lab at Harvard Medical School, he developed a new method, Drop-seq, for performing highly parallel gene expression analysis of single cells from complex neural tissues. He completed a psychiatry residency at MGH and McLean Hospital, and is currently an attending psychiatrist at MGH. He holds a Ph.D. in Neuroscience and Genetics from Rockefeller University, and an M.D. from Weill Cornell Medical College.

Radhika Subramanian, Ph.D.
Massachusetts General Hospital and Harvard Medical School

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“I am extremely grateful and honored to receive the NIH Director’s New Innovator Award. The support provided by this award will allow my lab to pursue a new research direction where we will develop a versatile cell-free imaging platform that will enable us to decipher how spatial cues are encoded and decoded within cells. We expect that the toolkit established here will be applicable for elucidating the fundamental mechanisms that govern the spatial organization of cellular reactions that underlie diverse cell-­biological  processes of biomedical significance such as cell division, migration, and development.”

Project Title: A Versatile Platform for Reconstructing the Spatial Organization of Intracellular Signaling During Cell-Division
Grant ID: DP2-GM-126894

Radhika Subramanian is an Assistant Professor in the Department of Molecular Biology at Massachusetts General Hospital and the Department of Genetics at Harvard Medical School. Her lab focuses on elucidating the fundamental principles by which intracellular spatial organization on the micron-length scale is achieved by the collective activity of nanometer-sized proteins. Radhika received her M.Sc. in Chemistry from the Indian Institute of Technology in Delhi, India. She performed her doctoral research with Dr. Jeff Gelles at Brandeis University followed by postdoctoral training in the laboratory of Dr. Tarun Kapoor at the Rockefeller University. In addition to the NIH New Innovator Award, Radhika is a Pew Biomedical Scholar and a recipient of the Smith Family Award for Excellence in Biomedical Research.

Brian Wainger, M.D., Ph.D.
Massachusetts General Hospital | Harvard Medical School

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“I’m thrilled to receive the award. It’s a great honor, and I’m grateful for the hard work of my group, particularly Joao Pereira and Anna-Claire Devlin, that enabled it. It’s also of course due to very strong support from MGH, the departments of Neurology and Anesthesia, Critical Care & Pain Medicine. And with the award comes an even greater responsibility to produce research that ultimately helps our patients – I’m excited and humbled by that.”

Project Title: A Human Stem Cell-Derived Neuromuscular Junction Model for Amyotrophic Lateral Sclerosis
Grant ID: DP2-NS-106664

Brian Wainger is a physician scientist at Massachusetts General Hospital and Assistant Professor of Neurology and Anesthesiology at Harvard Medical School. He received his undergraduate degree in molecular biology from Princeton University and M.D./Ph.D. degrees from Columbia University, where he worked on ion channel physiology with Steven Siegelbaum. Following medical residency in the Partners Neurology Program and clinical fellowship in Interventional Pain Medicine at Massachusetts General Hospital, he completed a research fellowship with Clifford Woolf at Boston Children’s Hospital and the Masters Program in Clinical and Translational Investigation at Harvard Medical School. He is a Principal Investigator at Massachusetts General Hospital, Principal Faculty at the Harvard Stem Cell Institute and a member of the Harvard Neurobiology Program. His lab research focuses on modeling motor and sensory neuron diseases using stem cell technology and electrophysiology.

Early Independence Award

The Early Independence Award supports outstanding junior scientists with the intellect, scientific creativity, drive, and maturity to flourish independently by bypassing the traditional post-doctoral training period.

Zirui Song, M.D., Ph.D.
Harvard Medical School and Massachusetts General Hospital

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“It is an honor to receive this grant and join an inspiring community of investigators. I am grateful to the faculty and colleagues who made my training possible. This grant will allow me to continue my research on strategies to improve the value of care, including studying efforts to decrease costs, improve quality, and increase the sustainability of our public programs like Medicare. In addition, this grant provides an opportunity to better understand how providers are leading delivery system reforms on the front lines and how different segments of the population are faring in the era of health care reform.”

Project Title: Inequities in Health Outcomes in the Twenty-First Century: Understanding New Causes and the Impact of Delivery System Reforms on Health Care Disparities
Grant ID: DP5-OD-024564
Funded by the National Center for Complementary and Integrative Health

Zirui Song is an assistant professor of health care policy at Harvard Medical School and an internal medicine physician at Massachusetts General Hospital. His research has focused on health care spending and quality under new payment models for provider organizations, the impact of changes in Medicare physician payment policy, and the economics of health insurance in the Medicare Advantage program. He received a B.A. in Public Health Studies with honors from Johns Hopkins University, an M.D. magna cum laude from Harvard Medical School, and a Ph.D. in Health Policy, Economics track, from Harvard University, where he was a fellow in Aging and Health Economics at the National Bureau of Economic Research. He completed his residency training at Massachusetts General Hospital.

Brain Imaging Studies Provide New Insights into Biological Basis of Behaviors in Schizophrenia and Autism

Researchers at Massachusetts General Hospital are using brain imaging technology to learn more about how individuals with autism and schizophrenia view the world through different lenses.

Imagine sitting alone in an empty movie theater. Just before the film starts, another person comes in and takes the seat right next to you, even though there are plenty of other seats available.

How would you react?

Presumably, you wouldn’t be very comfortable. It would probably be difficult to concentrate on the movie. Your fight or flight response might even kick in.

How would your reaction differ if you were in a crowded theater, and the same person took the seat next to you because it was the only one left? In that context, it seems much more reasonable.

We have similar unspoken rules about making eye contact. Too much eye contact can seem threatening or flirtatious, while too little can make the other person think you are bored or disinterested.

Most of us manage these behaviors by instinct. But what happens when the brain circuitry driving them misfires? When the simple act of making brief eye contact causes the same burning sensation as if someone is staring right at you, or when your personal space bubble becomes so enlarged that others can make you uncomfortable without realizing it?

Two researchers at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital are using brain imaging technology to gain new insights into how the brain systems that typically manage personal space and eye contact work differently in individuals with schizophrenia and autism.

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Nouchine Hadjikhani, MD, PhD, and Daphne Holt, MD, PhD

Daphne Holt, MD, PhD, is exploring how perceptions of personal space differ in individuals with schizophrenia, and how these differences contribute to symptoms such as isolation and withdrawal. Nouchine Hadjikhani, MD, PhD, is studying how individuals with autism respond to eye contact, and how this can influence their behavior and social interactions. 

Their findings could revolutionize the way we understand, treat and assess those who suffer from these disorders. Continue reading “Brain Imaging Studies Provide New Insights into Biological Basis of Behaviors in Schizophrenia and Autism”

Lady Gaga’s Diagnosis Helps Shed Light on a Perplexing Chronic Pain Disorder

Despite her celebrity status, Lady Gaga has been remarkably honest and open about her struggles with fibromyalgia, a chronic pain disorder. The star announced her diagnosis on social media earlier this month, and just recently canceled tour dates due to disorder-related complications.

Fibromyalgia has traditionally been a challenge to diagnose and treat, because there is no test for it. Doctors make the diagnosis based on patient reported symptoms. Researchers at Mass General are hoping to change that by using imaging techniques to demonstrate brain changes in fibromyalgia patients and investigating potential causes for the disease.

What is fibromyalgia and what are the symptoms?

Fibromyalgia is a common chronic pain disorder that can be extremely debilitating. The disorder is characterized by widespread pain, accompanied with un-refreshing sleep, fatigue, memory and cognitive problems, sensitivity to temperatures, light, and sound, and headaches. It can also co-exist with other conditions including depression, anxiety and irritable bowel syndrome.

These symptoms severely impact the 5-10 million Americans living with this disorder. The pain and fatigue of fibromyalgia can make it difficult to maintain work and social obligations. Symptoms also come in waves at seemingly random intervals, which can blindside individuals.

What causes fibromyalgia?

It’s thought that disturbances in the central nervous system affect the way the brain processes pain signals, which amplifies the painful sensations that fibromyalgia patients experience. But why these disturbances occur remains a mystery.

Experts suggest that the disorder could be driven by several factors, including physical or emotional trauma, prior illness or infection, and genetics. Women are also more likely to develop fibromyalgia than are men, though researchers don’t know why.

In an effort to find answers to these questions, Marco Loggia, PhD, Associate Director of the Center for Integrative Pain NeuroImaging and a researcher in the Martinos Center for Biomedical Imaging at Massachusetts General Hospital, studies the brain mechanisms of pain in patients with fibromyalgia. His research suggests that some degree of brain inflammation may be at play, given that brain inflammation is common among chronic back pain sufferers and most fibromyalgia patients suffer from chronic back pain.

How is it treated?

There is no cure for fibromyalgia. As a result, the focus of treatment is on managing pain and improving quality of life for patients. However, patients often struggle to find the right combination of treatments to manage their condition.

Clinicians often recommend medications including pain relievers, anti-depressants, and anti-seizure drugs to reduce pain and improve sleep. Some patients also utilize therapies such as physical therapy or counseling and alternative treatments like massage therapy, yoga or acupuncture.

Is there stigma associated with fibromyalgia?

Because there are no lab tests to diagnose fibromyalgia, patients are frequently met with skepticism, even by their own primary care team. The pain they report is often dismissed as being “all in their head.”

In a recent interview with HealthDay News, Loggia said, “Many studies—and particularly those using brain imaging techniques such as functional magnetic resonance imaging—have now provided substantial support to the notion that the excessive sensitivity to pain that these patients demonstrate is genuine. I think that it is time to stop dismissing these patients.”

With celebrities like Lady Gaga raising awareness of this disease and researchers like Loggia investigating its causes and progression, could individuals suffering from fibromyalgia soon see advances in treatment and care—as well as more public understanding of this debilitating disorder?

To read more on this topic:

Research Awards and Honors: September 2017

Massachusetts General Hospital’s talented and dedicated researchers are working to push the boundaries of science and medicine every day. In this series we highlight a few individuals who have recently received awards or honors for their achievements:

Aguirre

Aaron Aguirre, MD, PhD, of the Cardiology Division and the Center for Systems Biology, has received a 2017 Physician/Scientist Development Award for “Morphology and Dynamic Functions of Pericytes in the Heart.” Aguirre’s project will use state-of-the-art microscopy techniques to better understand the role of pericytes—unique cells that line the outer walls of the smallest blood vessels in the heart. Funding for the Physician/Scientist Development Awards is provided by the Executive Committee on Research along with the Center for Diversity and Inclusion.

“I am grateful for the research support provided by the MGH Physician Scientist Development Award. It will allow me to expand my current research into a new direction and to generate critical preliminary data necessary for future grant applications.”

 

Chung

David Chung, MD, PhD, attending neurointensivist in the Neurology Department, has been awarded the Timothy P. Susco Chair of Research and the Andrew David Heitman Foundation Chair of Research from The Brain Aneurysm Foundation for his work, “Impact of Spreading Depolarizations and Subarachnoid Hemorrhage on Brain Connectivity.” He is one of 14 awardees, given to those whose work is impacting a disease that affects one in 50 people in the United States, often leading to death or lifelong disability.

My immediate reaction to receiving this award was gratitude towards my mentors in the Department of Neurology at MGH: Cenk Ayata, Jonathan Rosand, Guy Rordorf, and Leigh Hochberg. Without their support, this work would not be possible. A major question in Neurocritical Care is how to prevent poor outcome after a ruptured brain aneurysm. Even when we successfully repair the aneurysm, many patients will develop a syndrome of progressive brain damage for unknown reasons. This award will enable us to examine unexplored causes of brain damage and poor outcome with the goal of improving quality of life in survivors of the disease.”

 

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Julie Levison, MD, MPhil, MPH, of the Division of General Internal Medicine, has received a CFAR ADELANTE Award from the National Institutes of Health, the Office of AIDS Research and the NIH-funded Centers for AIDS Research to support new  investigators working on HIV research in Latinos. Hispanic/Latino populations in the U.S. currently bear a disproportionate burden of the HIV/AIDS epidemic. The ADELANTE team is composed of Dr. Levison (principle investigator), Dr. Margarita Alegría, chief MGH Disparities Research Unit, and Carmen Rios, Respite Case Manager at the Barbara McGinnis House.

“The ADELANTE award is a special type of research award because it recognizes the value of community-academic collaborations in overcoming disparities in HIV outcomes in Latino populations. In this study, we will use qualitative research to solicit the needs and priorities of HIV-infected Latino migrants with substance use disorders or who report male-to-male sex and we will use that feedback to tailor and evaluate a community-based intervention we have developed for HIV-infected Latinos with inconsistent HIV primary care attendance.”

 

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Fatima Cody Stanford, MD, MPH, MPA, adult and pediatric obesity medicine physician of the MGH Weight Center, Department of Medicine-Gastroenterology and Department of Pediatrics-Endocrinology, has received a 2017 Physician-Scientist Development Award from the MGH Center for Diversity and Inclusion for “Exploring Referral Patterns and Shared Decision Making Regarding Weight Loss Surgery in Adolescents and Young Adults with Moderate to Severe Obesity.” Funding for the Physician/Scientist Development Awards is provided by the Executive Committee on Research in conjunction with the Center for Diversity and Inclusion. Stanford also has been selected to the inaugural class of Emory University Alumni Association’s “40 Under Forty,” a selected group of outstanding young alumni with impressive track records who are “go-to” leaders.

“I am delighted to be the recipient of the MGH Physician Scientist Development award in partnership with the MGH Center for Diversity and Inclusion and ECOR. I believe that we are just at the beginning of discerning issues associated with addressing obesity in the pediatric and adult populations. This award allows me to ascertain information about shared decision making in adolescents and young adults with moderate to severe obesity in which weight loss surgery might be utilized to help them achieve a healthy weight. To our knowledge, no one has investigated the use of shared decision making regarding weight loss surgery in young people. This awards allows us to do just that.”

 

Temel GreerJennifer Temel, MD, director of the Cancer Outcomes Research Program and Hostetter MGH Research Scholar, along with Joseph Greer, PhD, program director of the Center for Psychiatric Oncology & Behavioral Sciences, have received a research funding award from the Patient-Centered Outcomes Research Institute (PCORI) for their research “Comparative Effectiveness of Early Integrated Telehealth Versus In-Person Palliative Care for Patients with Advanced Lung Cancer.” The new awards were given to those whose work specifically focuses on community-based palliative care delivery. The goal of this project is to determine if telehealth is an effective, patient-centered, and accessible delivery modality for early palliative care.

“We are overjoyed to receive this research award from PCORI. By testing novel models of care using telemedicine, we hope to demonstrate that greater numbers of patients with advanced cancer and their families can access and benefit from essential palliative care services closer to the time of diagnosis.”

 

Whetstine.jpgJohnathan Whetstine, PhD, of the MGH Cancer Center and Tepper Family MGH Research Scholar, has received a Lung Cancer Discovery Award from the American Lung Association. This award supports investigators at any level of research experience focusing on novel treatments or a cure for lung cancer. His goal is to use studies about histone modifiers to provide insights into tumor heterogeneity and emerging drug resistance so that better molecular diagnostics, epigenetic therapeutic molecules, or use of novel therapeutic combinations can be achieved in cancer treatment.

“We are very excited to receive this award from the ALA.  This support allows my group to continue to expand our lung cancer research program in the area of tumor heterogeneity and drug resistance. Most importantly, these resources allow us the opportunity to explore novel regulatory pathways driving heterogeneity and copy gains of regions affiliated with resistant lung cancer, which provides insights into novel diagnostics and therapeutic opportunities in this hard-to-treat cancer.”

 

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Alik Widge, MD, PhD, director of the Translational NeuroEngineering Laboratory, Division of Neurotherapeutics, has received the 2017 One Mind/Janssen Rising Star Translational Research Award from the One Mind Institute and Janssen Research & Development, LLC. This award identifies and funds pivotal, innovative research on the causes of and cures for brain disorders. Toward boosting the recovery of patients with illnesses such as schizophrenia, major depression or obsessive-compulsive disorder, Widge proposes to identify precisely the brain circuits that govern the inflexibility of thinking common among patients with such illnesses, and to test whether neurostimulation of these circuits could improve mental flexibility.

“I was very excited about the Rising Star award, for two reasons. First, it brings much-needed seed funding to our lab for an unconventional but possibly high-yield project. We have found that electrical brain stimulation in humans can improve mental flexibility — the ability to “take the road less traveled by” and explore new behavior strategies. That ability is impaired in many mental illnesses. Our problem is that we don’t yet know how the electrical stimulation improves flexibility. The Rising Star award will let us set up animal experiments to identify the circuit basis of the effect, findings we could then translate back into humans. 

Second, this is a really important award in psychiatric research. It’s brought our lab’s other work into the spotlight, which will help those projects progress. I’m grateful both to the OneMind Institute for the award and to the MGH team that helped me get the preliminary data that made it possible.”

Researchers and Clinicians Revolutionize Prevention Efforts for Brain Disease

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What if you had a strong family history of Alzheimer’s disease, but weren’t currently showing any symptoms? What could you do to stave off the cognitive decline and loss of memory associated with this devastating disease? A team of researchers and clinicians at Massachusetts General Hospital wants to be your resource in situations like these.

The Institute for Brain Health at Mass General is revolutionizing the way we treat brain disease by developing new strategies for prevention, risk reduction and early treatment. They work with individuals who are at high genetic risk for brain diseases as well as healthy individuals who want to maintain good brain function as they age.

The Institute encourages life-long relationships with its patients to support the establishment of healthy brain habits and to provide guidance when new illnesses develop that can impact the brain. In doing so, the research team is able to collect longitudinal data about the development and progression of brain diseases throughout the life cycle. This data is helping to advance understanding about the progression of diseases like Alzheimer’s, in which so much is still unknown.

Learn more about the Institute for Brain Health in this article.

The Research Institute:
Saving Lives Through Science
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The Massachusetts General Hospital Research Institute is the largest hospital-based research program in the United States, with a community of over 10,000 people working across more than 30 institutes, centers and departments.

Our researchers work side-by-side with physicians to pioneer the latest scientific advancements for curing disease and healing patients in Boston, across the United States and around the world.

To learn more about the Research Institute, please visit our website.

A Snapshot of Science: Detection of Alzheimer’s Disease, Development of Type 1 Diabetes, and Much More

We wanted to share some recent Mass General research that has been published in high impact, top-tier journals. This is just a small snapshot of the incredible research that takes place at Mass General each day — there’s lots more to find at massgeneral.org/research/news!

 

DETECTING AND TREATING STIFF TUMORS
Published in Nature Scientific Reports on August 14, 2017
(Summary submitted by Peter Caravan, PhD, of the Martinos Center for Biomedical Imaging)

In tumors, cancer cells are surrounded by a collection of proteins, enzymes, sugars, lipids, and minerals called the extracellular matrix (ECM). Many cancers have a fibrotic ECM, making the tumor stiff and preventing delivery of anti-cancer drugs. The presence of a fibrotic ECM is often associated with poor prognosis. We developed a new MRI method to detect tumor fibrosis non-invasively, and studied its effect in a mouse model of pancreatic cancer. The potential impact of this work is a new tool to stage the aggressiveness of tumors, guide treatment planning, and monitor the effectiveness of new tumor ECM altering treatments.

 

IMPACT OF BLOOD AND URINE FILTRATION IN LEAKY KIDNEY FILTERS
Published in Scientific Reports on August 16, 2017
(Summary submitted by Hua A. Jenny Lu, MD, PhD, of the Nephrology Division)

One major function of the kidney is filtering blood through an intricate “glomerular filter”. Disruption of any components of this highly sophisticated and dynamic filter’s structure leads to proteinuria (protein in the urine), a condition frequently seen in diabetic nephropathy and many other glomerular diseases. How blood filters though the glomerular filter and how proteinuria develops when the filter becomes leaky has not been well understood. This paper reports the application of a novel and powerful scanning microscopy technology, the Helium Ion microscopy (HIM) to identify previously unrecognized ultrastructural abnormalities of proteinuric glomerulopathy in animals. These newly discovered abnormalities provide important insight into the molecular and cellular mechanism underlying proteinuria kidney diseases.

 

OBSERVING THE DEVELOPMENT OF TYPE 1 DIABETES
Published in PNAS on August 24, 2017
(Summary submitted by Ralph Weissleder, MD, PhD, Director of the Center for Systems Biology)

Type 1 diabetes (T1D) is an autoimmune disease where insulin-producing cells are destroyed. Inflammation in islets of human patients has been hard to evaluate, given the challenging access to material. Now, our research team has discovered how the different cellular players interact. We created new reporter mice and new imaging agents where cells of interest (lymphocytes, macrophages, dendritic cells, beta cells) are fluorescent and can be observed by imaging. We were able to observe the intricate “dance” of different immune cells interacting with each other as diabetes develops. Throughout the process, Tregs (a unique type of T-lymphocyte) control the activation of many cell types. The “dynamic geography” of events uncovered here provide important clues to immunoregulation that underlies diabetes development.

 

NON-INVASIVE MEASUREMENT OF BRAIN ACTIVITY AND MEMORY ENCODING
Published in Scientific Reports on August 25, 2017
(Summary submitted by Meryem Yucel, PhD, of the Martinos Center for Biomedical Imaging)

Alzheimer’s disease (AD) is the most frequent cause of severe memory loss in the elderly. Early detection of AD is the key to preventing, slowing or stopping the disease. Near-infrared spectroscopy (NIRS) is a non-invasive neuroimaging technique capable of monitoring brain activation. Here, we investigated the utility of fNIRS in measuring the brain activity of healthy adults during memory encoding and retrieval under a face-name paired-associate learning task. Their study demonstrates that fNIRS can robustly measure memory encoding and retrieval-related brain activity. Future work will include similar measurements in populations with progressing memory deficits. Their approach, if successful, will introduce a non-invasive, inexpensive and easily accessible tool for identifying early stages of AD.