Research Awards and Honors: November 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:

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Charumathi Baskaran, MD, of the Pediatric Endocrine Unit; Laura Dichtel, MD, of Neuroendocrinology; and Vibha Singhal, MD, of the Pediatric Endocrine Unit, were each honored with an Early Investigator Award from the Endocrine Society. Baskaran and Dichtel received their awards for endocrine research, and Singhal received his for metabolic bone research. The awards were established to recognize the achievement of early career investigators in endocrine research. The awardees be honored at the Endocrine Society’s 100th Annual Meeting & Expo next March in Chicago.

“It is a wonderful honor to have been selected as an Early Investigator Awardee through the Endocrine Society. Awards like this one are incredibly important to recognizing and supporting junior investigators as we build our independent research careers. I am grateful to the Endocrine Society for continuing this program of honoring and supporting young investigators. I am additionally grateful to Dr. Karen K. Miller, my research mentor here at MGH, who is truly dedicated to training the next generation of clinical researchers.” – Laura Dichtel, MD

“It was very encouraging to receive the Early investigator Award from the Endocrine Society. Not only did it provide funds for travel and meeting attendance but also provided the moral boost that keeps a young investigator like myself going. I am thankful for the opportunity to be working at MGH which amalgamates the best resources and mentorship. I am looking forward to making some contribution to advancing science.” – Vibha Singhal, MD

“As a member of the faculty at the Pediatric Endocrine Unit, my research focuses on investigating the impact of hormonal changes on mood and behavior in adolescents and young children.  This recognition in the from Endocrine society in the form of  ‘Early Investigator Award’ is a great honor and a big moral boost for me. Endocrine Society offers a platform for budding researchers like me to showcase our findings to their entire professional community. This award had opens up a whole new area of networking and will allow me to develop collaborations with the leading researchers in my areas of interest. The Early Investigator Award will enable advancement in my research career and will keep me motivated to pursue my goal against all odds.” – Charumathi Baskaran, MD


Cudkowicz.jpgMerit Cudkowicz, MD, chief of the Neurology Service, has received the American Academy of Neuromuscular and Electrodiagnostic Medicine Honorary Membership Award. This award recognizes a nonmember physician who is a major contributor to the field of Neuromuscular disease through teaching, research and/or scholarly
publications.

“I was honored to receive this lifetime award from the AANEM. Neuromuscular specialists are physicians who excel at both care and research of people with a large variety of disorders, including ALS. While not personally trained in electrodiagnostics, I have worked closely with my neuromuscular colleagues to develop new treatments and improve the care of people with ALS. Many neuromuscular physician scientists are leaders in clinical trials and are making a huge difference in the lives of our patients. I am proud to be part of this collaborative network of physicians and other healthcare providers.”


Daly.jpgMark Daly, PhD, chief of the Analytical and Translational Genetics Unit, has been named as one of the new members of the National Academy of Medicine. Election to the Academy is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service. New members are elected by current members through a process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care and public health.

“I am humbled and honored to receive this recognition and look forward to contributing to the National Academy of Medicine. Genetics today is truly a team sport and my part is just one of very many – therefore I am gratified not by the personal recognition, but that it reflects that our global, collaborative partnerships in genetic research are making real progress that will advance medicine.”


Walker.jpgMelissa Walker, MD, PhD, has received the 2017 Shields Research Grant from the Child Neurology Foundation. The award supports translational or basic research by a child neurologist or developmental pediatrician early in his/her academic career and who has developed clinical research skills and has a plan for further development of that research or has basic science research skills related to child neurology and who has a plan to translate the new knowledge into clinical care for children with neurologic diseases.

“I’m honored to receive the Shields Award to support my translational and basic science research in the laboratory of Dr. Vamsi Mootha. Primary Mitochondrial Disorders are a group of individually rare but collectively significant diseases exhibiting remarkable clinical and genetic heterogeneity. Currently, no reliable biomarkers or clinical tests exist for diagnosis or disease monitoring. We aim to develop a reliable, rapid, inexpensive, and noninvasive assay of mitochondrial function. As Director of the MGH Pediatric Mitochondrial Disorders Clinic, this award will allow me to conduct this potentially transformative work in a world-class laboratory while concurrently caring for affected patients.”

New Screening Technique Makes Waves in The Quest for Earlier Diagnosis of Alzheimer’s Disease

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How could the study of patients under anesthesia lead to a new way to diagnose Alzheimer’s disease? It could all come down to brainwaves.

Patrick Purdon, PhD, a researcher with the Massachusetts General Hospital Department of Anesthesia, Critical Care and Pain Medicine, is investigating how changes in brainwave patterns could potentially detect early signs of Alzheimer’s disease.

For the past decade, Purdon and his colleagues have been using electroencephalogram, called EEG, to measure the brainwaves of patients under sedation. That research has demonstrated that different anesthetic drugs produce distinct brainwave patterns in patients.  After finding these brainwave patterns in elderly patients under anesthesia were slower and smaller than those of younger adult patients, Purdon and colleagues examined the areas that were affected by age and discovered they align with brain areas that typically undergo degeneration in Alzheimer’s.

This led to an intriguing possibility—could EEG measurements be used as a diagnostic tool for Alzheimer’s disease?

With a grant from the NIH, Purdon is now studying the brainwave patterns of early Alzheimer’s patients, and monitoring how those brainwaves change over the progression of the disease.  Purdon and his team hope to determine whether EEG can provide a clearer picture of the process of neurodegeneration and changes in brain function.

If they’re successful, EEG could be used as an inexpensive alternative for screening of neurodegenerative problems, potentially leading to earlier diagnosis of Alzheimer’s disease, where treatments could be more effective at slowing or halting its progression. Brainwave measurements could also provide a more accurate measure of the disease’s progression over time.

Read the full story in Proto Magazine here.

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:

Crowdsourcing Cancer Research – Researchers at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital will be recruiting attendees at the annual Radiological Society of North America meeting next week to help them label tumors from an archive of images from the Cancer Imaging Archive. Once the tumors are identified, the images will help create new machine-learning based tool cancer diagnoses and prognosis.

Looking Back: Mass General and the Coconut Grove Fire – This Proto podcast talks about the role Mass General played in treating victims of the deadly Cocoanut Grove fire in Boston in 1942, in which 492 people died. The podcast features the story of a survivor who was treated at Mass General and an interview with surgeon John Schulz on how the fire led to innovations in burn care.

Study finds that 1 in 5 show symptoms of PTSD after cancer diagnosis – Roughly 1 in 5 cancer patients developed post-traumatic stress disorder within six months of their diagnosis—and a small percentage still experienced trauma-related symptoms six months later, according to new research in the journal Cancer. The study was conducted by a research team that included investigators from Boston (the Dana Farber Cancer Institute) and Malaysia.

Science in the House: A Live DJ/VJ experience inspired by particle physics – Check out highlights of a two performances from the Manchester Science Festival that combine electronic dance music with science themed visuals.

Top photo courtesy of the Martinos Center for Biomedical Imaging

Harvard Catalyst – A Great Resource for Researchers

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Established in 2008, Harvard Catalyst | The Harvard Clinical and Translational Science Center is dedicated to improving human health by enabling collaboration and providing tools, training, and technologies to clinical and translational investigators.

As a shared enterprise of the University, Harvard Catalyst is funded by the National Institutes of Health (NIH) Clinical and Translational Science Awards (CTSA) Program (grant UL1 TR001102),  Harvard University, and its affiliated healthcare centers. Resources are freely available to all Harvard faculty, regardless of institutional affiliation or academic degree.

Here are just a few of the resources they offer:

Find collaborators:
Harvard Catalyst Profiles is a nationally recognized search tool to find Harvard faculty by key terms and specializations.

Conduct a clinical study:
In-patient and out-patient facilities at BCH, BIDMC, BWH, and MGH; research nursing; coordination; nutrition; laboratory assays and other clinical research resources.

Enter a training program:
Advanced mentored training and research (KL2); a two year master’s degree program; and Grant Review and Support Program (GRASP).

Expedite a multi-site study:
Use SMART IRB to move your study forward.

Get advice:
Consultations available on biostatistics and research design, population health research, regulatory, and bioinformatics.

Receive pilot funding:
Opportunities have included childhood obesity, health disparities, advanced imaging, and advanced microscopy. Check pilot funding page for new opportunities.

Use Harvard Catalyst informatics tools:
Access de-identified patient data with SHRINE, and share research resources with other labs using eagle-i (eagle-i.net).

Take a course:
A complete portfolio of clinical and translational research education is offered throughout the year.

https://catalyst.harvard.edu/

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.

Celebrity Patients Bring Lupus into The Headlines, But Much Remains Unknown

This September, actress and singer Selena Gomez announced on Instagram that she underwent a kidney transplant as part of her treatment for lupus, an autoimmune disease in which a body’s immune system begins to attack its own tissues and organs.

Gomez and other celebrities such as Nick Cannon, Toni Braxton and Seal have publicly spoken out about their struggles with lupus, which affects 1.5 million Americans and over five million people worldwide. Despite these high-profile patients, the disease still remains a mystery to much of the general public and the scientific community.

To shed light on symptoms, causes and treatment options for the disease, April Jorge, MD, a research fellow in the rheumatology unit at Massachusetts General Hospital , recently gave a talk on “Understanding the Mystery of Lupus” at Mass General’s Maxwell and Eleanor Blum Patient and Family Learning Center.

What is Lupus and Who Does it Affect?

The immune system typically protects us against infections by forming antibodies that detect and respond to invading pathogens, such as viruses and harmful bacteria. However, Jorge explained that in patients with lupus, the body forms auto-antibodies that target the own body’s cells as if they were intruders.

Lupus is a non-contagious and non-infectious disease that is caused by a combination of environmental and genetic factors. Jorge said that at least 50 different genes contribute to an increased risk of developing the disease.

Lupus is more common in women, and in African Americans and Hispanic populations. Patients are typically diagnosed between the ages of 15 to 45 years.

Symptoms of Lupus

Symptoms of lupus include skin rashes, hair loss, sores in the mouth, foggy thinking, seizures, vision problems, joint pain, liver inflammation, inflammation in the lining of the lungs and heart, blood clots, fatigue, and fever, among others.

“People with lupus also have a higher risk of heart attacks and strokes, and can be at a greater risk of getting osteoporosis and depression,” said Jorge. Lupus can also damage internal organs, especially the kidneys. Up to 50 percent of patients with lupus develop lupus nephritis—an inflammation of the kidneys that can prevent them from functioning properly.

Jorge suggested patients look out for several symptoms that may be warning signs of kidney damage.

“There can be some signs like swelling in the legs or belly,” she said. “Sometimes, it’s picked up by doctors if the patient has high blood pressure.” Other lupus patients may not have any outward symptoms of kidney damage, which makes it important for them to undergo regular screenings.

Diagnosis

Jorge explained that the disease is so complex because signs and symptoms differ from person to person. Many times, symptoms of lupus overlap with those of other disorders. Hence, it takes an average of 6 years to obtain a lupus diagnosis.

Diagnosis is typically made by factoring in combination of symptoms, blood tests and other factors, such as impaired liver or kidney function as a result of inflammation.

Treatment

While there is no cure for lupus, it is possible to treat the symptoms with medications and lifestyle changes.

Pharmaceutical Options

Medications prescribed for treating lupus include Prednisone (a corticosteroid that acts as an immune suppressant), Hydroxychloroquine (a drug originally used to treat malaria) and other immunosuppressant medications.

Currently doctors and scientists are trying to identify new and more effective treatments for lupus with fewer side effects. Jorge is optimistic about new drugs on the horizon that could improve treatment options. She said that biologics (products derived from natural—rather than chemical—sources) target certain parts of the immune system and are some of the most effective medications for lupus.

“Belimumab (manufactured under the brand name Benlysta®), which is given either as an injection or through an IV infusion, is the first drug to be approved for lupus in 50 years,” said Jorge. “But in the next five to 10 years, there will be many more.”

Lifestyle Modifications

Lifestyle changes can also help manage the symptoms of lupus, such as:

  • Exercising regularly
  • Getting enough sleep
  • Eating a healthy diet with fruits, vegetables and lean meats
  • Avoiding excess sun exposure
  • Using sunscreen lotions with at least SPF 50 and wearing protective clothing
  • Avoiding tobacco, as studies have indicated that smoking can make the disease more severe and harder to control

Based on recent research findings, the same strict guidelines may not apply to alcohol consumption. Jorge is currently investigating the impact of alcohol use on risk of heart attacks and death in patients with lupus. The research team has found that patients with lupus who consume light to moderate alcohol intake have lower rates of heart attacks and overall mortality than those who do not consume any alcohol.

To learn more about Lupus, please visit the Lupus Foundation of America’s website.

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:

A New Study Finds Good News About Treating Addiction – Dr. John Kelly of the Recovery Research Institute at Massachusetts General Hospital talks about his new study and says there’s some good news when it comes to treating addiction.

‘Null’ Research Findings Aren’t Empty of Meaning. Let’s Publish Them – op-ed written by Mass General investigator and physician Anupam Jena, MD, PhD.

The Secret to Long Life? It May Lurk in the DNA of the Oldest Among Us

15 Really Good Things Happening in Science Right Now

How to Write Science Stories (Volume 1: Story Structure) 

Up-Goer Five Challenge: Explain Your Research Using the Ten Hundred Most Common Words

(top photo courtesy of STAT) 

Investigators Add New Insights to Lyme Disease Diagnosis and Treatment

tick.jpgWith the number of reported Lyme disease infections expected to reach record highs in 2017, Massachusetts General Hospital researchers are helping to meet the need for new diagnostic tools and treatments.

The work of John Branda, MD, and Allen Steele, MD, was recently featured on the Mass General Giving Website. Here is a brief summary of the article, which you can find in full here.

A New Test for Lyme Disease

Lyme disease is caused by the bacterium Borrelia burgdorferi (B. burgdorferi), which is transmitted to humans through the bite of an infected blacklegged tick, commonly known as a deer tick. The tick must be attached for 36 to 48 hours or more before the Lyme disease bacterium can be transmitted.

As with many infectious diseases, early detection plays a key role in treatment. John Branda, MD, associate director of the Clinical Microbiology Laboratory at Mass General, and his colleagues are developing a new way to diagnose Lyme disease, as current blood tests frequently yield false negative results in the weeks after infection.

The team’s new testing technique starts with a blood sample that is first amplified by polymerase chain reaction technology, a method that can make the genetic material of a pathogen such as B. burgdorferi more easily identifiable.

Then the blood is then scanned with magnetic resonance imaging, which can quickly pick up the Borrelia DNA. The test, known as T2MR, was able to detect B. burgdorferi in blood samples from patients who were suspected of having Lyme disease but had tested negative using traditional techniques.

Genetic Factors

In a separate research study, Allen Steere, MD, a Mass General rheumatologist and the researcher who led the team that first identified Lyme disease in the 1970s, is exploring why some patients do not recover from the disease even after receiving a course of antibiotics.

While the antibiotics are able to clear the infection, some patients still experience pain, fatigue and neurocognitive symptoms. A few patients can go on to suffer from antibiotic-refractory Lyme arthritis — a painful inflammation of the joints that long outlasts the infection.

In these patients, there is mounting evidence that Lyme disease triggers an abnormal immune response, which in turn attacks the tissues of the joints, even after B. burgdorferi has been cleared by antibiotics.

Dr. Steere believes that many more severe cases may result when people with a specific genetic profile encounter a particularly virulent strain of the bacterium.

When genetic susceptibility and virulent B. burgdorferi strains combine, as they do in as many as 20% of people of Caucasian ancestry who are infected with Lyme disease, ideal conditions are created for an amplified and maladaptive inflammatory response that can attack joint tissues.

To learn more about the symptoms and causes of Lyme disease, and for tips on protecting yourself from tick bites, please visit the Centers for Disease Control’s Lyme disease website.

A Snapshot of Science at Mass General: A New Approach to Targeted Cancer Treatments, Identifying Genes that Help Protect the Gut and Much More!

We wanted to share some recent Massachusetts General Hospital 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 on the Mass General website!


Cognitive Decline, Tau and β-Amyloid in Healthy Older Adults
(Summary submitted by Rachel Buckley, PhD, and Rebecca Amariglio, PhD, both of the Martinos Center for Biomedical Imaging)

We published findings from the Harvard Aging Brain Study (Department of Neurology, Massachusetts General Hospital) investigating the link between subjective memory complaints (when a patient reports a worsening of their thinking abilities, including memory) and Alzheimer’s disease pathology in individuals who are otherwise cognitively normal. We found that increasing memory complaints were linked with greater amounts of tau in the brain, a naturally occurring protein that is associated with neuron loss in Alzheimer’s disease. We posit that memory complaints are a very early marker of disease, as they relate to tau build up before clinical tests can detect memory impairment.

Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden
Buckley RF, Hanseeuw B, Schultz AP, Vannini P, Aghjayan SL, Properzi MJ, [et al.] Amariglio RE
Published in JAMA Neurology on October 2, 2017


New Approach to Targeted Cancer Treatment 
(Summary submitted by Conor L. Evans, PhD, of the Wellman Center for Photomedicine)

We have created a promising new light-activated, cancer-targeting therapeutic. Cancer drugs often cannot reach every cell in a tumor, leaving behind cells that can become resistant to treatment. At the same time, these drugs can cause unwanted systemic problems, such as weight and hair loss, elsewhere in the patient’s body. Our therapeutic was built to diffuse throughout tumors, target cancer cells, and kill these cells only when activated by light to avoid unwanted and burdensome side effects. We hope that this approach could one day find use in the fight against treatment-resistant cancers, like breast and lung.

An Integrin-Targeted, Highly Diffusive Construct for Photodynamic Therapy
Klein OJ, Yuan H, Nowell NH, Kaittanis C, Josephson L, Evans CL
Published in Scientific Reports on October 17, 2017


Identifying Genes that Help Protect the Gut 
(Summary submitted by Javier Elbio Irazoqui, PhD, formerly of the Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease)

The intestinal epithelium is a single layer of cells that protects the gut from environmental insult. Defects in this layer are linked to many diseases, including inflammatory bowel disease. Despite its critical importance, very little is known about the genes in the epithelium involved in this function. We found that transcription factor TFEB, a master regulator of lysosomal gene expression, provides a protective effect, and this function is mediated by expression of apolipoprotein A1, the major constituent of HDL, aka “good” cholesterol. Our findings suggest that enhancement of TFEB activity in the intestinal epithelium could be a therapeutic approach to enhance Apolipoprotein A1 expression for the treatment of inflammatory bowel disease.

Transcription Factor TFEB Cell-Autonomously Modulates Susceptibility to Intestinal Epithelial Cell Injury In Vivo
Murano T, Najibi M, Paulus GLC, Adiliaghdam F, Valencia-Guerrero A, Selig M, [et al.] Xavier RJ, Lassen KG, Irazoqui JE
Published in Scientific Reports on October 24, 2017


Patient Resistance to Immune Checkpoint Blockade Therapies
(Summary submitted by Nir Hacohen, PhD, of the Cancer Center)

Cancer therapy has been transformed in the last few years by immune-based therapies, called ‘checkpoint blockade’ therapies. An important question is why some people respond and others do not respond to this therapy. By analyzing the DNA of tumors from patients who developed resistance to checkpoint therapy, we found changes in the DNA of a key gene that is critical for tumors to be detected by the immune system. In this way, the tumor has learned how to hide from the immunotherapy. Knowing this will help us decide which patients would benefit from immune therapy. Finding ways to make these resistant tumors visible to the immune system is an important goal for the coming years.

Resistance to Checkpoint Blockade Therapy Through Inactivation of Antigen Presentation
Sade-Feldman M, Jiao YJ, Chen JH, Rooney MS, Barzily-Rokni M, Eliane JP, [et al.] Flaherty KT, Sullivan RJ, Hacohen N
Published in Nature Communications on October 26, 2017

World Diabetes Day 2017: Recent Diabetes Research from Massachusetts General Hospital

tumblr_inline_ofnq35sy4J1tq32mi_540.jpgDiabetes impacts an estimated 425 million people around the world, and that number is projected to rise to 693 million by 2045, according to the annual diabetes atlas released today by the International Diabetes Federation (IDF).

Diabetes develops as a result of having too much sugar in the blood. Over time, that imbalance can cause serious and costly health problems including heart disease, stroke, kidney disease and eye problems. The IDF diabetes atlas estimates that the world spends more than $720 billion on health care expenditures related to the disease.

November 14 marks World Diabetes Day – a day to raise awareness of the growing diabetes epidemic and the need for a cure as well as improved prevention and treatment methods.

Here are just a few examples of how Massachusetts General Hospital researchers are working to advance diabetes research and care:

  • Investigators have reason to believe that a vaccine originally used to treat tuberculosis could provide new hope for patients with type 1 diabetes.
  • People with type 2 diabetes are particularly prone to ulcers on the bottom of the foot, which can increase the risk of death and often result in a major amputation. Ulcers take months to heal, but a new discovery about mature B lymphocytes – best known for producing antibodies – could hasten wound recovery.
  • Researchers have developed a new method for measuring blood sugar levels in diabetes patients that could reduce testing errors by 50 percent.
  • Treatment guidelines for patients with type 1 diabetes have long called for yearly eye exams. But is there an alternative to this one-size-fits-all approach that could reduce patient burden and costs while providing a quicker diagnosis? Findings from a recent study lend insight into a possible new eye screening protocol.
  • Check out the Mass General Diabetes Unit, which seeks to advance the care of people with diabetes nearby and worldwide. U.S. News & World Report ranks Mass General Diabetes & Endocrinology among the best in the nation.