Research at Mass General

Massachusetts General Hospital is home to the largest hospital-based research enterprise in the U.S., with an annual budget of over $928 million in 2018.

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Snapshot of Science is a monthly digest of publication summaries, press releases and blog posts featuring researchers from Massachusetts General Hospital.

Welcome to the January 2018 edition of Snapshot of Science. Here's a quick look at some recent publications, press releases and stories about the Mass General research community.

In this issue we highlight:

  • 22 new studies published in high impact journals, along with 19 summaries submitted by the research teams
  • 5 new research-related press releases from the Mass General Public Affairs office
  • 11 posts from the Mass General Research Institute blog

Publications List

*Author-submitted summaries available when indicated

TESTING FEASIBILITY OF TOBACCO CONTROL PROGRAM
Implementing Tobacco Control Assistance in Pediatric Departments of Chinese Hospitals: A Feasibility Study
Abdullah AS, Guangmin N, Kaiyong H, Jing L, Yang L, Zhang Z, Winickoff JP
Published in the January edition of Pediatrics | *Summary available

PARENTS' ATTITUDES TOWARDS SMOKING BANS AND CHILD EXPOSURE TO SMOKE
Adult Attitudes and Practices Regarding Smoking Restrictions and Child Tobacco Smoke Exposure: 2000 to 2015
McMillen R, Wilson K, Tanski S, Klein JD, Winickoff JP
Published in the January edition of Pediatrics | *Summary available

MULTI-TRAIT ANALYSIS OF GENOME-WIDE ASSOCIATION STUDIES
Multi-Trait Analysis of Genome-Wide Association Summary Statistics Using MTAG
Turley P, Walters RK, Maghzian O, Okbay A, Lee JJ, Fontana MA, [et al.] Cesarini D, Neale BM, Benjamin DJ
Published in Nature Genetics on January 1, 2018 | *Summary available

IDENTIFICATION OF A MODIFIER THAT ALTERS CELLS’ RESPONSE TO DNA DAMAGE AND SENSITIZES CANCER CELLS TO CHEMOTHERAPY
Noncanonical Agonist PPARγ Ligands Modulate the Response to DNA Damage and Sensitize Cancer Cells to Cytotoxic Chemotherapy
Khandekar MJ, Banks AS, Laznik-Bogoslavski D, White JP, Choi JH, Kazak L, [et al.] Spiegelman BM
Published in PNAS on January 2, 2018

IDENTIFICATION OF BLOOD MARKERS THAT INDICIATE DANGEROUS NARROWING OF HEART VALVE
Association of Acylcarnitines With Left Ventricular Remodeling in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
Elmariah S, Farrell LA, Furman D, Lindman BR, Shi X, Morningstar JE, Rhee EP, Gerszten RE
Published in JAMA Cardiology on January 3, 2018 | *Summary available

INVESTIGATING THE ACTIVITY AND PRESENCE OF GUT MICROORGANISMS
Dynamics of Metatranscription in the Inflammatory Bowel Disease Gut Microbiome
Schirmer M, Franzosa EA, Lloyd-Price J, McIver LJ, Schwager R, Poon TW, [et al.] Xavier RJ, Huttenhower C
Published in Nature Microbiology on January 8, 2018 | *Summary available

ANALYZING VIRUS-LIKE PARASITES IN THE GENOME
Dissection of Affinity Captured LINE-1 Macromolecular Complexes
Taylor MS, Altukhov I, Molloy KR, Mita P, Jiang H, Adney EM, [et al.] LaCava J
Published in eLife on January 8, 2018 | *Summary available

UNCOVERING PATHWAYS THAT LEAD TO HEART FAILURE
Association of Cardiovascular Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction
de Boer RA, Nayor M, deFilippi CR, Enserro D, Bhambhani V, Kizer JR, [et al.] Ho JE
Published in JAMA Cardiology on January 10, 2018 | *Summary available

EVALUATING HEART VESSELS FOR THE PRESENCE OF BLOCKAGES AND HIGH-RISK/VULNERABLE CORONARY PLAQUE
Use of High-Risk Coronary Atherosclerotic Plaque Detection for Risk Stratification of Patients With Stable Chest Pain
Ferencik M, Mayrhofer T, Bittner DO, Emami H, Puchner SB, Lu MT, [et al.] Hoffmann U
Published in JAMA Cardiology on January 10, 2018 | *Summary available

REPEAT PROTEINS FOUND IN ALS AND DEMENTIA
CUG Initiation and Frameshifting Enable Production of Dipeptide Repeat Proteins from ALS/FTD C9ORF72 Transcripts
Tabet R, Schaeffer L, Freyermuth F, Jambeau M, Workman M, Lee CZ, [et al.] Martin F, Lagier-Tourenne C
Published in Nature Communications on January 11, 2018 | *Summary available

ISOLATING AND PROFILING TUMOR-DERIVED EXTERNAL VESICLES
Engineered Nanointerfaces for Microfluidic Isolation and Molecular Profiling of Tumor-Specific Extracellular Vesicles
Reátegui E, van der Vos KE, Lai CP, Zeinali M, Atai NA, Aldikacti B, [et al.] Stott SL
Published in Nature Communications on January 12, 2018 | *Summary available

UNDERSTANDING THE FUNCTIONS AND ECOLOGY OF THE MICROBIOME
Metatranscriptome of Human Faecal Microbial Communities in a Cohort of Adult Men
Abu-Ali GS, Mehta RS, Lloyd-Price J, Mallick H, Branck T, Ivey KL, [et al.] Chan AT, Huttenhower C
Published in Nature Microbiology on January 15, 2018 | *Summary available

CHARACTERIZING THE STABILITY OF THE GUT MICROBIOME
Stability of the Human Faecal Microbiome in a Cohort of Adult Men
Mehta RS, Abu-Ali GS, Drew DA, Lloyd-Price J, Subramanian A, Lochhead P, [et al.] Huttenhower C, Chan AT
Published in Nature Microbiology on January 15, 2018 | *Summary available

EXPLORING MECHANISM INVOLVED IN HUMAN IMMUNE-RESPONSE
Tuning of In Vivo Cognate B-T Cell Interactions by Intersectin 2 is Required for Effective Anti-Viral B Cell Immunity
Burbage M, Gasparrini F, Aggarwal S, Gaya M, Arnold J, Nair U, [et al.] Batista FD
Published in eLife on January 16, 2018 | *Summary available

TREATMENT OF A BLISTERING DISORDER
Variable Response to Naltrexone in Patients With Hailey-Hailey Disease
Cao S, Lilly E, Chen ST
Published in JAMA Dermatology on January 17, 2018 | *Summary available

HOW MRSA ALTERS THE BODY'S ABILITY TO FIGHT INFECTION
Methicillin-Resistant Staphylococcus Aureus Causes Sustained Collecting Lymphatic Vessel Dysfunction
Jones D, Meijer EFJ, Blatter C, Liao S, Pereira ER, Bouta EM, [et al.] Padera TP
Published in Science Translational Medicine on January 17, 2018 | *Summary available | See press release

EXPLORING AN UNEXPECTED SIDE EFFECT ASSOCIATED WITH A NEW TREATMENT FOR ACUTE MYELOID LEUKEMIA
Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of Mutant Isocitrate Dehydrogenase 2: Analysis of a Phase 1/2 Study
Fathi AT, DiNardo CD, Kline I, Kenvin L, Gupta I, Attar EC, Stein EM, de Botton S
Published in JAMA Oncology on January 18, 2018 | *Summary available

UNDERSTANDING LEARNING AND MEMORY FUNCTIONS IN A KEY BRAIN REGION
Multi-Modal Encoding of Novelty, Reward, and Learning in the Primate Nucleus Basalis of Meynert
Martinez-Rubio C, Paulk AC, McDonald EJ, Widge AS, Eskandar EN
Published in Journal of Neuroscience on January 18, 2018

TAU INDUCES DISTINCT CHANGES IN BLOOD VESSELS
Tau Induces Blood Vessel Abnormalities and Angiogenesis-Related Gene Expression in P301L Transgenic Mice and Human Alzheimer's Disease
Bennett RE, Robbins AB, Hu M, Cao X, Betensky RA, Clark T, Das S, Hyman BT
Published in PNAS on January 22, 2018

INVESTIGATING MECHANISMS OF B CELLS
Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells
Gaya M, Barral P, Burbage M, Aggarwal S, Montaner B, Warren Navia A, [et al.] Batista FD
Published in Cell on January 25, 2018 | *Summary available

COMPARING TREATEMENTS FOR PROSTATE CANCER
Comparison Between Adjuvant and Early-Salvage Postprostatectomy Radiotherapy for Prostate Cancer With Adverse Pathological Features
Hwang WL, Tendulkar RD, Niemierko A, Agrawal S, Stephans KL, Spratt DE, [et al.] Efstathiou JA
Published in JAMA Oncology on January 25, 2018 | *Summary available

NEW ENDOSCOPE TECHNOLOGY
High-speed Optical Coherence Tomography by Circular Interferometric Ranging
Siddiqui M, Nam AS, Tozburun S, Lippok N, Blatter C, Vakoc BJ
Published in Nature Photonics on January 26, 2018 | *Summary available

Publication Summaries

1. TESTING FEASIBILITY OF TOBACCO CONTROL PROGRAM
Implementing Tobacco Control Assistance in Pediatric Departments of Chinese Hospitals: A Feasibility Study
Abdullah AS, Guangmin N, Kaiyong H, Jing L, Yang L, Zhang Z, Winickoff JP
Published in the January edition of Pediatrics

A comprehensive tobacco control program, the Clinical Effort Against Secondhand Smoke Exposure (CEASE), has been shown to be effective within the United States to provide assistance to parents to quit smoking and reduce children’s exposure to SHS. A modified version of this evidence-based program was developed and pilot-tested for use in the pediatric inpatient setting within China. The CEASE-China intervention was effective at facilitating system-level changes in tobacco control within the hospital setting and showed significant increases in the delivery of assistance to parents who smoke and parental behaviors to reduce children’s exposure to secondhand smoke.

(Summary submitted by Jeremy Drehmer, MPH, CPH, of the Mass General for Children)

2. PARENTS' ATTITUDES TOWARDS SMOKING BANS AND CHILD EXPOSURE TO SMOKE
Adult Attitudes and Practices Regarding Smoking Restrictions and Child Tobacco Smoke Exposure: 2000 to 2015
McMillen R, Wilson K, Tanski S, Klein JD, Winickoff JP
Published in the January edition of Pediatrics

The U.S. Social Climate Survey of Tobacco Control was used to examine changes in smoking bans and delivery of tobacco control assistance in the pediatric setting from 2000 to 2015. More parents protect their children from tobacco smoke in the home and car and adults are more supportive of smoke-free public places, yet 1 in 5 households still permit smoking indoors and half of the U.S. population remains unprotected by smoke-free laws inside hospitality venues. There were significant improvements in the rates of assisting parents who smoke in the pediatric setting, yet one-third remain not screened for tobacco use.

(Summary submitted by Jeremy Drehmer, MPH, CPH, of the Mass General for Children)

3. MULTI-TRAIT ANALYSIS OF GENOME-WIDE ASSOCIATION STUDIES
Multi-Trait Analysis of Genome-Wide Association Summary Statistics Using MTAG
Turley P, Walters RK, Maghzian O, Okbay A, Lee JJ, Fontana MA, [et al.] Cesarini D, Neale BM, Benjamin DJ
Published in Nature Genetics on January 1, 2018

Gathering genetic data is expensive, making limited sample size the primary obstacle to making discoveries in genetic studies. To address this issue, we have developed a new method called MTAG that leverages studies of related traits to accelerate the rate of discovery using only existing data. By applying MTAG to depressive symptoms, neuroticism, and subjective well-being, we have discovered dozens of new genetic loci associated with each trait and substantially increased the ability to predict these traits in the population.

(Summary submitted by Patrick Turley, PhD, of the Department of Medicine)

4. IDENTIFICATION OF BLOOD MARKERS THAT INDICIATE DANGEROUS NARROWING OF HEART VALVE
Association of Acylcarnitines With Left Ventricular Remodeling in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
Elmariah S, Farrell LA, Furman D, Lindman BR, Shi X, Morningstar JE, Rhee EP, Gerszten RE
Published in JAMA Cardiology on January 3, 2018

Aortic stenosis is a disorder predominantly affecting the elderly that is characterized by severe narrowing of the aortic valve, the doorway through which blood exits the heart. Aortic stenosis ultimately leads to heart failure and death. Surgical replacement of the valve is curative, but surgery is routinely reserved until the heart begins to fail. For many patients, this point is too late. We have identified compounds within the blood that reflect the heart's struggling to overcome the aortic stenosis. Levels of these compounds also improve once the diseased aortic valve is replaced, signifying the lessened workload on the heart. These blood markers may ultimately prove to be valuable in helping physicians plan the optimal timing of valve replacement surgery.

(Summary submitted by Sammy Elmariah, MD, MPH, of the Department of Cardiology and Medicine)

5. INVESTIGATING THE ACTIVITY AND PRESENCE OF GUT MICROORGANISMS
Dynamics of Metatranscription in the Inflammatory Bowel Disease Gut Microbiome
Schirmer M, Franzosa EA, Lloyd-Price J, McIver LJ, Schwager R, Poon TW, [et al.] Xavier RJ, Huttenhower C
Published in Nature Microbiology on January 8, 2018

Over the past decade, investigators have to come to realize that the gut microbiome plays a central role in Inflammatory Bowel Disease (IBD) development and progression. The relationship between variations in gut microbial communities and aberrant immune responses, however, remains enigmatic, and therefore has been a focus of study. The Human Microbiome Project is an attempt to understand how dynamic fluctuations in the microbiome affect IBD pathophysiology by collecting and analyzing longitudinal data of over 100 individuals over 1 year. In this study, we present the first results from this initiative, and in turn discover that it is not only abundance of bacterial populations, but also their activity that play a critical role in IBD phenotypic variation.

(Summary submitted by Ramnik Xavier, MD, PhD, of the Department of Medicine and Gastroenterology)

6. ANALYZING VIRUS-LIKE PARASITES IN THE GENOME
Dissection of Affinity Captured LINE-1 Macromolecular Complexes
Taylor MS, Altukhov I, Molloy KR, Mita P, Jiang H, Adney EM, [et al.] LaCava J
Published in eLife on January 8, 2018

Approximately 2/3 of the genome is hundreds of thousands of copies of “repeat” DNA sequences, made throughout evolution by virus-like parasites called transposons. LINE-1 is the only remaining active transposon in humans; it continues to expand by “copying and pasting” itself to new locations, and in doing so contributes to cancer, aging, and genetic disease. We have limited understanding of our cells’ complex network of defenses against LINE-1 and how and when LINE-1 evades our defenses. We carried out a series of experiments designed to understand what host proteins and RNAs LINE-1 coopts for its own purposes, where and how it interacts with these host factors, and what these interactions mean for the lifecycle. We identified distinct LINE-1 populations in the cell’s cytoplasm and nucleus and propose that LINE-1’s entry into the nucleus occurs when cells divide during mitosis.

(Summary submitted by Martin Taylor, MD, PhD, of the Department of Pathology)

7. UNCOVERING PATHWAYS THAT LEAD TO HEART FAILURE
Association of Cardiovascular Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction
de Boer RA, Nayor M, deFilippi CR, Enserro D, Bhambhani V, Kizer JR, [et al.] Ho JE
Published in JAMA Cardiology on January 10, 2018

There are two main subtypes of heart failure (HF) - HFpEF and HFrEF. Currently many proven therapies to treat HFrEF exist; by contrast, no effective treatments for HFpEF have been found, yet, half of all patients with HF have HFpEF. In the study, we demonstrate that different pathways including neurohormonal activation, cardiac injury, inflammation, and kidney dysfunction measured by circulating biomarkers contribute to the future development of HFrEF. By contrast, far fewer known pathways assessed by biomarkers seemed related to HFpEF. This study underscores how much remains to be uncovered about pathways leading to HFpEF as a complex and heterogeneous disease.

(Summary submitted by Jennifer Ho, MD, of the Department of Cardiology and Medicine)

8. EVALUATING HEART VESSELS FOR THE PRESENCE OF BLOCKAGES AND HIGH-RISK/VULNERABLE CORONARY PLAQUE
Use of High-Risk Coronary Atherosclerotic Plaque Detection for Risk Stratification of Patients With Stable Chest Pain
Ferencik M, Mayrhofer T, Bittner DO, Emami H, Puchner SB, Lu MT, [et al.] Hoffmann U
Published in JAMA Cardiology on January 10, 2018

We studied 4400 patients from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial and used cardiac computed tomography (CAT) scans to evaluate heart vessels (coronary arteries) for the presence of blockages and high-risk/vulnerable coronary plaque (accumulation of cholesterol in the vessel wall that is prone to rupture and can cause heart attack). We found that both vessel narrowing and the presence of high-risk/vulnerable plaque increased the risk of future heart attack or death from heart disease. These results emphasize the need for evaluating CAT scans for the presence of high-risk plaque and tailoring the preventative therapies for patients even though no significant blockages were found.

(Summary submitted by Maros Ferencik, MD, PhD, of the Department of Radiology)

9. REPEAT PROTEINS FOUND IN ALS AND DEMENTIA
CUG Initiation and Frameshifting Enable Production of Dipeptide Repeat Proteins from ALS/FTD C9ORF72 Transcripts
Tabet R, Schaeffer L, Freyermuth F, Jambeau M, Workman M, Lee CZ, [et al.] Martin F, Lagier-Tourenne C
Published in Nature Communications on January 11, 2018

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are devastating neurodegenerative disorders. The most frequent cause of inherited ALS and FTD is an abnormal repetition of a DNA motif (G4C2) in the C9ORF72 gene. The number of G4C2 repeats is normally lower than 30 but can extend to several hundred repeats in ALS/FTD patients. In this study, we determined the mechanisms leading to the abnormal production of proteins from expended repeats. These proteins (called dipeptide repeat proteins) aggregate in patients’ cells and play a central role in neurodegeneration due to C9ORF72 expansions. Our findings represent a crucial step for the development of therapeutic approaches for patients with C9ORF72 ALS/FTD.

(Summary submitted by Clotilde Lagier-Tourenne, MD, PhD, of the Department of Neurology)

10. ISOLATING AND PROFILING TUMOR-DERIVED EXTERNAL VESICLES
Engineered Nanointerfaces for Microfluidic Isolation and Molecular Profiling of Tumor-Specific Extracellular Vesicles
Reátegui E, van der Vos KE, Lai CP, Zeinali M, Atai NA, Aldikacti B, [et al.] Stott SL
Published in Nature Communications on January 12, 2018

Extracellular vesicles (EVs) are tiny particles released from all cells in the human body that carry RNA, DNA, proteins, and lipids. Specifically, EVs from cancer cells have the potential to be provide valuable molecular information about the cancer and how it’s responding to treatment. However, a lack of methods to isolate tumor-specific EVs from healthy EVs has limited their clinical use. We address this challenge through the development of a microfluidic approach that isolates tumor-specific EVs in glioblastoma patients. Our device achieved 94% specificity for tumor EV capture and identified mutations and genes that are hallmarks of the disease. This technology can be readily expanded to many different cancers and used to explore the underlying biology of metastasis.

(Summary submitted by Shannon Stott, PhD, of the Department of Medicine)

11. UNDERSTANDING THE FUNCTIONS AND ECOLOGY OF THE MICROBIOME
Metatranscriptome of Human Faecal Microbial Communities in a Cohort of Adult Men
Abu-Ali GS, Mehta RS, Lloyd-Price J, Mallick H, Branck T, Ivey KL, [et al.] Chan AT, Huttenhower C
Published in Nature Microbiology on January 15, 2018

The gut microbiome, the population of microbes living in the large intestine, is intimately related to human health, but there are still outstanding questions about the functions and ecology of the microbiome. We collected stool samples from more than 300 elderly men in the Health Professionals Follow-Up Study. Using metagenomic sequencing, we could see which microbes were present, and metatranscriptomic sequencing data informed us as to their expressed activity and function. We found that individuals have a core set of transcriptomic processes responsible for “housekeeping” physiologic functions that are universally expressed but often by different processes alongside more “specialized processes” that are more personalized and responsive to environmental triggers.

(Summary submitted by Andrew Chan, MD, MPH, of the Department of Medicine and Gastroenterology)

12. CHARACTERIZING THE STABILITY OF THE GUT MICROBIOME
Stability of the Human Faecal Microbiome in a Cohort of Adult Men
Mehta RS, Abu-Ali GS, Drew DA, Lloyd-Price J, Subramanian A, Lochhead P, [et al.] Huttenhower C, Chan AT
Published in Nature Microbiology on January 15, 2018

Characterizing the stability of the gut microbiome (the population of microbes living in the large intestine) is important in order to exploit it as a therapeutic target and diagnostic biomarker. We collected multiple stool samples from more than 300 elderly men in the Health Professionals Follow-Up Study and performed a longitudinal assessment of microbial dynamics over a 6-month period. We looked at which microbes were present (called metagenomes), and their activity and function (called metatranscriptomes). Our results support single-time point assessment as a representative measure of a person’s microbiome using metagenomes which remained consistent over time. However, multiple time point assessments may be needed to accurately measure metatranscriptome elements which were much more variable.

(Summary submitted by Andrew Chan, MD, MPH, of the Department of Medicine and Gastroenterology)

13. EXPLORING MECHANISM INVOLVED IN HUMAN IMMUNE-RESPONSE
Tuning of In Vivo Cognate B-T Cell Interactions by Intersectin 2 is Required for Effective Anti-Viral B Cell Immunity
Burbage M, Gasparrini F, Aggarwal S, Gaya M, Arnold J, Nair U, [et al.] Batista FD
Published in eLife on January 16, 2018

The immune system defends the body by generating antibodies that recognize and destroy infectious agents. The impairment of B cells - one component of the immune system - can result in the overgrowth of pathogens, lingering infections, or autoimmune diseases. Our work focuses on Intersectin 2, a protein implicated in Sjögren’s syndrome, a prevalent autoimmune disease. We show that Intersectin 2 is required for the generation of protective antibodies in response to viral infections and vaccination. Using a combination of genetics, microscopy and biochemistry, we have uncovered the mechanisms by which it impacts peak immunity.

(Summary submitted by Usha Raman Nair, PhD, of the Ragon Institute)

14. TREATMENT OF A BLISTERING DISORDER
Variable Response to Naltrexone in Patients With Hailey-Hailey Disease
Cao S, Lilly E, Chen ST
Published in JAMA Dermatology on January 17, 2018

Hailey-Hailey Disease (HHD) is an incurable genetic blistering skin disease. Patients often must try multiple treatment options but nothing works 100% of the time for everyone. Our study describes the successful use of naltrexone, a drug typically used for addiction medicine, to treat HHD. Our results present an interesting and new approach to skin disease that has only been reported a couple times before. We’re excited to describe a new way to treat this rare disease, in hopes that it helps improve other patients’ quality of life.

(Summary submitted by Steven Chen, MD, MPH, of the Department of Dermatology and Medicine)

15. EXPLORING AN UNEXPECTED SIDE EFFECT ASSOCIATED WITH A NEW TREATMENT FOR ACUTE MYELOID LEUKEMIA
Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of Mutant Isocitrate Dehydrogenase 2: Analysis of a Phase 1/2 Study
Fathi AT, DiNardo CD, Kline I, Kenvin L, Gupta I, Attar EC, Stein EM, de Botton S
Published in JAMA Oncology on January 18, 2018

IDH mutations were recently discovered in a subset of patients with acute myeloid leukemia (AML). IDH inhibitors can block the altered IDH protein, leading to impressive therapeutic response in some patients. One such IDH2 inhibitor, enasidenib, was recently approved by the FDA. In a recent study of AML patients receiving enasidenib, we found that approximately 12% of patients experienced an inflammatory condition called isocitrate dehydrogenase differentiation syndrome (IDH-DS). IDH-DS can be severe and life-threatening, and requires appropriate management, which includes the use of steroids and, if persistent and severe enough, a pause in therapy. These findings are important for the care of patients receiving this new class of IDH inhibiting drugs.

(Summary submitted by Amir Fathi, MD, of the Department of Hematology/Oncology and Medicine)

16. HOW MRSA ALTERS THE BODY'S ABILITY TO FIGHT INFECTION
Methicillin-Resistant Staphylococcus Aureus Causes Sustained Collecting Lymphatic Vessel Dysfunction
Jones D, Meijer EFJ, Blatter C, Liao S, Pereira ER, Bouta EM, [et al.] Padera TP
Published in Science Translational Medicine on January 17, 2018

14 million people develop bacterial infections in their skin and soft tissues each year in the US. Many of these patients will endure repeated infections over the subsequent months and years. About 40% of these infections are due to a difficult to treat bacteria called methicillin-resistant Staphylococcus aureus (MRSA). Lymphatic vessels are critical to clearing infections and stimulating immune responses. Our study shows that MRSA infections permanently impair lymphatic function, potentially explaining why many patients have recurrent infections. Our discovery will facilitate the development of drugs to maintain lymphatic function during and after MRSA infections, ultimately protecting patients from future infections.

(Summary submitted by Timothy Padera, PhD, of the Department of Radiation Oncology)

17. INVESTIGATING MECHANISMS OF B CELLS
Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells
Gaya M, Barral P, Burbage M, Aggarwal S, Montaner B, Warren Navia A, [et al.] Batista FD
Published in Cell on January 25, 2018

This paper describes a groundbreaking new model of early infection and immune response. We show the importance of NKT cells in the early activation of B cells in mice. NKT cells are the main producers of a molecular signal called IL-4, which triggers a reaction in B cells, causing them to form specialized structures in the lymph nodes that are crucial to immune response. This same process of B cell activation is visible in monkeys infected with Zika, suggesting that this newly discovered immune mechanism is essential to many animals—potentially including humans.

(Summary submitted by Facundo Batista, PhD, of the Ragon Institute)

18. COMPARING TREATEMENTS FOR PROSTATE CANCER
Comparison Between Adjuvant and Early-Salvage Postprostatectomy Radiotherapy for Prostate Cancer With Adverse Pathological Features
Hwang WL, Tendulkar RD, Niemierko A, Agrawal S, Stephans KL, Spratt DE, [et al.] Efstathiou JA
Published in JAMA Oncology on January 25, 2018

When surgical removal of the prostate (prostatectomy) fails to cure a prostate cancer patient, the next best step is postoperative radiation therapy. The debate now centers on the optimal timing of such post-prostatectomy radiation therapy. The findings from our study suggest that for patients who have risk factors for recurrence of their prostate cancer, using post-prostatectomy radiation therapy when their prostate-specific antigen (PSA) levels remain undetectable may confer greater benefit than surveillance followed by early-salvage radiation therapy (when the PSA is detectable). Ultimately, the onus is on the uro-oncology team to discuss postoperative radiation therapy with the patient, address its optimal timing when it is used, and provide justification when it is not.

(Summary submitted by Jason Efstathiou, MD, Dphil, of the Department of Radiation Oncology)

19. NEW ENDOSCOPE TECHNOLOGY
High-speed Optical Coherence Tomography by Circular Interferometric Ranging
Siddiqui M, Nam AS, Tozburun S, Lippok N, Blatter C, Vakoc BJ
Published in Nature Photonics on January 26, 2018

Endoscopes use cameras to visualize internal organs. However, these surface-imaging cameras miss many critical features buried within the tissue. To detect these features, optical microscopies can be used, but it is difficult to deploy existing microscopies to geometrically complex and/or dynamic sites. To address this challenge, we have developed circular-ranging optical coherence tomography – a high-resolution microscopy technique that is deployable to uncontrolled and complex settings. This technology may lead to the creation of three-dimensional endoscopic/laparoscopic cameras useful in a broad set of diagnostic and surgical procedures.

(Summary submitted by Benjamin Vakoc, PhD, of the Department of Dermatology)

Press Releases

X Chromosome Reactivation Could Treat Rett Syndrome, Other X-Linked Disorders
Featuring Lieselot Carrette, PhD, and Jeannie T. Lee, MD, PhD

A study from a team of Massachusetts General Hospital investigators points toward a potential strategy for treating X-linked disorders – those caused by mutations in the X chromosome – in females.

Improved Blood Stabilization Should Expand Use of Circulating Tumor Cell Profiling
Featuring Keith Wong, PhD, and Shannon Tessier, PhD

A new blood stabilization method, developed at the Massachusetts General Hospital Center for Engineering in Medicine, significantly prolongs the lifespan of blood samples for microfluidic sorting and transcriptome profiling of rare circulating tumor cells, living cancer cells carried in the bloodstream.

Mass. General Study Reveals How MRSA Infection Compromises Lymphatic Function
Featuring Timothy Padera, PhD

MGH investigators describe have found in mouse models that MRSA infection impairs the ability of lymphatic vessels to pump lymphatic fluid to lymph nodes, which may contribute to the frequent recurrences of MRSA infection experienced by patients.

Combination Chemotherapy May Significantly Improve Treatment for Deadly Brain Tumor
Featuring Bakhos Tannous, PhD

A team led by MGH investigators has found that adding the drug hydroxyurea to the current chemotherapy protocol for glioblastoma significantly increased survival in animal models.

People with Tetraplegia Gain Rapid Use of Brain-Computer Interface
Featuring Leigh Hochberg, MD, PhD

A new approach to calibrating the pioneering BrainGate brain-computer interface allowed three clinical trial participants with tetraplegia to gain control of a computer cursor after just one simple calibration step.

Blog Posts

Research Your Resolution: Use Food Placement to Set Yourself Up for Weight Loss Success
Featuring Anne Thorndike, MD, MPH

Does your new year's resolution include eating a healthier diet? Research from Mass General's Anne Thorndike has found that using food placement can encourage healthy eating choices.

Research Your Resolution: Reduce Your Risk of A Heart Attack
Featuring Sek Kathiresan, MD

Research from Massachusetts General Hospital's Sek Kathiresan tells us that DNA is not destiny. Following a healthy lifestyle can reduce your risk of a heart attack by almost 50%.

DASH Diet — Ranked Best Overall Diet, Could Prevent Hypertension and Gout
Featuring Hyon Choi, MD, DrPH

The DASH diet, which focuses on vegetables, fruits, whole grains, low-fat dairy, and lean proteins, was recently recognized by U.S. News and World Report as the best overall diet and was ranked No. 1 for preventing heart disease. In addition to lowering blood pressure, Mass General researchers have found that the diet may also reduce the risk of developing gout.

Research Your Resolution: Boost Your Brain Health With Social Connections
Featuring Joel Salinas, MD

Taking steps to boost brain health in 2018 could be as easy as calling a friend. Research from Massachusetts General Hospital's Joel Salinas finds that when we make social connections with other people, we live better and have healthier brains for longer.

Research Your Resolution: Take a Slow and Steady Approach to Losing Weight
Featuring Emily Feig, PhD

When it comes to weight loss, research from Mass General's Emily Feig has found that slow and steady is the key to success.

Early Treatment for ADHD May Lessen Risk of Substance Abuse Disorders
Featuring Timothy Wilens, PhD

Research from Massachusetts General Hospital's Timothy Wilens has found that youth/adolescents with ADHD are twice as likely to develop a substance abuse problem. Dr. Wilens' newest findings show that treating children with stimulant-based medication for ADHD before the age of 15 can significantly reduce their risk of abusing drugs or alcohol.

Research Your Resolution: Consider Heart Health Before Going Gluten-Free
Featuring Andrew Chan, MD, MPH

Research from Massachusetts General Hospital's Andrew Chan tells us what we should know about heart health before trying a gluten-free diet.

Research Your Resolution: Focus on Your Mental Health, Especially As You Age
Featuring Jennifer Gatchel, MD, PhD

According to Jennifer Gatchel, a geriatric psychiatrist and researcher at Mass General, dementia is not inevitable. Taking care of your mental health as you age could provide long-term benefits for your brain.

Research from Mass General Clinicians Highlights the Growing Opioid Problem and Its Impact on Health Outcomes
Featuring Zirui Song, MD, PhD, Efren Flores, MD, and Renata R. Almeida, MD, MSc

New research from Massachusetts General Hospital clinicians highlights the severity of the growing opioid epidemic and how everyone in healthcare has a role to play in helping patients with their illness.

Research Your Resolution: Maintain an Exercise Routine for Health Benefits Beyond Weight Loss
Featuring Fatima Cody Stanford, MD, MPH, MPA, FAAP, FACP, FTOS

Research from Massachusetts General Hospital's Fatima Cody Stanford has shown that keeping up with an exercise routine can help with weight maintenance, and can improve heart health, mood, and longevity.

Research Your Resolution: Reduce Your Stress and Anxiety with Meditation
Featuring Sara Lazar, PhD

Dr. Sara Lazar is an investigator in the Department of Psychiatry at Massachusetts General Hospital who is using brain imaging technology to measure the effects of meditation on brain structure. Her research has found that meditation can change neural connections and reduce stress.

Research Your Resolution: Use Evidence Based Resources to Quit Smoking in 2018
Featuring Nancy Rigotti, MD

What's the best way to kick a smoking habit? According to Mass General's Nancy Rigotti, the most effective method is to combine FDA-approved medications with coaching support to change smoking behavior.