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 February 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:

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

Publications List

*Author-submitted summaries available when indicated

IDENTIFYING GENETIC CHANGES UNDERLYING COLITIS
C1orf106 is a Colitis Risk Gene That Regulates Stability of Epithelial Adherens Junctions
Mohanan V, Nakata T, Desch AN, Lévesque C, Boroughs A, Guzman G, [et al.] Lassen KG, Xavier RJ
Published in Science on February 1, 2018 | *Summary available | See press release

INVESTIGATING HEALTH CONSEQUENCES OF PLAYING IN THE NFL
Association Between Playing American Football in the National Football League and Long-term Mortality
Venkataramani AS, Gandhavadi M, Jena AB
Published in JAMA on February 1, 2018 | *Summary available

AMYLOID'S ROLE IN TAU ACCUMULATION AND MEMORY DECLINE
Structural Tract Alterations Predict Downstream Tau Accumulation in Amyloid-Positive Older Individuals
Jacobs HIL, Hedden T, Schultz AP, Sepulcre J, Perea RD, Amariglio RE, [et al.] Sperling RA, Johnson KA
Published in Nature Neuroscience on February 5, 2018 | *Summary available

RISK FOR STROKE IN PATIENTS WITH A HOLE IN THEIR HEART UNDERGOING SURGERY
Association of Preoperatively Diagnosed Patent Foramen Ovale With Perioperative Ischemic Stroke
Ng PY, Ng AK, Subramaniam B, Burns SM, Herisson F, Timm FP, [et al.] Eikermann M
Published in JAMA on February 6, 2018

ESTIMATING HEALTH OUTCOMES OF A LUNG CANCER SCREENING PROGRAM
Population Impact of Lung Cancer Screening in the United States: Projections From a Microsimulation Model
Criss SD, Sheehan DF, Palazzo L, Kong CY
Published in PLoS Medicine on February 7, 2018 | *Summary available

LOOKING AT PLAQUE IN PATIENTS WITH ACUTE CORONARY SYNDROME
Nonculprit Plaque Characteristics in Patients With Acute Coronary Syndrome Caused by Plaque Erosion vs Plaque Rupture: A 3-Vessel Optical Coherence Tomography Study
Sugiyama T, Yamamoto E, Bryniarski K, Xing L, Lee H, Isobe M, Libby P, Jang IK
Published in JAMA Cardiology on February 7, 2018 | *Summary available

OSTEOPOROSIS DRUG COULD HELP MULTIPLE MYELOMA PATIENTS WHO HAVE BONE DISEASE
Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Double-Dummy, Randomised, Controlled, Phase 3 Study
Raje N, Terpos E, Willenbacher W, Shimizu K, García-Sanz R, Durie B, [et al.] Roodman GD
Published in The Lancet Oncology on February 8, 2018 | *Summary available

CANCER DRUG DELAYS PROGRESSION OF TYPE OF PROSTATE CANCER
Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, [et al.] Small EJ
Published in New England Journal of Medicine on February 8, 2018 | See press release

NEW TREATMENT FOR PERIPHERAL NERVOUS SYSTEM TUMORS WITHOUT RISK OF HEARING LOSS
Targeting the cMET Pathway Augments Radiation Response Without Adverse Effect on Hearing in NF2 Schwannoma Models
Zhao Y, Liu P, Zhang N, Chen J, Landegger LD, Wu L, [et al.] Jain RK, Xu L
Published in PNAS on February 9, 2018 | *Summary available

PET IMAGING CAN TRACK BIOLOGICAL CHANGES ASSOCIATED WITH ALZHEIMER’S DISEASE
Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease
Quiroz YT, Sperling RA, Norton DJ, Baena A, Arboleda-Velasquez JF, Cosio D, [et al.] Johnson KA
Published in JAMA Neurology on February 12, 2018 | *Summary available

REPORT ON BENEFITS AND HARMS OF E-CIGARETTES
Balancing the Benefits and Harms of Electronic Cigarettes: A National Academies of Science, Engineering, and Medicine Report
Rigotti NA
Published in Annals of Internal Medicine on February 13, 2018 | *Summary available | See press release

DIFFERENTIATING KRAS PROTEINS' ROLE IN CANCER
Differential Effector Engagement by Oncogenic KRAS
Yuan TL, Amzallag A, Bagni R, Yi M, Afghani S, Burgan W [et al.], Benes CH, McCormick F
Published in Cell Reports on February 13, 2018 | *Summary available

PREDICTING SUCCESS OF FECAL MICROBIOTA TRANSPLANTATION
Strain Tracking Reveals the Determinants of Bacterial Engraftment in the Human Gut Following Fecal Microbiota Transplantation
Smillie CS, Sauk J, Gevers D, Friedman J, Sung J, Youngster I, [et al.] Xavier RJ, Alm EJ
Published in Cell Host and Microbe on February 14, 2018

DIGITAL MONITORING MAY HELP IDENTIFY PATIENTS LIKELY TO BENEFIT FROM IMMUNE CHECKPOINT THERAPY
Molecular Signatures of Circulating Melanoma Cells for Monitoring Early Response to Immune Checkpoint Therapy
Hong X, Sullivan RJ, Kalinich M, Kwan TT, Giobbie-Hurder A, Pan S [et al.] Toner M, Isselbacher KJ, Maheswaran S, Haber DA
Published in PNAS on February 16, 2018 | *Summary available

EARLY CONSULTATION WITH A DERMATOLOGIST CAN IMPROVE OUTCOMES IN PATIENTS WITH SUSPECTED CELLULITIS
Effect of Dermatology Consultation on Outcomes for Patients With Presumed Cellulitis: A Randomized Clinical Trial
Ko LN, Garza-Mayers AC, St John J, Strazzula L, Vedak P, Shah R, [et al.] Kroshinsky D
Published in JAMA Dermatology on February 16, 2018 | *Summary available

HOUSING PROBLEMS FOUND TO BE COMMON AT COMMUNITY HEALTH CENTERS
Prevalence of Housing Problems Among Community Health Center Patients
Baggett TP, Berkowitz SA, Fung V, Gaeta JM
Published in JAMA on February 20, 2018 | *Summary available | See press release

IMPROVING SHARED DECISION MAKING AMONG MINORITY POPULATIONS
Effectiveness of the DECIDE Interventions on Shared Decision Making and Perceived Quality of Care in Behavioral Health With Multicultural Patients: A Randomized Clinical Trial
Alegria M, Nakash O, Johnson K, Ault-Brutus A, Carson N, Fillbrunn M, [et al.] Shrout PE
Published in JAMA Psychiatry on February 21, 2018 | *Summary available

IDENTIFICATION OF GENETIC DEFECT THAT MAY CAUSE RARE MOVEMENT DISORDER
Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly
Aneichyk T, Hendriks WT, Yadav R, Shin D, Gao D, Vaine CA, [et al.] Bragg C, Talkowski ME
Published in Cell on February 22, 2018 | *Summary available | See press release

EXPLANATION FOR INITIAL TAU AGGREGATION IN BRAIN
Tau Protein Liquid-Liquid Phase Separation Can Initiate Tau Aggregation
Wegmann S, Eftekharzadeh B, Tepper K, Zoltowska KM, Bennett RE, Dujardin S, [et al.] Hyman BT
Published in The EMBO Journal on February 22, 2018 | *Summary available

EXPLORING THE IMPACT OF CHROMOSOME NUMBER ON HEART'S ABILITY TO REGENERATE
Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish
González-Rosa JM, Sharpe M, Field D, Soonpaa MH, Field LJ, Burns CE, Burns CG
Published in Developmental Cell on February 26, 2018 | *Summary available

ALTERNATIVE IMAGING CONTRAST AGENTS
Chiral DOTA Chelators as an Improved Platform for Biomedical Imaging and Therapy Applications
Dai L, Jones CM, Chan WTK, Pham TA, Ling X, Gale EM, [et al.] Anderson CJ, Caravan P, Law GL
Published in Nature Communications on February 27, 2018 | *Summary available

NEW MRI METHOD
Magnetic Resonance Mediated Radiofrequency Ablation
Hue YK, Guimaraes AR, Cohen O, Nevo E, Roth A, Ackerman JL
Published in the February issue of IEEE Transactions on Medical Imaging| *Summary available

Publication Summaries

1. IDENTIFYING GENETIC CHANGES UNDERLYING COLITIS
C1orf106 is a Colitis Risk Gene That Regulates Stability of Epithelial Adherens Junctions
Mohanan V, Nakata T, Desch AN, Lévesque C, Boroughs A, Guzman G, [et al.] Lassen KG, Xavier RJ
Published in Science on February 1, 2018

Ulcerative colitis (UC) is a debilitating inflammatory disease caused by both genetic and environmental factors. Impaired intestinal barrier function (“leaky gut”) has been observed in patients with UC and in healthy family members of some patients, suggesting a genetic component might underlie this phenomenon. However, it is poorly understood if and how genetic polymorphisms linked with UC alter the integrity of the intestinal barrier. Our study identifies the mechanism by which a genetic change to a single protein called C1ORF106 can alter the junctions that connect cells to form the lining of the gut. Maintaining precise control over these junctions is critical to intestinal function.

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

2. INVESTIGATING HEALTH CONSEQUENCES OF PLAYING IN THE NFL
Association Between Playing American Football in the National Football League and Long-term Mortality
Venkataramani AS, Gandhavadi M, Jena AB
Published in JAMA on February 1, 2018

Concerns have recently been raised around the health consequences of participating in professional football, but studying these effects has proven difficult because there are few good comparison groups to elite athletes. In this study, professional football players were compared to a cohort of individuals who briefly participated in the National Football League (NFL) during a three-game player strike in 1987. NFL players were found to have a higher mortality risk than replacement players, though the small number of deaths in the sample preclude definitive conclusions. These findings should motivate further follow-up of NFL and replacement players over time, as well as studies using similar natural experiments at other levels of participation in the sport (such as during high school or college).

(Summary submitted by Anupam B. Jena, MD, PhD, of the Department of Medicine and Atheendar S. Venkataramani, MD, PhD, of the University of Pennsylvania)

3. AMYLOID'S ROLE IN TAU ACCUMULATION AND MEMORY DECLINE
Structural Tract Alterations Predict Downstream Tau Accumulation in Amyloid-Positive Older Individuals
Jacobs HIL, Hedden T, Schultz AP, Sepulcre J, Perea RD, Amariglio RE, [et al.] Sperling RA, Johnson KA
Published in Nature Neuroscience on February 5, 2018

Alzheimer’s disease is characterized by the accumulation of amyloid and tau proteins in the brain. These proteins spread in specific patterns years before the first clinical symptoms become evident. Using longitudinal neuroimaging data, including novel methods to image tau pathology in 256 clinically normal older individuals, our team showed in humans that spreading of tau is more likely to occur via connectivity instead of proximity and that this spreading is driven by the amyloid protein. In addition, these events together were associated with memory decline. These findings suggest that amyloid is an important focus for disease-modifying drugs, but has to be targeted early to prevent spread of tau and the accompanying memory decline.

(Summary submitted by Heidi Jacobs, PhD, of the Department of Radiology)

4. ESTIMATING HEALTH OUTCOMES OF A LUNG CANCER SCREENING PROGRAM
Population Impact of Lung Cancer Screening in the United States: Projections From a Microsimulation Model
Criss SD, Sheehan DF, Palazzo L, Kong CY
Published in PLoS Medicine on February 7, 2018

Lung cancer is the leading cause of cancer death in the U.S. Screening with low-dose CT has been recommended by multiple medical societies for several years, though, the uptake of screening has been slow. We modeled the impact of lung cancer screening on the U.S. population and projected that 62,425 of lung cancer deaths could be avoided and 148,484 life-years could be saved if lung cancer screening was implemented from 2016 to 2030. Because of declining smoking prevalence in the U.S., the overall benefit of lung cancer screening would peak in 2021, providing a window of opportunity in the coming years for capturing significant benefit through screening.

(Summary submitted by Chung Yin Kong, PhD, and Steven Criss, BS, of the Institute for Technology Assessment)

5. LOOKING AT PLAQUE IN PATIENTS WITH ACUTE CORONARY SYNDROME
Nonculprit Plaque Characteristics in Patients With Acute Coronary Syndrome Caused by Plaque Erosion vs Plaque Rupture: A 3-Vessel Optical Coherence Tomography Study
Sugiyama T, Yamamoto E, Bryniarski K, Xing L, Lee H, Isobe M, Libby P, Jang IK
Published in JAMA Cardiology on February 7, 2018

There are two common mechanisms for acute heart attack and acute coronary syndromes: plaque rupture and plaque erosion. In current practice, patients with acute heart attack are uniformly treated with stent implantation irrespective of underlying pathology. This study demonstrates that plaque rupture, compared to plaque erosion, has very different biology. The level of panvascular instability/inflammation was significantly higher in plaque rupture compared to plaque erosion. Therapy focused on protection of endothelium or local flow disturbances rather than conventional cholesterol-lowering therapy should be considered in patients with plaque erosion.

(Summary submitted by Tomoyo Sugiyama, MD, PhD, of the Department of Medicine)

6. OSTEOPOROSIS DRUG COULD HELP MULTIPLE MYELOMA PATIENTS WHO HAVE BONE DISEASE
Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Double-Dummy, Randomised, Controlled, Phase 3 Study
Raje N, Terpos E, Willenbacher W, Shimizu K, García-Sanz R, Durie B, [et al.] Roodman GD
Published in The Lancet Oncology on February 8, 2018

Bone disease is a common problem for multiple myeloma (MM) patients and is a major source of morbidity resulting in skeletal issues such as pathological fractures or cord compression requiring surgery and/or radiation. To date, the only FDA-approved treatment for bone disease in MM has been Zoledronic trial. We have found a new alternative called denosumab, a monoclonal antibody targeting a critical factor in the pathogenesis of MM-related bone disease. Our study randomized 1,718 newly-diagnosed patients with at least one bone lesion to denosumab v. zoledronic acid. Our results establish the effectiveness and safety of denosumab, providing a new alternative to the treatment of MM-related bone disease.

(Summary submitted by Noopur Raje, MD, of the Cancer Center and Department of Medicine)

7. NEW TREATMENT FOR PERIPHERAL NERVOUS SYSTEM TUMORS WITHOUT RISK OF HEARING LOSS
Targeting the cMET Pathway Augments Radiation Response Without Adverse Effect on Hearing in NF2 Schwannoma Models
Zhao Y, Liu P, Zhang N, Chen J, Landegger LD, Wu L, [et al.] Jain RK, Xu L
Published in PNAS on February 9, 2018

Tumors associated with the genetic disorder neurofibromatosis 2 (NF2) may reduce hearing. The standard therapy for NF2 tumors is radiotherapy, which provides local control but can further reduce hearing. We report that the use of the anti-cancer drug crizotinib can enhance the efficacy of radiotherapy in mouse models of NF2, thus allowing a reduction in radiation dosage, and in vivo cytotoxicity against human NF2 cells. We also describe creation of a novel mouse model that mimics NF2-associated hearing loss and a better system for culturing tumor cells from NF2 patients.

(Summary submitted by Rakesh Jain, PhD, and Lei Xu, MD, PhD, both of the Department of Radiation Oncology)

8. PET IMAGING CAN TRACK BIOLOGICAL CHANGES ASSOCIATED WITH ALZHEIMER’S DISEASE
Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease
Quiroz YT, Sperling RA, Norton DJ, Baena A, Arboleda-Velasquez JF, Cosio D, [et al.] Johnson KA
Published in JAMA Neurology on February 12, 2018

In the largest study of its kind, we used neuroimaging methods (i.e. MRI and PET imaging) to study the association between markers of brain pathology and memory function in young individuals (28-45yo) who are genetically destined to develop Alzheimer’s disease in their mid- forties. We showed that these individuals have amyloid pathology in their brains 10-15 years before symptom onset, and have tau pathology in their brains an average of 6 years before clinical onset. These findings provide evidence of the potential utility of PET imaging in early detection and tracking of Alzheimer’s disease pathology. They also provide valuable information for ongoing and future prevention clinical trials.

(Summary submitted by Yakeel Quiroz, PhD, of the Department of Psychiatry)

9. REPORT ON BENEFITS AND HARMS OF E-CIGARETTES
Balancing the Benefits and Harms of Electronic Cigarettes: A National Academies of Science, Engineering, and Medicine Report
Rigotti NA
Published in Annals of Internal Medicine on February 13, 2018

This commentary discusses the controversy regarding electronic cigarettes (e-cigarettes) and suggests how physicians could discuss the products in clinical practice. The report summarizes what is known about the health risks and benefits of these devices and concludes that e-cigarettes are less harmful than continuing to smoke cigarettes, but little is yet known about their long-term effects on health. Physicians are encouraged to use existing FDA-approved smoking cessation medications as first-line treatment rather than e-cigarettes. Smokers who choose to use e-cigarettes should be advised to switch completely to e-cigarettes, avoiding dual use with cigarettes which has little evidence of benefit, and eventually taper off e-cigarettes too.

(Summary submitted by Nancy Rigotti, MD, of the Department of Medicine)

10. DIFFERENTIATING KRAS PROTEINS' ROLE IN CANCER
Differential Effector Engagement by Oncogenic KRAS
Yuan TL, Amzallag A, Bagni R, Yi M, Afghani S, Burgan W [et al.], Benes CH, McCormick F
Published in Cell Reports on February 13, 2018

KRAS proteins drive the development of many human cancers. The most commonly mutated, KRAS is implicated in 95% of pancreatic, 40% of colorectal and 30% of non-small cell lung cancers. KRAS drives a number of pro-tumorigenic programs but how these differ across cancers is not well understood. The diversity of KRAS signal driven dependencies was probed using siRNA combinations ablating signaling nodes downstream of KRAS. This work performed in collaboration with UCSF and the NCI RAS Initiative delineates dependencies across KRAS cancers, identifies effectors regulating different aspect of KRAS biology and drug combinations addressing different KRAS cancer subtypes.

(Summary submitted by Cyril Benes, PhD, of the Department of Medicine)

11. DIGITAL MONITORING MAY HELP IDENTIFY PATIENTS LIKELY TO BENEFIT FROM IMMUNE CHECKPOINT THERAPY
Molecular Signatures of Circulating Melanoma Cells for Monitoring Early Response to Immune Checkpoint Therapy
Hong X, Sullivan RJ, Kalinich M, Kwan TT, Giobbie-Hurder A, Pan S [et al.] Toner M, Isselbacher KJ, Maheswaran S, Haber DA
Published in PNAS on February 16, 2018

New therapies using antibodies against immune checkpoints are dramatically changing the way we treat patients with metastatic melanoma. However, only a third of melanoma patients experience long-term benefit from this therapy. We have developed a blood test that measures early tumor response and identifies patients who are most likely to benefit from immunotherapy. We used microfluidic enrichment from a simple blood test to develop a digital RNA signature that quantifies the presence of melanoma circulating tumor cells (CTCs). In a cohort of 49 melanoma patients, we saw a decrease in CTC Score within 7 weeks of treatment initiation, which is predictive of progression-free survival and overall survival. Our results suggest that this blood-based test could be used to monitor early response to immunotherapy.

(Summary submitted by Shyamala Maheswaran, MD, of the Department of Surgery and Cancer Center)

12. EARLY CONSULTATION WITH A DERMATOLOGIST CAN IMPROVE OUTCOMES IN PATIENTS WITH SUSPECTED CELLULITIS
Effect of Dermatology Consultation on Outcomes for Patients With Presumed Cellulitis: A Randomized Clinical Trial
Ko LN, Garza-Mayers AC, St John J, Strazzula L, Vedak P, Shah R, [et al.] Kroshinsky D
Published in JAMA Dermatology on February 16, 2018

Cellulitis is a common skin infection that has a high misdiagnosis rate, leading to unnecessary antibiotic use and health care costs. In this study, we sought to determine whether dermatologic consultation decreases duration of hospital stay or intravenous antibiotic treatment duration in patients with cellulitis. We enrolled adult patients hospitalized with presumed diagnosis of cellulitis and randomized them to receive either the standard of care (i.e. treatment by primary medicine team), or dermatology consultation. We found that early dermatologic consultation can improve outcomes in patients with suspected cellulitis by identifying alternate diagnoses, treating modifiable risk factors, and decreasing length of antibiotic treatment.

(Summary submitted by Lauren Ko, PhD, of the Department of Dermatology)

13. HOUSING PROBLEMS FOUND TO BE COMMON AT COMMUNITY HEALTH CENTERS
Prevalence of Housing Problems Among Community Health Center Patients
Baggett TP, Berkowitz SA, Fung V, Gaeta JM
Published in JAMA on February 20, 2018

Although U.S. federally-funded community health center (CHC) patients are often socioeconomically disadvantaged, the extent of their housing problems was previously unknown. We used data from a national survey to assess the prevalence and health-related correlates of housing problems among adult CHC patients and found that 44 percent reported problems ranging from homelessness to unstable housing. The proportion reporting current homelessness was about seven times higher than in the overall U.S. population. These findings suggest that we should consider screening all CHC patients for housing problems.

(Summary submitted by Travis Baggett, MD, of the Department of Medicine)

14. IMPROVING SHARED DECISION MAKING AMONG MINORITY POPULATIONS
Effectiveness of the DECIDE Interventions on Shared Decision Making and Perceived Quality of Care in Behavioral Health With Multicultural Patients: A Randomized Clinical Trial
Alegria M, Nakash O, Johnson K, Ault-Brutus A, Carson N, Fillbrunn M, [et al.] Shrout PE
Published in JAMA Psychiatry on February 21, 2018

We sought to test the effectiveness of DECIDE (decide the problem; explore the questions; closed or open-ended questions; identify the who, why, or how of the problem; direct questions to your health care professional; enjoy a shared solution) which aims to reduce disparities in behavioral health care by activating patients and encouraging providers to work as partners. Findings from our randomized clinical trial of DECIDE show improvements in shared decision making and patient-perceived quality of care among racial/ethnic minorities. Furthermore, we find the greatest improvements when patients and providers receive the recommended number of sessions (6 for providers and 3 for patients). We hope to conduct future research in implementing, disseminating, and adapting the DECIDE programs across behavioral health care settings.

(Summary submitted by Margarita Alegria, PhD, of the Department of Medicine)

15. IDENTIFICATION OF GENETIC DEFECT THAT MAY CAUSE RARE MOVEMENT DISORDER
Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly
Aneichyk T, Hendriks WT, Yadav R, Shin D, Gao D, Vaine CA, [et al.] Bragg C, Talkowski ME
Published in Cell on February 22, 2018

X-linked Dystonia-Parkinsonism (XDP) is a severe neurodegenerative disorder indigenous to the Philippines. All individuals with XDP inherit a cluster of variants on the X-chromosome, known as a haplotype, but none of these variants have known functions, so the cause of XDP has remained elusive. We combined assembly of the genome and gene expression patterns in neural cells reprogrammed from skin cells in XDP patients to discover that a large DNA insertion known as an SVA retrotransposon ‘jumped’ into the TAF1 gene on the XDP haplotype and caused a change to normal expression of the gene. When we ‘cut out’ this SVA with CRISPR, it corrects the defect in patient cells, suggesting development of targeted therapeutics could be promising.

(Summary submitted by Michael Talkowski, PhD, of the Department of Neurology)

16. EXPLANATION FOR INITIAL TAU AGGREGATION IN BRAIN
Tau Protein Liquid-Liquid Phase Separation Can Initiate Tau Aggregation
Wegmann S, Eftekharzadeh B, Tepper K, Zoltowska KM, Bennett RE, Dujardin S, [et al.] Hyman BT
Published in The EMBO Journal on February 22, 2018

In Alzheimer’s disease, and other tauopathies, the abnormal accumulation of tau protein aggregates in the brain leads to neuronal death and, ultimately, to cognitive decline. We identified a new mechanism that can explain the initial aggregation of tau in the brain. Tau protein can adopt a liquid droplet and hydrogel-like state, which enables the transition from normal soluble into abnormal aggregated tau. This biophysical process, termed “liquid-liquid phase separation”, also was suggested as the underlying mechanism in ALS, and thus may resemble an unifying mechanism in different neurodegenerative diseases with a potential for novel treatment approaches.

(Summary submitted by Susanne Wegmann, PhD, of the Department of Neurology)

17. EXPLORING THE IMPACT OF CHROMOSOME NUMBER ON HEART'S ABILITY TO REGENERATE
Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish
González-Rosa JM, Sharpe M, Field D, Soonpaa MH, Field LJ, Burns CE, Burns CG
Published in Developmental Cell on February 26, 2018

Zebrafish hearts robustly regenerate dead or amputated muscle through the expansion of uninjured cells, but the reasons remain a mystery. Our lab has pinpointed a fundamental difference between the non-regenerative hearts of humans and regenerative hearts of zebrafish. Whereas zebrafish cells contain two copies of every chromosome, human cells contain four. Using an innovative experimental technique, we induced zebrafish hearts to double their chromosome number. This caused the organ to respond to injury like the human heart by scarring instead of regenerating. These findings identify chromosome number as a critical determinant of heart regeneration and suggest that strategies for lowering the average chromosome number in the human heart may stimulate cardiac regeneration following heart attacks.

(Summary submitted by Juan Manuel Gonzalez-Rosa, PhD, of the Department of Medicine)

18. ALTERNATIVE IMAGING CONTRAST AGENTS
Chiral DOTA Chelators as an Improved Platform for Biomedical Imaging and Therapy Applications
Dai L, Jones CM, Chan WTK, Pham TA, Ling X, Gale EM, [et al.] Anderson CJ, Caravan P, Law GL
Published in Nature Communications on February 27, 2018

Gadolinium is a metal ion used to provide contrast in MRI scans. To be safe for human use, the gadolinium is tightly chelated to prevent it from being released into the body where it can cause toxic side effects. Recently, concerns have arisen regarding the long-term safety of gadolinium contrast agents. In a collaboration with Prof Ga-Lai Law at Hong Kong Polytechnic and Prof Carolyn Anderson at UPMC, our lab developed a platform technology of new gadolinium chelators that are much more stable than state of the art clinical compounds, and can be directed to specific organs.

(Summary submitted by Peter Caravan, PhD, of the Department of Radiology)

19. NEW MRI METHOD
Magnetic Resonance Mediated Radiofrequency Ablation
Hue YK, Guimaraes AR, Cohen O, Nevo E, Roth A, Ackerman JL
Published in the February issue of IEEE Transactions on Medical Imaging

We introduce magnetic resonance mediated radiofrequency ablation (MR-RFA), in which the MRI scanner uniquely serves both diagnostic and therapeutic roles. In MR-RFA, scanner-induced RF heating is channeled to the ablation site via a Larmor frequency RF pickup device and needle system, and controlled via the pulse sequence. When MR-RFA was performed on the livers of two healthy live pigs, resected livers exhibited clear thermal lesions. MR-RFA holds potential for integrating RF ablation tumor therapy with MRI scanning. MR-RFA may also add value to MRI with the addition of a potentially disposable ablation device, while retaining MRI’s ability to provide real time procedure guidance and measurement of tissue temperature, perfusion, and coagulation.

(Summary submitted by Jerome Ackerman, PhD, of the Department of Radiology)

Press Releases

A Circuitous Route to Inflammatory Bowel Disease
Featuring Ramnik Xavier, MD, PhD

Just because a gene is linked to a disease does not mean it plays a direct role, a point highlighted by one gene's connection to IBD.

Adding Crizotinib to Radiation Therapy May Help Preserve Hearing in Patients with NF2
Featuring Lei Xu, MD, PhD, Scott Plotkin, MD, PhD, Anat Stemmer-Rachamimov, MD, and Rakesh Jain, PhD

Adding the targeted cancer therapy drug crizotinib to radiation therapy for tumors associated with the genetic disorder neurofibromatosis 2 may reduce hearing damage that can be exacerbated by radiotherapy.

Cellular Models of Fetal Intestinal Tissue May Help Combat Deadly Neonatal Disease
Featuring Alessio Fasano, MD, and Stefania Senger, PhD

Cellular models of fetal and adult intestinal tissues generated by investigators from Mass General for Children have identified differences in the immune response to natural intestinal bacteria at different developmental ages.

Apalutamide Delays Progression of Nonmetastatic, Castration-Resistant Prostate Cancer
Featuring Matthew Smith, MD, PhD

A clinical trial led by investigators at Massachusetts General Hospital and the University of California, San Francisco found that treatment with an investigational androgen receptor inhibitor significantly delayed the development of metastasis in patients with prostate cancer that had become resistant to standard androgen-deprivation therapy.

Balancing the Benefits and Risks of Electronic Cigarettes
Featuring Nancy Rigotti, MD

What should physicians say to their patients who ask them about the safety of electronic cigarettes (e-cigarettes) and whether the devices can help them quit smoking? Massachusetts General Hospital physician Nancy Rigotti outlines what is and is not known about the risks and benefits of e-cigarettes in a commentary published in the February 13 issue of Annals of Internal Medicine.

Before-School Physical Activity Program Helps Improve Body Weight and Overall Wellness
Featuring Rachel Whooten, MD, and Elsie Taveras, MD, MPH

A Mass General for Children study finds that children participating in a 12-week, before-school physical activity program experienced improvement in body weight and social/emotional wellness, compared with their classmates who did not participate.

Cardiac Macrophages Found to Contribute to a Currently Untreatable Type of Heart Failure
Featuring Maarten Hulsmans, PhD, and Matthias Nahrendorf, MD, PhD

A team of Massachusetts General Hospital investigators has discovered, for the first time, that the immune cells called macrophages contribute to a type of heart failure for which there is no effective treatment.

Safe-Sleep Recommendations for Infants Have Not Reduced Sudden Deaths in Newborns
Featuring Ronald Kleinman, MD

An analysis by investigators from Mass General for Children and Newton-Wellesley Hospital of trends in sudden unexpected infant death over the past two decades finds that the drop in such deaths that took place following release of the 1992 American Academy of Pediatrics “back to sleep” recommendations did not occur in infants in the first month of life.

Expanding Hepatitis C Testing to All Adults is Cost-Effective and Improves Outcomes
Featuring Joshua Barocas, MD

According to a new study by researchers from Boston Medical Center, Massachusetts General Hospital and Stanford University, screening all adults for hepatitis C is a cost-effective way to improve clinical outcomes of HCV and identify more infected people, compared to current recommendations.

Housing Problems Found to be Common at Safety-Net Community Health Centers
Featuring Travis Baggett, MD, MPH

A new study by investigators at Massachusetts General Hospital, Boston Health Care for the Homeless Program and the University of North Carolina, Chapel Hill, finds that more than 40 percent of patients treated at U.S. community health centers have a history of housing problems.

Scientific Statement Reviews Current Knowledge, Best Practices for Spontaneous Coronary Artery Dissection
Featuring Malissa Wood, MD, and Mark Lindsay, MD

Many patients who experience a type of heart attack known as spontaneous coronary artery dissection (SCAD) may benefit most from a conservative approach to treatment, rather than more invasive procedures. A scientific statement reviewing current knowledge and best practices for SCAD treatment – put together by a collaborative working group from multiple institutions including Massachusetts General Hospital (MGH) – was published today in the American Heart Association (AHA) journal, Circulation.

Mass. General-Led Team Identifies Genetic Defect that May Cause Rare Movement Disorder
Featuring Michael Talkowski, PhD, and Cristopher Bragg, PhD

A Massachusetts General Hospital-led research team has found that a defect in transcription of the TAF1 gene may be the cause of X-linked dystonia parkinsonism, a rare and severe neurodegenerative disease.

Microfluidic Device Captures, Allows Analysis of Tumor-Specific Extracellular Vesicles
Featuring Shannon Stott, PhD

A new microfluidic device developed by investigators at Massachusetts General Hospital may help realize the potential of tumor-derived extracellular vesicles – tiny lipid particles that carry molecules through the bloodstream – as biomarkers that could monitor a tumor’s response to therapy and provide detailed information to guide treatment choice.

A Surprising Safety Benefit
Featuring Anupam Jena, MD

Thousands of firearm injuries occur in the United States each year, but the likelihood of such injuries appears to drop substantially when gun enthusiasts hold large national meetings, according to research led by Harvard Medical School. The results, published March 1 in The New England Journal of Medicine, show a 20 percent decline in gun injuries nationwide during the dates of the National Rifle Association’s annual convention.

Blog Posts

New Research Uncovers Gender Differences for Risk of Developing Heart Disease
Featuring Miriam A. Bredella, MD

What role does gender play in determining your risk for heart disease? New research from Mass General radiologist Miriam Bredella finds that women who have a certain type of body fat may have a greater risk for developing heart disease and other cardiovascular health issues than men.

A Link Between Flu and Heart Attacks? Mass General Cardiologist Weighs In
Featuring Malissa Wood, MD

New research has found yet another reason to avoid catching the flu this season - it could increase your risk of a heart attack. Malissa Wood, Co-Director of the Corrigan Women’s Heart Health Program at Massachusetts General Hospital, weighs in on these recent findings.

Understanding Why Exercise Works for Just About Everything
Featuring Gregory Lewis, MD

Why is exercise so good for your heart? Massachusetts General Hospital cardiologist and investigator Gregory Lewis explains the research that supports exercise's many health claims.

Surveys Show How Symptoms and Their Impacts Differ Among Adults with a Congenital Heart Defect
Featuring Ami B. Bhatt, MD, and Ada Stefanescu Schmidt, MD, MSc

When it comes to treating the symptoms of patients with a congenital heart defect, researchers from Massachusetts General Hospital are finding that a one-size-fits-all approach won’t meet all patients’ needs. The results of their recent survey provide insight into how clinicians can best tailor care for these patients.

Women’s Heart Health Program Leaders Look Ahead
Featuring Malissa Wood, MD, and Nandita Scott, MD

The Corrigan Women’s Heart Health Program at Massachusetts General Hospital focuses on awareness, treatments and research for the unique issues women face in maintaining heart health. Program co-directors Malissa Wood and Nandita Scott discuss what they've learned during its first decade and what still needs to be done.

Could Part of Our Genome Predict Future Risk for Heart Disease?
Featuring Saumya Das, MD, PhD

Research from Massachusetts General Hospital's Saumya Das is focused on a type of RNA called non-coding RNA which comprise a majority of the genome. Das is looking for RNA biomarkers in the blood that may forecast future risk of heart disease.

Could Strenuous Exercise Be Bad for Your Heart?
Featuring Aaron L Baggish, MD

Could strenuous exercise like running a marathon be bad for your heart? Recent research from Aaron Baggish, director of the Corrigan Minehan Heart Center Cardiovascular Performance Program at Massachusetts General Hospital, addresses this question.

Using Zebrafish Models to Study Cardiovascular Disease
Featuring Maryline Abrial, PhD

Meet Maryline Abrial, a postdoc in the Cardiovascular Research Center at Mass General. Abrial is studying zebrafish to gain insight that could one day benefit human patients with a genetic disorder called Marfan syndrome.

Remembering the Legacy of a Mass General Neurophysiologist and Pioneer in Race Relations at Harvard
Featuring S. Allen Counter

During Black History Month, we're honoring the legacy of S. Allen Counter. Counter, a Professor of Neurology at Harvard Medical School, a neurophysiologist at Massachusetts General Hospital and the founding director of the Harvard Foundation for Intercultural and Race Relations, is remembered for his contributions to research and his profound impact on inclusion and diversity at Harvard.

What’s Next for Cardiac Research and Clinical Care?
Featuring Malissa Wood, MD, Steven Lubitz, MD, MPH, and Aaron Baggish, MD

What do the new blood pressure guidelines mean for the field of cardiovascular research and clinical care? Hear from Massachusetts General Hospital investigators as they discuss this and other hot topics and what's next in the world of heart health.

Research Awards and Honors: February 2018
Featuring Dania Daye, MD, PhD, Leif Ellisen, MD, PhD, Srinivas Vinod Saladi, PhD, Shyamala Maheswaran, PhD, Raul Mostoslavsky, MD, PhD, and Sabrina Paganoni, MD, PhD

Please join us in congratulating all the Mass General researchers who received awards and honors this month!

Could Controlling Inflammation Improve Cystic Fibrosis Therapies?
Featuring Bryan Hurley, PhD

Bryan Hurley is exploring how controlling the inflammation associated with cystic fibrosis-related infections could be the key to developing improved therapies for patients.