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

Welcome to the May 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 16 summaries submitted by the research teams
  • 9 new research-related press releases from the Mass General Public Affairs office
  • 13 posts from the Mass General Research Institute blog

Publications

*Author-submitted summaries available when indicated

IDENTIFYING MUTATIONS DURING CELL DIVISION
Distinct Mutational Signatures Characterize Concurrent Loss of Polymerase Proofreading and Mismatch Repair
Haradhvala NJ, Kim J, Maruvka YE, Polak P, Rosebrock D, Livitz D [et al.], Getz G
Published in Nature Communications on May 1, 2018 | *Summary available


NEW INSIGHTS INTO HOW GENETICS INFLUENCE MIGRAINES
Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families
Gormley P, Kurki MI, Hiekkala ME, Veerapen K, Häppölä P [et al.], Palotie A
Published in Neuron on May 3, 2018 | *Summary available


COMPREHENSIVE VIEW OF FINLAND'S EVOLUTIONARY HISTORY
Haplotype Sharing Provides Insights into Fine-Scale Population History and Disease in Finland
Martin AR, Karczewski KJ, Kerminen S, Kurki MI, Sarin AP, Artomov M [et al.], Daly MJ
Published in American Journal of Human Genetics on May 3, 2018 | *Summary available


DIAGNOSIS OF BREAST CANCER DETECTED BETWEEN SCREENINGS
Breast Cancer With a Poor Prognosis Diagnosed after Screening Mammography with Negative Results
McCarthy AM, Barlow WE, Conant EF, Haas JS, Li CI, Sprague BL, Armstrong K
Published in JAMA Oncology on May 3, 2018 | *Summary available


NEW APPROACH FOR REGENERATING MUSCLE CELLS
Direct Reprogramming of Mouse Fibroblasts into Functional Skeletal Muscle Progenitors
Bar-Nur O, Gerli MFM, Di Stefano B, Almada AE, Galvin A, Coffey A [et al.], Hochedlinger K
Published in Stem Cell Reports on May 8, 2018 | *Summary available


GENE SPLICING AND RNAi DEFECTS
The Surveillance of Pre-mRNA Splicing is an Early Step in C. elegans RNAi of Endogenous Genes
Newman MA, Ji F, Fischer SEJ, Anselmo A, Sadreyev RI, Ruvkun G
Published in Genes & Development on May 8, 2018 | *Summary available


RISK FACTORS FOR POST-STROKE OUTCOMES
Diffuse Microvascular Dysfunction and Loss of White Matter Integrity Predict Poor Outcomes in Patients with Acute Ischemic Stroke
Rost NS, Cougo P, Lorenzano S, Li H, Cloonan L, Bouts MJ [et al.] Wu O
Published in Journal of Cerebral Blood Flow & Metabolism on May 8, 2018 | *Summary available


EXPANDING SCREENING FOR LYNCH SYNDROME
Universal Screening of Both Endometrial and Colon Cancers Increases the Detection of Lynch Syndrome
Adar T, Rodgers LH, Shannon KM, Yoshida M, Ma T, Mattia A [et al.], Chung DC
Published in Cancer on May 11, 2018 | *Summary available


TUMOR-SUPPRESSING AND -PROMOTING FUNCTIONS IN SQUAMOUS CELL CARCINOMA
Notch-effector CSL Promotes Squamous Cell Carcinoma by Repressing Histone Demethylase KDM6B
Al Labban D, Jo SH, Ostano P, Saglietti C, Bongiovanni M, Panizzon R, Dotto GP
Published in Journal of Clinical Investigation on May 14, 2018


NEW INSIGHTS INTO DEVELOPMENT OF HUMAN LANGUAGE
Neural Encoding and Production of Functional Morphemes in the Posterior Temporal Lobe
Lee DK, Fedorenko E, Simon MV, Curry WT, Nahed BV, Cahill DP, Williams ZM
Published in Nature Communications on May 14, 2018 | *Summary available


IDENTIFICATION OF MOLECULAR INHIBITOR THAT SUPPORTS SURVIVAL OF HIV-1-INFECTED CELLS
Anti-apoptotic Protein BIRC5 Maintains Survival of HIV-1-Infected CD4+ T Cells
Kuo HH, Ahmad R, Lee GQ, Gao C, Chen HR, Ouyang Z [et al], Lichterfeld M
Published in Immunity on May 15, 2018 | *Summary available


A NEW CONNECTION BETWEEN THE NERVOUS SYSTEM AND THE INTESTINAL EPITHELIUM
Intestinal Epithelial Wnt Signaling Mediates Acetylcholine-Triggered Host Defense against Infection
Labed SA, Wani KA, Jagadeesan S, Hakkim A, Najibi M, Irazoqui JE
Published in Immunity on May 15, 2018


IDENTIFYING GENETIC RISK FACTORS FOR A RARE AUTOIMMUNE DISEASE
A Whole-genome Sequence Study Identifies Genetic Risk Factors for Neuromyelitis Optica
Estrada K, Whelan CW, Zhao F, Bronson P, Handsaker RE, Sun C [et al.], Greenberg BM, MacArthur DG
Published in Nature Communications on May 16, 2018


A NEW WAY TO DIFFERENTIATE NEUROBLASTOMA
Targeted Inhibition of Histone H3K27 Demethylation is Effective in High-risk Neuroblastoma
Lochmann TL, Powell KM, Ham J, Floros KV, Heisey DAR, Kurupi RIJ [et al.], Benes CH, Faber AC
Published in Science Translational Medicine on May 16, 2018


DRUG USED TO TREAT MS SHOWS POTENTIAL FOR RARE NEURODEVELOPMENTAL DISEASE
Fingolimod Phosphate Inhibits Astrocyte Inflammatory Activity in Mucolipidosis IV
Weinstock L, Furness AM, Herron S, Smith SS, Sankar S, DeRosa SG [et al.], Slaugenhaupt S, Wood LB, Grishchuk Y
Published in Human Molecular Genetics on May 16, 2018 | *Summary available


NANOPARTICLES TARGETING TUMOR-ASSOCIATED MACROPHAGES
TLR7/8-agonist-loaded Nanoparticles Promote the Polarization of Tumour-associated Macrophages to Enhance Cancer Immunotherapy
Rodell CB, Arlauckas SP, Cuccarese MF, Garris CS, Li R, Ahmed MS [et al.], Weissleder R
Published in Nature Biomedical Engineering on May 21, 2018 | *Summary available


HIGHLIGHTING A KEY T CELL SUBSET THAT COULD LIMIT HIV REPLICATION
Frequencies of Circulating Th1-biased T Follicular Helper Cells in Acute HIV-1 Infection Correlate with the Development of HIV-specific Antibody Responses and Lower Set Point Viral Load
Baiyegunhi O, Ndlovu B, Ogunshola F, Ismail N, Walker BD, Ndung'u T, Ndhlovu ZM
Published in Journal of Virology on May 23, 2018 | *Summary available


USE OF HERPES VIRUS IN KILLING CANCER CELLS
Restriction of γ34.5-deleted Oncolytic Herpes Simplex Virus Replication in Glioblastoma Stem-Like Cells
Peters C, Paget M, Tshilenge KT, Saha D, Antoszczyk S, Baars A [et al.], Rabkin SD
Published in Journal of Virology on May 23, 2018 | *Summary available


COMBINING OPTICAL TECHNIQUES WITH ELECTRICAL RECORDINGS
Deep 2-photon Imaging and Artifact-Free Optogenetics Through Transparent Graphene Microelectrode Arrays
Thunemann M, Lu Y, Liu X, Kılıç K, Desjardins M, Vandenberghe M [et al.], Devor A, Kuzum D
Published in Nature Communications on May 23, 2018


IDENTIFYING CROHN’S DISEASE RISK FACTORS IN THE ASHKENAZI JEWISH POPULATION
Insights Into the Genetic Epidemiology of Crohn's and Rare Diseases in the Ashkenazi Jewish Population
Rivas MA, Avila BE, Koskela J, Huang H, Stevens C, Pirinen M [et al.], Cho JH, McGovern DPB, Daly MJ
Published in PLOS Genetics on May 24, 2018


RARE TRUNCATING MUTATIONS PLAY A ROLE IN NEURODEVELOPMENTAL DISEASE
Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum
Ganna A, Satterstrom FK, Zekavat SM, Das I, Kurki MI, Churchhouse C, [et al.], Neale BM
Published in American Journal of Human Genetics on May 31, 2018 | *Summary available


DISSECTING THE RNA COPYING PROCESS
Crystallographic Observation of Nonenzymatic RNA Primer Extension
Zhang W, Walton T, Li L, Szostak JW
Published in eLife on May 31, 2018 | *Summary available


Publication Summaries

1. IDENTIFYING MUTATIONS DURING CELL DIVISION
Distinct Mutational Signatures Characterize Concurrent Loss of Polymerase Proofreading and Mismatch Repair
Haradhvala NJ, Kim J, Maruvka YE, Polak P, Rosebrock D, Livitz D [et al.], Getz G
Published in Nature Communications on May 1, 2018

During cell division, mismatch repair (MMR) and polymerase proofreading identify and fix mistakes introduced in the replication of DNA to ensure that accurate copies of the genetic code are passed on. Impairment of either process contribute to cancer by accelerating the accumulation of mutations. In this study, our team reported that some tumors could unexpectedly withstand concurrent loss of both processes. A computational analysis identified distinct signatures of mutations, mostly observed in endometrial cancer, that are different from the signatures introduced by loss of either process alone or by their simple combination. This led to mechanistic insight into tumor evolution, suggesting a selective advantage to losing MMR following loss of polymerase proofreading, and may provide a potential biomarker for a subset of hypermutated tumors that have proven sensitive to immunotherapy.

(Summary submitted by Gad Getz, PhD, of the Department of Pathology)


2. NEW INSIGHTS INTO HOW GENETICS INFLUENCE MIGRAINES
Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families
Gormley P, Kurki MI, Hiekkala ME, Veerapen K, Häppölä P [et al.], Palotie A
Published in Neuron on May 3, 2018

Migraine tends to run in families, but it’s not clear if this clustering in families is due to rare, highly penetrant variants in individual genes or common ones with small effect sizes spread across many genes. Our team built a polygenic risk score using data from a migraine genome-wide association study, and used it to study the impacts of common and rare variation in a large cohort of families. We found a higher risk score in familial migraine cases, suggesting that common variants play a significant role in aggregation of migraine in families.

(Summary submitted by Aarno Palotie, PhD, MD, and Padhraig James Gormley, PhD, of the Department of Psychiatry)


3. COMPREHENSIVE VIEW OF FINLAND'S EVOLUTIONARY HISTORY
Haplotype Sharing Provides Insights into Fine-Scale Population History and Disease in Finland
Martin AR, Karczewski KJ, Kerminen S, Kurki MI, Sarin AP, Artomov M [et al.], Daly MJ
Published in American Journal of Human Genetics on May 3, 2018

Finland is a great place to infer population history and query disease genetics because it has a well-characterized history as a small founder population, unified medical records, and biobank-scale genetic data. Our international study assembled a comprehensive view of its evolutionary history by measuring segmental DNA sharing among pairs of Finns and individuals from neighboring countries that were inherited from common ancestors. We coupled this information with birth records to infer recent historical population dynamics, including population size changes, migration rates, and admixture events over time. We also traced the rise and spread of rare variants known to confer Finnish-specific disease risk that increased in frequency during the population bottleneck.

(Summary submitted by Alicia Martin, PhD, of the Department of Medicine)


4. DIAGNOSIS OF BREAST CANCER DETECTED BETWEEN SCREENINGS
Breast Cancer With a Poor Prognosis Diagnosed After Screening Mammography With Negative Results
McCarthy AM, Barlow WE, Conant EF, Haas JS, Li CI, Sprague BL, Armstrong K
Published in JAMA Oncology on May 3, 2018

Mammography reduces breast cancer mortality, but in some cases breast cancer is detected between screening exams after a negative mammogram - termed ‘interval cancer.’ We examined mammography outcomes for over 300,000 women and found that though the rate of interval cancer was small (5.9 per 10,000), these cancers tended to have poorer prognosis than screen detected cancers. Breast density increased risk of interval cancer, but breast density was not a good predictor of prognosis. Poor prognosis interval cancers were more likely to be diagnosed among women in their 40s compared to older women. We are currently looking for additional risk factors for poor prognosis interval cancers, so that high-risk women can take additional steps to prevent and detect breast cancer.

(Summary submitted by Anne Marie McCarthy, PhD, of the Department of Medicine)


5. NEW APPROACH FOR REGENERATING MUSCLE CELLS
Direct Reprogramming of Mouse Fibroblasts into Functional Skeletal Muscle Progenitors
Bar-Nur O, Gerli MFM, Di Stefano B, Almada AE, Galvin A, Coffey A [et al.], Hochedlinger K
Published in Stem Cell Reports on May 8, 2018

Our team has developed a simple and robust approach for directly reprogramming mature skin cells into immature muscle cells. By combining transient expression of a protein called MyoD and treatment with three small molecules, we converted mouse skin cells into induced myogenic progenitor cells (iMPCs). These cells propagated extensively and shared key molecular and functional properties with skeletal muscle stem cells. When transplanted into mice with leg injuries, the iMPCs engrafted in the damaged tissue and contributed to sustained muscle regeneration. This is the first direct conversion of skin cells into expandable, functional muscle progenitors. Our findings have potential relevance for the study and treatment of human muscle conditions such as muscular dystrophies for which there are currently no effective therapies.

(Summary submitted by Konrad Hochedlinger, PhD, of the Department of Stem Cell and Regenerative Biology)


6. GENE SPLICING AND RNAi DEFECTS
The Surveillance of Pre-mRNA Splicing is an Early Step in C. elegans RNAi of Endogenous Genes
Newman MA, Ji F, Fischer SEJ, Anselmo A, Sadreyev RI, Ruvkun G
Published in Genes & Development on May 8, 2018

Gene segments from viruses are detected as foreign and silenced by RNA interference (RNAi) pathways. Major targets of RNAi in nematodes have a small number of introns (segments of RNA that are removed during the production of proteins), are poorly conserved, and are less likely to be optimized. Consistent with intron surveillance by RNAi, a number of fungal and protist species that have lost their RNAi proteins in evolution show a correlated loss of particular intron splicing factors and intron numbers. We found that mutations in U1 and U2-snRNP-specific splicing factor genes cause defects in RNAi, and depletion of RNAi that target poorly conserved genes harboring few introns. Thus the RNAi pathway sees messenger RNAs (mRNAs) that are spliced less efficiently than normal.

(Summary submitted by Gary Ruvkun, PhD, of the Department of Genetics)


7. RISK FACTORS FOR POST-STROKE OUTCOMES
Diffuse Microvascular Dysfunction and Loss of White Matter Integrity Predict Poor Outcomes in Patients with Acute Ischemic Stroke
Rost NS, Cougo P, Lorenzano S, Li H, Cloonan L, Bouts MJ [et al.] Wu O
Published in Journal of Cerebral Blood Flow & Metabolism on May 8, 2018

We are currently limited in our ability to predict post-stroke outcomes, due in large part to the lack of knowledge with regard to risk factors that contribute to severity of stroke injury and the mechanisms of post-stroke recovery. In this paper, we studied these potential risk factors, namely the extent of small vessel dysfunction in brain MRIs of patients with acute ischemic stroke (AIS), in the form of blood–brain barrier (BBB) permeability and microstructural disarray of the white matter. We found that preserved integrity of the white matter tracts and of the BBB was linked to long-term functional outcomes in AIS patients. Furthermore, we identified an enzyme - matrix metalloproteinase-2 (MMP-2) – that serves as a biomarker of the underlying disease process. In future studies, these MRI markers may improve prediction of functional post-stroke outcomes.

(Summary submitted by Natalia Rost, MD, of the Department of Neurology)


8. EXPANDING SCREENING FOR LYNCH SYNDROME
Universal Screening of Both Endometrial and Colon Cancers Increases the Detection of Lynch Syndrome
Adar T, Rodgers LH, Shannon KM, Yoshida M, Ma T, Mattia A [et al.], Chung DC
Published in Cancer on May 11, 2018

Lynch syndrome is associated with a high risk of developing colon or endometrial cancer. Unfortunately, the syndrome is underrecognized in the population. Programs to screen all colon cancers for Lynch syndrome have been established, but we sought to define the added impact of screening all endometrial cancers as well. Working with our colleagues at North Shore Medical Center, we screened nearly 1800 colon and endometrial tumors and demonstrated that including endometrial tumors in the screening program increased the number of new patients diagnosed with Lynch syndrome by 50%. These previously unrecognized families can now benefit from interventions to reduce future cancer risk.

(Summary submitted by Daniel Chung, MD, of the Department of Medicine)


9. NEW INSIGHTS INTO DEVELOPMENT OF HUMAN LANGUAGE
Neural Encoding and Production of Functional Morphemes in the Posterior Temporal Lobe
Lee DK, Fedorenko E, Simon MV, Curry WT, Nahed BV, Cahill DP, Williams ZM
Published in Nature Communications on May 14, 2018

The study identifies a small area within the human posterior temporal lobe that is essential for the natural production of language. By using neural recording and stimulation techniques, we find that transient inhibition of this area impairs our ability to produce words with appropriate meaning but does not affect other linguistic processes such as comprehension or articulation. Detailed understanding of this brain area may help improve our ability to diagnose and treat disorders such as dyslexia, traumatic brain injury and stroke in which language production is often affected.

(Summary submitted by Ziv Williams, MD, of the Department of Neurosurgery)


10. IDENTIFICATION OF MOLECULAR INHIBITOR THAT SUPPORTS SURVIVAL OF HIV-1-INFECTED CELLS
Anti-apoptotic Protein BIRC5 Maintains Survival of HIV-1-Infected CD4+ T Cells
Kuo HH, Ahmad R, Lee GQ, Gao C, Chen HR, Ouyang Z [et al], Lichterfeld M
Published in Immunity on May 15, 2018

HIV can effectively infect and kill CD4 T cells, a specialized group of immune defense cells. But paradoxically, some HIV infected cells are able to stay alive long-term to keep an infection going. Our team reported that HIV turns on a cell survival program governed by a protein called BIRC5. We also found that compounds that interfere with BIRC5 could, in a lab dish, trigger death in infected T cells from HIV patients. These studies may allow to develop better strategies to eliminate residual reservoirs of HIV-1 infected cells that persist despite currently available antiretroviral therapy and represent the main barrier against a cure for HIV infection.

(Summary submitted by Mathias Lichterfeld, MD, PhD, of the Department of Medicine and Infectious Diseases)


11. DRUG USED TO TREAT MS SHOWS POTENTIAL FOR RARE NEURODEVELOPMENTAL DISEASE
Fingolimod Phosphate Inhibits Astrocyte Inflammatory Activity in Mucolipidosis IV
Weinstock L, Furness AM, Herron S, Smith SS, Sankar S, DeRosa SG [et al.], Slaugenhaupt S, Wood LB, Grishchuk Y
Published in Human Molecular Genetics on May 16, 2018

Mucolipidosis IV (MLIV) is an orphan neurodevelopmental disease that causes severe neurologic dysfunction and loss of vision with no cure. We investigated the effect of MLIV on inflammatory activation of a subtype of glial cells called astrocytes. In hopes to restore the normal function of the astrocytes, we dosed them with a clinically approved drug for multiple sclerosis, fingolimod. We found that the untreated MLIV astrocytes secrete a high number of pro-inflammatory compounds, but when treated with fingolimod, the pro-inflammatory signaling was reduced and overall cell function was recovered. These data suggest that fingolimod is a promising candidate for preclinical trail in our previously developed MLIV mouse model, which, in case of success, can be rapidly translated into clinical trial.

(Summary submitted by Amanda Furness, PhD, of the Department of Neurology)


12. NANOPARTICLES TARGETING TUMOR-ASSOCIATED MACROPHAGES
TLR7/8-agonist-loaded Nanoparticles Promote the Polarization of Tumour-associated Macrophages to Enhance Cancer Immunotherapy
Rodell CB, Arlauckas SP, Cuccarese MF, Garris CS, Li R, Ahmed MS [et al.], Weissleder R
Published in Nature Biomedical Engineering on May 21, 2018

Tumor-associated macrophages promote tumor growth, metastasis, and resistance to treatment by suppressing the body’s immune response. We report the development of a drug-loaded nanoparticle which targets these macrophages, converting them into a tumor-destructive cell type. The nanoparticle promoted anti-tumor immune response, controlling tumor growth in mice. When combined with immune checkpoint blockade (one of today’s most promising cancer therapies), the combination further improved response, eliminating tumors which are normally unaffected by checkpoint therapy alone.

(Summary submitted by Christopher Rodell, PhD, of the Department of Radiology)


13. HIGHLIGHTING A KEY T CELL SUBSET THAT COULD LIMIT HIV REPLICATION
Frequencies of Circulating Th1-biased T Follicular Helper Cells in Acute HIV-1 Infection Correlate with the Development of HIV-specific Antibody Responses and Lower Set Point Viral Load
Baiyegunhi O, Ndlovu B, Ogunshola F, Ismail N, Walker BD, Ndung'u T, Ndhlovu ZM
Published in Journal of Virology on May 23, 2018

Circulating T follicular helper (Tfh) cells are counterparts of Tfh cells found in lymph nodes and are divided into Tfh1, Tfh2, Tfh17 and Tfh1-17 subsets. We study found that a significant increase in the frequency of the Tfh1 subset during acute HIV infection had a strong significant association with slower disease progression mediated by anti-HIV antibody responses. These data suggest that this population provides the right instructive signals to B cells to generate effective anti-HIV antibodies. We concluded that the frequencies of Tfh1 cells could be used as a surrogate marker for effective antibody responses against HIV infection or vaccination.

(Summary submitted by Zaza M. Ndhlovu, PhD, of the Department of Medicine)


14. USE OF HERPES VIRUS IN KILLING CANCER CELLS
Restriction of γ34.5-deleted Oncolytic Herpes Simplex Virus Replication in Glioblastoma Stem-Like Cells
Peters C, Paget M, Tshilenge KT, Saha D, Antoszczyk S, Baars A [et al.], Rabkin SD
Published in Journal of Virology on May 23, 2018

Glioblastoma is a lethal brain tumor that resists current therapy. Oncolytic viruses, including oncolytic herpes simplex viruses (oHSVs), can replicate in and kill cancer cells. For safety purposes, oHSVs used to treat glioblastoma in the clinic lack a gene responsible for pathogenicity, known as the γ34.5 gene. We show that deletion of γ34.5 restricts oHSV growth in glioblastoma stem-like cells (GSCs), a subpopulation of cancer cells involved in tumor progression and resistance. In contrast, serum-cultured glioblastoma cells (ScGCs), representative of the bulk tumor and isolated from matched patients' tumor specimens, are permissive. This difference can be exploited to therapeutically target GSCs. Replication of γ34.5-deleted oHSV in GSCs can be restored by expression of Us11, enabling generation of more effective oHSVs.

(Summary submitted by Samuel Rabkin, PhD, of the Department of Neurosurgery)


15. RARE TRUNCATING MUTATIONS PLAY A ROLE IN NEURODEVELOPMENTAL DISEASE
Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum
Ganna A, Satterstrom FK, Zekavat SM, Das I, Kurki MI, Churchhouse C, [et al.], Neale BM
Published in American Journal of Human Genetics on May 31, 2018

The impact of rare DNA changes that impair gene function, aka “protein truncating variants” (PTVs), on common disease has been unclear. Our team led the largest exome sequencing project to date on more than 100,000 people, focusing on genes that are effectively broken by rare, and likely pathogenic, PTVs. We found that the variants raised risk for autism, schizophrenia, bipolar disorder, intellectual disability, ADHD and reduced height and they are associated with hospitalizations and overall mortality, suggesting a detrimental health impact that might be relevant for future applications in clinical genomics.

(Summary submitted by Andrea Ganna, PhD, of the Department of Medicine)


16. DISSECTING THE RNA COPYING PROCESS
Crystallographic Observation of Nonenzymatic RNA Primer Extension
Zhang W, Walton T, Li L, Szostak JW
Published in eLife on May 31, 2018

Modern cells use complex enzymes to replicate their DNA and copy DNA into RNA, and because of the importance of these enzymes they have been studied in great detail. X-ray crystallography has been particularly useful in allowing scientists to see, at an atomic level of detail, the various chemical steps in these central biological processes. In contrast, the chemical copying of RNA sequences without enzymes, which is thought to have been critical for the origin of life, is much less well understood. In this paper, we used x-ray crystallography to watch RNA molecules go through a series of chemical changes during the copying reaction, revealing for the first time an atomic level picture of this critical process.

(Summary submitted by Jack Szostak, PhD, of the Department of Genetics)

Press Releases

Artificial Intelligence Better Than Most Human Experts at Detecting Cause of Preemie Blindness
Featuring Jayashree Kalpathy-Cramer, PhD

An algorithm that uses artificial intelligence can automatically and more accurately diagnose a potentially devastating cause of childhood blindness than most expert physicians, suggests a study by investigators at Massachusetts General Hospital and Oregon Health & Science University.


Artificial Intelligence Detects Patterns of Gut Microbes that Indicate Cholera Risk
Featuring Regina C. LaRocque, MD, MPH

Researchers at Massachusetts General Hospital and Duke University used artificial intelligence to spot patterns within the communities of bacteria living in the human gut that could indicate who among the approximately one billion people around the globe at risk of cholera infection will get sick with the diarrheal disease.


Cellular Reprogramming Approach Promotes Muscle Regeneration in Injured Mice
Featuring Konrad Hochedlinger, PhD

Massachusetts General Hospital researchers have developed a simple and robust approach for directly reprogramming mature skin cells into immature muscle cells.


Neuroinflammation Seen in Spinal Cord, Nerve Roots of Patients with Chronic Sciatica
Featuring Yi Zhang, MD, PhD, and Marco Loggia, PhD

A study by Massachusetts General Hospital investigators has found, for the first time in humans, that patients with chronic sciatica – back pain that shoots down the leg – have evidence of inflammation in key areas of the nervous system.


Automated System Significantly Improves Identification of Patients at Risk for Ventilator-Associated Pneumonia
Featuring Brandon Westover, MD, PhD, and Erica Shenoy, MD, PhD

An automated system developed at Massachusetts General Hospital for identifying patients at risk for complications associated with the use of mechanical ventilators provided significantly more accurate results than did traditional surveillance methods, which rely on manual recording and interpretation of individual patient data.


MR Spectroscopy Imaging Reveals Effects of Targeted Treatment of Mutant IDH1 Gliomas
Featuring Ovidiu Andronesi, MD, PhD

Using a novel imaging method, a Massachusetts General Hospital research team is investigating the mechanisms behind a potential targeted treatment for a subtype of deadly brain tumors called gliomas.


Vascular Risk Factors Interact with Amyloid-beta Levels to Increase Age-related Cognitive Decline
Featuring Jennifer Rabin, PhD, Jasmeer Chhatwal, MD, PhD, and Reisa Sperling, MD

A Massachusetts General Hospital study finds that risk factors for heart disease and stroke appear to hasten the risk of cognitive decline in normal older individuals with evidence of very early Alzheimer’s-disease-associated changes in the brain.


Virtual Primary Care Visits for Follow-up Hypertension Care Have Outcomes Similar to Office Visits
Featuring Ronald Dixon, MD

A study conducted among patients at Massachusetts General Hospital and Brigham and Women’s Hospital found that virtual follow-up visits for patients with hypertension appeared just as effective as in-person office visits in helping maintain blood pressure control.


Screening Resident Physicians Entering Training Misses Many at Risk for Significant Sleep Impairment
Featuring Lori Berkowitz, MD, and Jonathan Zebrowski, MD

A Massachusetts General Hospital study finds that pre-existing sleep disorders are not the only risk factor for significant sleep impairment disorders in resident physicians.


Blog Posts

Study Looks at Risk Factors for Overdose in Adolescents
Featuring Amy Yule, MD

Researchers from the Addiction Recovery Management Service at Massachusetts General Hospital have identified factors that may increase the risk of drug overdose in adolescents and young adults. Here are five things to know about the study.


Mapping the Connections Between Allergies and the Microbiome
Featuring Nitya Jain, PhD

Nitya Jain, a researcher at the MassGeneral Hospital for Children's Mucosal Immunology and Biology Research Center, is studying how changes in the bacterial population in the gut influence T cell development and how signals between the two systems drive this process.


Racing to Stop a ‘Silent’ Killer
Featuring Cheng Wang, PhD

Despite advances in the early identification of some cancers, the ability to detect ovarian cancer in its early stages continues to elude researchers. Cheng Wang, PhD, a researcher and principal investigator in the Massachusetts General Hospital Vincent Center for Reproductive Biology, is determined to change that.


Mass General Investigators on the Cutting Edge of ALS Research
Featuring Merit Cudkowicz, MD, MSc, and Nazem Atassi, MD

While there is currently no cure for the neurodegenerative disease known as amyotrophic lateral sclerosis or ALS, researchers, including a team based at the Neurological Clinical Research Institute at Massachusetts General Hospital, are learning more in the hopes of identifying ways to slow or even one day reverse progression of the disease.


Research Finds Daily Exercise Can Make for Healthier, Younger Hearts
Featuring Anthony Rosenzweig, MD

Looking for another reason to stick to a regular exercise routine? New research from a team based at Massachusetts General Hospital, the Harvard Department of Stem Cell and Regenerative Biology, Harvard Medical School, and Harvard Stem Cell Institute shows that exercise can increase the generation of new heart cells, which might be crucial to maintaining heart function as we age.


Paganoni Advances ALS Research and Care with Technology
Featuring Sabrina Paganoni, MD, PhD

Sabrina Paganoni, a clinician and researcher in the Neurological Clinical Research Institute at Massachusetts General Hospital, has seen firsthand the potential power and impact technology could have for amyotrophic lateral sclerosis (ALS). Paganoni is using technology to find new treatments and improve the care and quality of life for patients with this progressive neurodegenerative disease with no known cure.


Online Platform Accelerates Rare Disease Research
Featuring Alex Sherman

In May, the Mass General Neurological Clinical Research Center NeuroBANK™ won Bio-IT World‘s Best Practice award in the Personalized & Translational Medicine category. What is the NeuroBANK, and how is it helping to accelerate the discovery, development, and delivery of future treatments for rare diseases such as ALS?


A Newly Discovered Link Between Gut Bacteria and Cholera
Featuring Regina C. LaRocque, MD, MPH, and Ana Weil, MD

Researchers from Massachusetts General Hospital, Duke University and the International Centre for Diarrheal Disease Research in Dhaka, Bangladesh have used machine learning algorithms to find patterns within communities of bacteria living in the human gut. These patterns could indicate who among the approximately one billion people at risk of cholera infection around the globe will get sick with the diarrheal disease.


Can Studying a Rare Inherited Form of ALS Lead to Earlier Diagnosis and New Treatments?
Featuring Katharine Nicholson, MD

Katharine Nicholson, a researcher in the Massachusetts General Hospital Neurological Clinical and Research Institute, is studying individuals with a rare hereditary form of ALS to gain a better understanding of the early stages of disease progression and help to develop new treatments.


How New Biomarkers and Smartphone Apps Could Provide New Hope for ALS Patients
Featuring James Berry, MD, MPH

How can smartphone apps improve ALS clinical trials? Learn how Mass General researcher James Berry is using technology and identifying new biomarkers with the goal of speeding up the process for identifying the next drug that will slow, reverse or even prevent ALS in the future.


Research Awards and Honors: May 2018
Featuring M. Amin Arnaout, MD, Jodie Babitt, MD, Murat Bastepe, MD, PhD, Florian Eichler, MD, Utibe Essien, MD, Mo Motamedi, PhD, and Stephanie Rutledge, MD

Congratulations to the Mass General researchers who received awards and honors this month!


New National Research Program Focuses on Connection and Community
Featuring Jordan Smoller, MD, ScD, Dean Xerras, MD, and Susan Edgman-Levitan, PA

Researchers from Massachusetts General Hospital have teamed up with the All of Us Research Program to build one of the world’s largest and most diverse data sets. The team hopes that engaging individuals from all walks of life will strengthen their national research efforts.


New Imaging Protocol Could Vastly Accelerate Clinical Trials for New ALS Treatments
Featuring Nazem Atassi, MD

Researchers at Massachusetts General Hospital have developed a new imaging protocol for ALS patients that could make it easier to test new treatments and identify early signs of the disease.