Snapshot of Science for April 2021

Welcome to our Snapshot of Science for April 2021

Here's a quick look at some recent publications, press releases and stories about the Mass General Research Institute community.

In this issue we highlight:

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

Publications

UNDERSTANDING SARS-COV-2 REPLICATION
SARS-CoV-2 Hijacks Folate and One-Carbon Metabolism for Viral Replication
Zhang Y, Guo R, Kim SH, Shah H, Zhang S, Liang JH, Fang Y, Gentili M, Leary CNO, Elledge SJ, Hung DT, Mootha VK, Gewurz BE
Published in Nature Communications on March 15, 2021 | *Summary available

USING BRAIN IMAGING TO PREDICT MIND WANDERING
Prediction of Stimulus-independent and Task-unrelated Thought from Functional Brain Networks
Kucyi A, Esterman M, Capella J, Green A, Uchida M [et al.], Whitfield-Gabrieli S
Published in Nature Communications on March 19, 2021 | *Summary available

SEX AND GENETICS IN PSYCHIATRIC DISORDERS
Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders
Blokland GAM, Grove J, Chen C, Cotsapas C, Tobet S [et al.], Goldstein, JM.
Published in Biological Psychiatry on March 22, 2021 | *Summary available

TECHNOLOGY DIFFERENCES IN GENOME SEQUENCING
Expectations and Blind Spots for Structural Variation Detection from Long-read Assemblies and Short-read Genome Sequencing Technologies
Zhao X, Collins RL, Lee WP, Weber AM, Jun Y [et al.], Talkowski ME
Published in American Journal of Human Genetics on March 26, 2021

PARENTAL SMOKING CESSATION VIA PEDIATRIC PRIMARY CARE
Cost-effectiveness of a Smoking Cessation Intervention for Parents in Pediatric Primary Care
Drouin O, Sato R, Drehmer JE, Nabi-Burza E, Hipple Walters B, Winickoff JP, Levy DE
Published in JAMA Network Open on April 01, 2021 | *Summary available

SEX AND AGE DIFFERENCES IN MILD TBI RECOVERY
Association of Sex and Age with Mild Traumatic Brain Injury-related Symptoms: A TRACK-TBI Study
Levin HS, Temkin NR, Barber J, Nelson LD, Robertson C [et al.], Zafonte R
Published in JAMA Network Open on April 01, 2021

COPING WITH YOUNG-ONSET DEMENTIA IN COUPLES
Thematic Analysis of Dyadic Coping in Couples with Young-Onset Dementia
Bannon SM, Grunberg VA, Reichman M, Popok PJ, Traeger L, Dickerson BC, Vranceanu AM
Published in JAMA Network Open on April 01, 2021 | *Summary available | Press Release

IMPROPER LABELING OF CANNABIS PRODUCTS
Variation in Cannabinoid Metabolites Present in the Urine of Adults Using Medical Cannabis Products in Massachusetts
Gilman JM, Schmitt WA, Wheeler G, Schuster RM, Klawitter J, Sempio C, Evins AE
Published in JAMA Network Open on April 01, 2021 | *Summary available | Press Release

PAIN THRESHOLDS DIFFER IN RED-HAIRED INDIVIDUALS
Reduced MC4R Signaling Alters Nociceptive Thresholds Associated with Red Hair
Robinson KC, Kemény LV, Fell GL, Hermann AL, Allouche J [et al.], Fisher DE
Published in Science Advances on April 02, 2021 | *Summary available | Press Release

GENE THERAPY TREATMENT FOR MLIV
MCOLN1 Gene Therapy Corrects Neurologic Dysfunction in the Mouse Model of Mucolipidosis IV
De Rosa S, Salani M, Smith S, Sangster M, Miller-Browne V [et al.], Grishchuk Y
Published in Human Molecular Genetics on April 05, 2021

NEW LUNG CANCER TREATMENT TECHNIQUE REDUCES ESOPHAGEAL DAMAGE
Assessment of a Contralateral Esophagus-sparing Technique in Locally Advanced Lung Cancer Treated with High-Dose Chemoradiation: A Phase 1 Nonrandomized Clinical Trial
Kamran SC, Yeap BY, Ulysse CA, Cronin C, Bowes CL [et al.], Willers H
Published in JAMA Oncology on April 08, 2021 | *Summary available | Press Release

SPLICING GENES TO REGULATE ENERGY PRODUCTION
Loss of LUC7L2 and U1 snRNP Subunits Shifts Energy Metabolism from Glycolysis to OXPHOS
Jourdain AA, Begg BE, Mick E, Shah H, Calvo SE [et al.], Mootha VK
Published in Molecular Cell on April 10, 2021 | *Summary available

GENES ON X CHROMOSOME LINKED TO CARDIOMETABOLIC RISK
Chromosome Xq23 is Associated with Lower Atherogenic Lipid Concentrations and Favorable Cardiometabolic Indices
Natarajan P, Pampana A, Graham SE, Ruotsalainen SE, Perry JA [et al.], Peloso GM
Published in Nature Communications on April 12, 2021 | *Summary available

ANTIBODIES IN HIV CONTROLLERS PAVE WAY FOR FUTURE VACCINE DESIGN
Distinct Clonal Evolution of B-cells in HIV Controllers with Neutralizing Antibody Breadth
Cizmeci D, Lofano G, Rossignol E, Dugast AS, Kim D [et al.], Juelg B
Published in eLife on April 12, 2021 | *Summary available

INCREASED UNDERSTANDING OF B-1 IMMUNE CELLS
B1a and B2 Cells Are Characterized by Distinct CpG Modification States at DNMT3A-maintained Enhancers
Mahajan VS, Mattoo H, Sun N, Viswanadham V, Yuen GJ [et al.], Pillai S
Published in Nature Communications on April 13, 2021 | *Summary available

OVERLAP BETWEEN MIGRAINE AND EPILEPSY
Spreading Depression as an Innate Antiseizure Mechanism
Tamim I, Chung DY, de Morais AL, Loonen ICM, Qin T [et al.], Ayata C
Published in Nature Communications on April 13, 2021 | *Summary available

PRENATAL MATERNAL STRESS LINKED TO OFFSPRING STRESS LATER IN LIFE
Impact of Prenatal Maternal Cytokine Exposure on Sex Differences in Brain Circuitry Regulating Stress in Offspring 45 Years Later
Goldstein JM, Cohen JE, Mareckova K, Holsen L, Whitfield-Gabrieli S [et al.], Hornig M
Published in Proceedings of the National Academy of Sciences of the United States of America on April 13, 2021 | *Summary available | Press Release

IMPACT OF TYPICAL AGING ON BRAIN PERFUSION
Characterizing Cerebral Hemodynamics Across the Adult Lifespan with Arterial Spin Labeling MRI Data from the Human Connectome Project-Aging
Juttukonda MR, Li B, Almaktoum R, Stephens KA, Yochim KM [et al.], Salat DH
Published in NeuroImage on April 15, 2021 | *Summary available

GENE-DIET INTERACTIONS FOR PRECISION NUTRITION
Genome-wide Gene-Diet Interaction Analysis in the UK Biobank Identifies Novel Effects on Hemoglobin A1c
Westerman KE, Miao J, Chasman DI, Florez JC, Chen H, Manning AK, Cole JB
Published in Human Molecular Genetics on April 16, 2021 | *Summary available

LONG TERM EFFECTS OF COVID IN YOUNG ATHLETES
SARS-CoV-2 Cardiac Involvement in Young Competitive Athletes
Moulson N, Petek BJ, Drezner JA, Harmon KG, Kliethermes SA [et al.], Baggish AL
Published in Circulation on April 17, 2021

LIVE IMAGING OF TAU FROM CELL FORMATION TO CELL DEATH
Continuous Monitoring of Tau-induced Neurotoxicity in Patient-derived iPSC-Neurons
Oakley DH, Klickstein N, Commins C, Chung M, Dujardin S [et al.], Frosch MP
Published in Journal of Neuroscience on April 20, 2021 | *Summary available

NEWLY DISCOVERED AIRWAY CELLS MAY SHED LIGHT ON SIDS AND OTHER CONDITIONS
Airway Basal Stem Cells Generate Distinct Subpopulations of PNECs
Mou H, Yang Y, Riehs MA, Barrios J, Shivaraju M [et al.], Ai X
Published in Cell Reports on April 20, 2021 | *Summary available | Press Release

STUDY PARTICIPATION BY SEX CAN AFFECT DOWNSTREAM GENETIC ANALYSES
Genetic Analyses Identify Widespread Sex-differential Participation Bias
Pirastu N, Cordioli M, Nandakumar P, Mignogna G, Abdellaoui A [et al.], Ganna A
Published in Nature Genetics on April 22, 2021 | *Summary available

IMPLICATIONS OF FDA APPROVAL OF SACITUZUMAB GOVITECAN
Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer
Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K [et al.], Rugo HS; ASCENT Clinical Trial Investigators
Published in New England Journal of Medicine on April 22, 2021 | *Summary available | Press Release

VAGUS NERVE STIMULATION AND UPPER LIMB REHABILITATION AFTER STROKE
Vagus Nerve Stimulation Paired with Rehabilitation for Upper Limb Motor Function after Ischaemic Stroke (VNS-REHAB): A Randomised, Blinded, Pivotal, Device Trial
Dawson J, Liu CY, Francisco GE, Cramer SC, Wolf SL [et al.], Kimberley TJ
Published in Lancet on April 24, 2021 | *Summary available

Publication Summaries

BLOCKING SARS-COV-2 REPLICATION
SARS-CoV-2 Hijacks Folate and One-Carbon Metabolism for Viral Replication
Zhang Y, Guo R, Kim SH, Shah H, Zhang S, Liang JH, Fang Y, Gentili M, Leary CNO, Elledge SJ, Hung DT, Mootha VK, Gewurz BE
Published in Nature Communications on March 15, 2021

When SARS-CoV-2 infects cells, it must make a huge number of copies of its RNA. Here, we used a technology called metabolomics to identify the earliest metabolic changes that accompany infection by this virus. We discovered that well before the host cell stops growing, there is a dramatic remodeling of host nucleotide metabolism. We find that the virus hijacks host one-carbon metabolism pathways and diverts them to support the production of their genomes. Several drugs, including the FDA approved drug methotrexate, blocks the early replication of this virus by targeting the host. While more studies are required, the work suggests that targeting host metabolic pathways may hold promise in preventing and even treating coronaviruses.

(Summary submitted by Vamsi Mootha, MD, Department of Medicine, Department of Molecular Biology, Center for Genomic Medicine)

People spend about 30%-50% of their daily lives engaged in "mind wandering," thinking about things that are completely unrelated to their immediate environment. This study shows that the degree to which someone is mind wandering can be predicted from a complex set of connections across the whole brain, identified in brain imaging data. The pattern shows greater expression in people with attention-deficit/hyperactivity disorder (ADHD) who frequently mind wander, providing neural evidence for "subtypes" of ADHD. In the future, new treatments for disorders of attention could be developed that focus on dialing down the expression of this mind wandering brain state.

(Summary submitted by Eve Valera, PhD, Martinos Center for Biomedical Imaging, Department of Psychiatry)

SEX AND GENETICS IN PSYCHIATRIC DISORDERS
Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders
Blokland GAM, Grove J, Chen C, Cotsapas C, Tobet S [et al.], Goldstein, JM
Published in Biological Psychiatry on March 22, 2021

In the largest genome-wide gene-by-sex analysis of mood and psychotic disorders to date, we found although there was substantial genetic overlap by sex, there were significant sex effects across disorders in several functional loci implicating neuronal development, immune and vascular pathways. Results demonstrated that the risk for these disorders is impacted by interactions of genotype with sex, beyond the impact of gonadal steroid hormones. The study underscores the importance of designing large-scale genetic studies to test for interactions with sex because the impact of sex, genes and pathophysiology will identify potential targets for sex-dependent or sex-specific therapeutic interventions.

(Summary submitted by Jill Goldstein, PhD, Innovation Center on Sex Differences in Medicine, Department of Psychiatry)

Our team completed a randomized trial establishing the effectiveness of the Clinical Effort Against Secondhand Smoke Exposure (CEASE) intervention for reducing parental smoking using a program of tobacco screening and treatment referral delivered through pediatric primary care. We calculated the incremental cost per quit of implementing the CEASE program in order to guide future program adoption by other pediatric practices. We found that the CEASE program cost from $762 to $1132 per additional parent who quit smoking, much less than many other health system-based tobacco cessation efforts. The CEASE program was inexpensive to initiate and maintain. Given the high burden of tobacco use, the program has the potential for substantial public health impact.

(Summary submitted by Douglas E Levy, PhD, Mongan Institute, Tobacco Research & Treatment Center, Department of Medicine)

COPING WITH YOUNG-ONSET DEMENTIA IN COUPLES
Thematic Analysis of Dyadic Coping in Couples With Young-Onset Dementia
Bannon SM, Grunberg VA, Reichman M, Popok PJ, Traeger L, Dickerson BC, Vranceanu AM
Published in JAMA Network Open on April 01, 2021 | Press Release

Young-onset dementias (YODs), defined by symptom onset before age 65, significantly disrupt couples' daily lives and challenges them to plan for an uncertain future with no available cure or meaningful treatments. Despite these significant challenges, there are no age-appropriate resources available for couples facing YOD to participate in together. This study is the first to use in-depth interviews to identify positive and negative coping patterns of couples living with a YOD diagnosis, which can inform the development of couples-based treatments for YOD. Findings underscore the importance of providing both partners with early training to manage their own difficult emotions and adopt a teamwork approach in order to collaboratively navigate challenges and plan for the future.

(Summary submitted by Sarah M. Bannon, PhD, Department of Psychiatry, Integrated Brain Health Clinical and Research Program)

IMPROPER LABELING OF CANNBIS PRODUCTS
Variation in Cannabinoid Metabolites Present in the Urine of Adults Using Medical Cannabis Products in Massachusetts
Gilman JM, Schmitt WA, Wheeler G, Schuster RM, Klawitter J, Sempio C, Evins AE
Published in JAMA Network Open on April 01, 2021 | Press Release

A growing market of medical cannabis products claim specific Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content, but regulation of THC and CBD content is inconsistent across states and generally weak. We quantified THC, CBD and their metabolites in urine of participants in a clinical trial of medical cannabis in Massachusetts. Among adults using medical cannabis, approximately one-third of samples from people reporting using CBD-dominant products contained no measurable CBD metabolite. Nearly one in five samples from those using vaped cannabis contained no detectable cannabinoids at all. This study indicates that adults using medical cannabis products may have incomplete or incorrect information regarding expected cannabinoid exposure from these purchased products.

(Summary submitted by Jodi Gilman. PhD, Department of Psychiatry, Center for Addiction Medicine)

Human data suggest that people with red hair/light-skin exhibit different pain thresholds than non-red-haired individuals. Here we utilized a mouse model with loss-of-function in the same melanocyte gene implicated in human redheads (MC1R) and indeed found a significant difference in pain thresholds. Mechanistic data utilized genetic (knockout/overexpression) and small molecule (agonist and antagonist) tools to identify the underlying mechanism. The red-haired background is associated with loss of both pro-pain and anti-pain peptides encoded by the POMC gene. However, the existence of multiple stable non-POMC opioid receptor ligands (eg enkephalin and dynorphin) effectively tipped the balance of endogenous peptides towards anti-pain signaling.

(Summary submitted by David Fisher, MD, PhD, Department of Dermatology, Cutaneous Biology Research Center)

NEW LUNG CANCER TREATMENT TECHNIQUE REDUCES ESOPHAGEAL DAMAGE
Assessment of a Contralateral Esophagus-Sparing Technique in Locally Advanced Lung Cancer Treated With High-Dose Chemoradiation: A Phase 1 Nonrandomized Clinical Trial
Kamran SC, Yeap BY, Ulysse CA, Cronin C, Bowes CL [et al.], Willers H
Published in JAMA Oncology on April 08, 2021 | Press Release

This pragmatic phase I trial tested a contralateral esophagus sparing technique in 25 patients with locally advanced lung cancer and treated with high-dose radiation and concurrent chemotherapy. The use of this technique with modern radiation resulted in reduced rates of severe esophagitis. These results support national guidelines and can be integrated into clinical practice.

(Summary submitted by Sophia Kamran, MD, Department of Radiation Oncology, Mass General Cancer Center)

Living organisms derive energy and building blocks from the nutrients they consume. Two main metabolic routes, glycolysis and OXPHOS, exist to achieve this task, and their use is accompanied with key tradeoffs. How cells of our organism shift between these two pathways is unknown. We identify that the splicing machinery, essential for the expression of genes but dysfunctional in human pathologies such as cancer, plays an unexpected role in this process by regulating some of the central genes in these metabolic routes. Our work sheds light on the regulation of energy metabolism and opens a metabolic perspective in our understanding of disorders characterized by mutation in splicing genes.

(Summary submitted by Vamsi K. Mootha, MD, Department of Medicine, Department of Molecular Biology, Center for Genomic Medicine)

The X chromosome is typically excluded from most genetic association studies due to technical challenges. We now use next-generation sequencing of the X chromosome to probe whether genetic variants on the X chromosome contribute to blood lipid concentrations and cardiometabolic risk. We found that variants at locus (Xq23) led to decreased atherogenic lipids, coronary artery disease risk and type 2 diabetes risk. The protective variants led to an increase in BMI, but also led to a preferential expansion of protective peripheral fat versus deleterious visceral fat. Bioinformatic analyses prioritized CHRDL1 as the responsible gene.

(Summary submitted by Pradeep Natarajan, MD, MMSc, Division of Cardiology, Department of Medicine, Cardiovascular Disease Prevention Center)

A small number of people living with HIV, called "HIV controllers," are able to naturally suppress the virus in their bodies. These unique individuals provide a great opportunity for researchers to elucidate how immune responses, such as neutralizing antibodies, can succeed against this infection. This study analyzed the HIV-specific antibody repertoire in 22 controllers from the Ragon Institute HIV controller cohort. We found that in individuals with particularly broad antibody responses that are able to neutralize different HIV strains, antibodies were highly mutated and consisted primarily of large clones. Understanding this antibody evolution will help pave the way for future vaccine design.

(Summary submitted by Boris Juelg, MD, PhD, Infectious Diseases Division, Department of Medicine)

This study provides new information about how we create a type of immune cell called a B-1 cell. B-1 cells make antibodies that clear a dangerous type of "bad" cholesterol and other unwanted waste from the blood and may thus prevent us from getting severe heart disease. This study also helps us understand how B-1 cells are kept from dividing in an uncontrolled manner and from becoming a type of leukemia called chronic lymphocytic leukemia or CLL. Our studies may help the development of new approaches to prevent severe heart disease and facilitate the prevention and treatment of certain leukemias.

(Summary submitted by Shiv Pillai, MD, PhD, Ragon Institute of MGH, MIT and Harvard, Mass General Cancer Center)

In this study, we discovered that spreading depression (SD) is a fundamental mechanism in the brain to terminate seizures. SD is an intense depolarization wave in the central nervous systems from insect to man and the electrophysiological basis of migraine aura. Here, we show that cerebral cortical or hippocampal seizures readily trigger SD, which, in turn, terminates the seizure, prevents seizure generalization, and reduces seizure recurrence with lasting effect. Therefore, SD acts as an "emergency brake" extinguishing the seizure. This previously unknown antiseizure effect provides a teleological explanation for the evolutionary persistence of SD and the clinical overlap between migraine and epilepsy.

(Summary submitted by Cenk Ayata, MD, Department of Neurology, Vascular Center)

In a unique cohort of men and women followed from the womb to early midlife, a recent brain imaging study showed that exposure during fetal development to inflammation-promoting cytokines, produced by mothers under negative stress, resulted in sex-associated differences in the offspring's brain in response to negative stress more than 45 years after birth. The study demonstrated that prenatal impact on the offspring's brain development may set the stage for producing a hypersensitivity to stressful exposures throughout life that differs by sex, underscoring that brain development begins before birth, is sex-dependent, and impacted by the mother's prenatal experience.

(Summary submitted by Jill Goldstein, PhD, Innovation Center on Sex Differences in Medicine, Department of Psychiatry)

IMPACT OF TYPICAL AGING ON BRAIN PERFUSION
Characterizing Cerebral Hemodynamics Across the Adult Lifespan with Arterial Spin Labeling MRI Data from the Human Connectome Project-aging
Juttukonda MR, Li B, Almaktoum R, Stephens KA, Yochim KM [et al.], Salat DH
Published in NeuroImage on April 15, 2021

Subtle decreases in brain perfusion over the human lifespan may contribute to tissue damage frequently observed in older adults and individuals with dementia. We used magnetic resonance imaging (MRI) to quantify age-effects on brain perfusion in a large cohort of typically aging adults between 36-90 years. We observed that brain perfusion decreases with increasing age, but the pattern of change may be different between gray and white matter. Furthermore, white matter regions known to be at elevated risk for age-related damage exhibited the lowest perfusion, indicating a potential link between vascular health and tissue damage associated with abnormal aging.

(Summary submitted by Meher R. Juttukonda, PhD, and David H. Salat, PhD, Martinos Center for Biomedical Imaging, Department of Radiology)

GENE-DIET INTERACTIONS FOR PRECISION NUTRITION
Genome-wide Gene-diet Interaction Analysis in the UK Biobank Identifies Novel Effects on Hemoglobin A1c
Westerman KE, Miao J, Chasman DI, Florez JC, Chen H, Manning AK, Cole JB
Published in Human Molecular Genetics on April 16, 2021

While diet is an important modifiable risk factor for type 2 diabetes, genetics may play a role in determining the optimal diet for each person. We performed gene-diet interaction analysis to understand how specific genetic variants modify the impact of dietary behaviors on hemoglobin A1c (HbA1c), a marker of diabetes status and risk. We found multiple genetic regions that modify the associations of both single dietary traits (such as bread or meat intake) and multi-factoral dietary patterns with HbA1c, and tested these interactions in individuals from different ancestries to understand their robustness. Our results highlight specific gene-diet interactions that could be relevant for precision nutrition while reinforcing the need for better dietary measurement strategies to enable further progress.

(Summary submitted by Kenneth Westerman, PhD, Department of Medicine, Clinical and Translational Epidemiology Unit)

LIVE IMAGING OF TAU FROM CELL FORMATION TO CELL DEATH
Continuous Monitoring of Tau-Induced Neurotoxicity in Patient-Derived iPSC-Neurons
Oakley DH, Klickstein N, Commins C, Chung M, Dujardin S [et al.], Frosch MP
Published in Journal of Neuroscience on April 20, 2021

Neuronal aggregation of the tau protein occurs in Alzheimer's disease (AD) and other neurodegenerative diseases.Tau aggregates are believed to spread from neuron-to-neuron via prion-like misfolded tau seeds. Our work develops a live-imaging system to visualize tau aggregation and tau-induced cell death in single human neurons derived from induced pluripotent stem cells. For the first time, we were able to longitudinally follow single human neurons from tau aggregate formation all the way to cell death. In addition, we find that human neurons carrying an AD-causing mutation in presenilin-1 undergo tau seeding more rapidly compared to controls. Finally, specific types of induced tau aggregates are found to be associated with increased neurotoxicity.

(Summary submitted by Derek H. Oakley, MD, PhD, Department of Pathology)

The human airway, which is responsible for breathing, contains only a few pulmonary neuroendocrine cells. These rare cells are believed to be one cell type. However, our recent study has found that these cells are much more variable and actually contain three different types. A new type is increased in cell number in the lung of infants who died of sudden infant death syndrome (SIDS). These findings support new ideas that pulmonary neuroendocrine cells may be involved in SIDS.

(Summary submitted by Xingbin Ai, PhD, Mass General for Children)

It has been common belief that genetic association studies are not affected by biases other than those due to population structure. However, with increasing numbers of individuals available, this has been disproven. To test this hypothesis, we looked for genetic differences between males and females outside the X chromosomes, finding 156 such spurious instances. We showed this is due to different characteristics of the volunteers between the two sexes, for example observing that participating females were more educated than males. We also demonstrate the potential consequences of such bias in downstream analyses, and stress the need to account for it.

(Summary submitted by Mattia Cordioli, University of Helsinki, Finland)

IMPLICATIONS FDA APPROVAL OF SACITUZUMAB GOVITECAN
Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer
Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K [et al.], Rugo HS; ASCENT Clinical Trial Investigators
Published in New England Journal of Medicine on April 22, 2021 | Press Release

Triple negative breast cancer (TNBC) represents an aggressive subtype of breast cancer. Sacituzumab govitecan is an antibody drug conjugate targeting Trop-2, an antigen overexpressed in majority of TNBC. In a global phase 3 randomized clinical trial (ASCENT), 529 patients with metastatic TNBC were randomized to sacituzumab govitecan or standard chemotherapy. Patients who received sacituzumab govitecan, as compared to standard chemotherapy, had better progression-free survival and overall survival. Based on results, the FDA granted full approval to sacituzumab govitecan, the first antibody-drug conjugate approved for patients with metastatic TNBC.

(Summary submitted by Aditya Bardia, MD, MPH, Division of Hematology/Oncology, Department of Medicine, Mass General Cancer Center)

Recovery from stroke is often incomplete, with many people left with impairment that prevents them from fully participating in their daily life. A multi-center, randomized, fully blinded, controlled trial examining the effects of vagus nerve stimulation paired with rehabilitation demonstrates that people made 2-3 times more gains in arm and function than people who received the same intense rehabilitation with sham stimulation. The findings suggest a potential new option to improve recovery in people with stroke.

(Teresa Jacobson Kimberley, PhD, PT, MGH Institute of Health Professions, MGH Center for Neurotechnology and Neurorecovery, Department of Neurology)

Press Releases

Potential New Treatment Strategy for Breast Cancer Cells That Have Spread to the Brain
Featuring Rakesh K. Jain, PhD

New research reveals that when breast cancer cells spread to the brain, they must boost production of fatty acids, the building blocks of fat, in order to survive there.

Sex Differences in the Brain in Response to Midlife Stress Linked to Fetal Stress Exposures
Featuring Jill M. Goldstein, PhD

Men and women whose mothers experienced stressful events during pregnancy regulate stress differently in the brain 45 years later, results of a long-term study demonstrate.

Thirteen New Alzheimer's Disease Genes Identified in First-of-its-kind Human Genome Study
Featuring Dmitry Prokopenko, PhD

In the first study to use whole genome sequencing to discover rare genomic variants associated with Alzheimer's disease (AD), researchers have identified 13 such variants (or mutations). In another novel finding, this study establishes new genetic links between AD and the function of synapses.

Research Reveals Why Redheads May Have Different Pain Thresholds
Featuring David E. Fisher, MD, PhD

New research led by investigators at Mass General provides insights on why people with red hair exhibit altered sensitivity to certain kinds of pain.

For 80% of Americans with Resolved Drug Problem, Significant Personal Achievements
Featuring John Kelly, PhD

Mass General's Recovery Research Institute has found that the majority of Americans who have resolved an alcohol or other drug problem report achievements related to self-improvement, family engagement, and civic and economic participation since resolving their addiction.

Scientists Uncover Mutations That Make Cancer Resistant to Therapies Targeting KRAS
Featuring Jessica J. Lin, MD

A gene called KRAS is one of the most commonly mutated genes in all human cancers, and targeted drugs that inhibit the protein expressed by mutated KRAS have shown promising results in clinical trials. Unfortunately, cancer cells often develop additional mutations that make them resistant to such targeted drugs. Now researchers have identified the first resistance mechanisms that may occur to these drugs and identified strategies to overcome them.

Vaccines and Functional Neurological Disorder: A Complex Story, Say Experts
Featuring David Perez, MD, MMSc

The COVID-19 vaccine may precipitate the development of functional neurological disorder, a neuropsychiatric disorder with symptoms such as limb weakness, gait problems, jerky movements, tremor and facial spasms.

Exercise Benefit in Breast Cancer Linked to Improved Immune Responses
Featuring Dai Fukumura, MD, PhD

Exercise training may slow tumor growth and improve outcomes for females with breast cancer—especially those treated with immunotherapy drugs—by stimulating naturally occurring immune mechanisms.

THC and CBD Content on Labels of Medicinal Cannabis Products May Not Be Accurate
Featuring Jodi M. Gilman, PhD

The contents of medical cannabis products can vary considerably from distributors' claims. This is particularly important when THC, the metabolite responsible for the "high" cannabis provides, is present in medical cannabis products labeled to be CBD only.

Study Reveals Cancer Immunotherapy Patients at Most Risk of Life-threatening Side Effects
Featuring Yevgeniy R. Semenov, MD, and Kerry Reynolds, MD

A new analysis led by researchers at Mass General indicates which cancer immunotherapy patients are at elevated risk of side effects severe enough to require hospitalization.

Study Reveals Crucial Details on Skin-related Side Effects of Cancer Immune Therapies
Featuring Yevgeniy R. Semenov, MD, and Kerry Reynolds, MD

A more comprehensive, population-level analysis now provides a thorough look at the extent of cancer immunotherapy side effects on the skin and provides insights on which patients may be more likely to experience them.

Diabetes Drug Shows Potential in Fighting Cancer
Featuring Bin Zheng, PhD

The anti-diabetic drug phenformin may prompt stronger cancer-fighting activities than its sister compound metformin, a finding that could have major implications for current and future clinical trials investigating both agents for their anti-cancer potential.

Couples and Young-onset Dementia: Study of Coping Offers Hope for New Interventions
Featuring Sarah Bannon, PhD

Researchers have used a couples-based framework to describe the experiences of individuals diagnosed with young-onset dementia (YOD) and their partners. This framework has been used to successfully develop patient-caregiver treatments for other severe medical conditions, including stroke, breast cancer and neurological injury.

Two Distinct Types of COVID-19-associated Acute Respiratory Distress Syndrome Identified
Featuring Lorenzo Berra, MD

Approximately one in four patients hospitalized for the acute respiratory distress syndrome (ARDS) associated with severe COVID-19 infections may have a distinct disease presentation or biochemical profile associated with organ dysfunction, blood-clotting abnormalities and greater risk of death than patients with other, seemingly similar forms of the disease.

Newly Discovered Airway Cells May Shed Light on SIDS and Other Conditions
Featuring Xingbin Ai, PhD

Recent research links certain cells that line the human airway with different infant diseases.

Novel Anti-cancer Agent Shows Promise in Treating the Most Aggressive Type of Breast Cancer
Featuring Aditya Bardia, MD, MPH

A unique antibody drug conjugate, which delivers a high dose of a cancer-killing drug to tumor cells through a targeted antibody, has been found in a global phase 3 clinical study to nearly double the survival time of patients with refractory metastatic triple-negative breast cancer.

Updated Advice for Safe COVID-19 Vaccination in People with High-risk Allergy Histories
Featuring Aleena Banerji, MD, and Kimberly Blumenthal, MD, MSc

At the end of 2020, experts led by allergists at Mass General examined all information related to possible allergic reactions to COVID-19 vaccinations. Now the team has published updated insights based on their experience overseeing more than 65,000 employees who have become fully vaccinated since that time.

Salad or Cheeseburger? Your Co-Workers Shape Your Food Choices
Featuring Douglas Levy, PhD

People in our social networks influence the food we eat—both healthy and unhealthy—according to a large study of hospital employees. The findings may guide efforts to improve population health.

Study Models Economic Impact of Proposed Law to Regulate High-risk Diagnostic Tests
Featuring Jochen Lennerz, MD, PhD

Legislation currently under consideration in U.S. Congress would increase regulatory oversight of certain diagnostic tests, and a new study by researchers at Mass General and colleagues from several other institutions demonstrates that its potential impact will depend on key details in the bill's final language.

Sculpting Radiation Beam Spares Lung Cancer Patients from Severe, Disabling Complication
Featuring Sophia C. Kamran, MD

A team of radiation oncologists at Mass General Cancer Center demonstrate in an early clinical trial that the radiation beam can be carefully "sculpted" to deliver the majority of a radiation dose directly to the tumor while effectively sparing tissues in the side of the esophagus away from the affected lung (the contralateral esophagus), thereby limiting inflammation and preserving swallowing function.

Childhood Psychiatric Symptom Risk Strongly Linked to Adverse Exposures During Gestation
Featuring Joshua L. Roffman, MD, MMSc

Harmful exposures during pregnancy, including some that occur even before pregnancy is recognized, appear to significantly increase a child's risk for psychiatric or behavioral problems early in life.

Use of E-cigarettes Plus Tobacco Cigarettes Linked to Higher Risk of Respiratory Symptoms
Featuring Sara Kalkhoran, MD, Krishna Reddy, MD, and Nancy Rigotti, MD

New research reveals that respiratory symptoms—such as cough and wheeze—are more likely to develop when people use both e-cigarettes and tobacco cigarettes together compared with using either one alone.

Blog Posts

Humans of MGRI: Katie Grant, BA

Katie Grant, BA, is the communications coordinator in the Mucosal Immunology and Biology Research Center, particularly for the Center for Celiac Research and Treatment.

Doctors and Hospitals Helped Nearly 50,000 to Vote in the 2020 Election Through Vot-ER
Featuring Alister Martin, MD, MPP and Aliya Bhatia, MPP

Vot-ER is a nonpartisan nonprofit that aims to promote health through voter registration. In the 2020 election, physicians and other healthcare providers helped nearly 50,000 patients and colleagues get ready to vote using Vot-ER.

COVID-19 Safety Measures are Still Crucial as Vaccination Rates Rise
Featuring Daniel Horn, MD

Daniel Horn, MD, shares what he has seen in the COVID-19 pandemic, what clinicians have learned over the past year and the importance of being vigilant as we move forward.

Rejection in Academia: A Door Open or a Door Closed?
Featuring James Quinn, PhD

James Quinn, PhD, a researcher in the Alzheimer's Clinical and Translational Research Unit, shares his experience with rejection and how it led to an outcome better than he imagined.

Conversations with Margarita: The Park Prescription
Featuring Margarita Alegría, PhD

In this month's "Conversations with Margarita," Margarita Alegría, PhD, shares the importance of equitable access to green spaces and the benefits it has on our health and happiness.

Celebration of Science Focuses on Lessons from COVID-19 and the Path Forward
Featuring

Can Mass General researchers use lessons from the COVID-19 pandemic to improve health care delivery and reduce disparities?

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Snapshot of Science for April 2021