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 April 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:

  • 19 new studies published in high impact journals, along with 16 summaries submitted by the research teams
  • 10 new research-related press releases from the Mass General Public Affairs office
  • 13 posts from the Mass General Research Institute blog

Publications List

*Author-submitted summaries available when indicated

ASSESSING USEFULNESS OF BLOOD CULTURES FOR IMAGING FOR CELLULITIS
Clinical Usefulness of Imaging and Blood Cultures in Cellulitis Evaluation
Ko LN, Garza-Mayers AC, St John J, Strazzula L, Vedak P, Dobry AS, Kroshinsky D
Published in JAMA Internal Medicine on April 2, 2018 | *Summary available

OVERVIEW OF ANALYSES ON TUMOR-CAUSING MOLECULAR PROCESSES
Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics
Ding L, Bailey MH, Porta-Pardo E, Thorsson V, Colaprico A, Bertrand D [et al], Getz G
Published in Cell on April 5, 2018

EXPLORING RESISTANCE TO GLIOMA TREATMENT
A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment
Griveau A, Seano G, Shelton SJ, Kupp R, Jahangiri A, Obernier K [et al], Jain RK, Rowitch DH
Published in Cancer Cell on April 6, 2018 | *Summary available | See press release

UNCOVERING MULTIPLE CAUSES OF FEINGOLD SYNDROME
Distinct Molecular Pathways Mediate Mycn and Myc-regulated miR-17-92 MicroRNA Action in Feingold Syndrome Mouse Models
Mirzamohammadi F, Kozlova A, Papaioannou G, Paltrinieri E, Ayturk UM, Kobayashi T
Published in Nature Communications on April 10, 2018 | *Summary available

UNDERSTANDING THE MOLECULAR BASIS OF BRAIN ORGANIZATION
Gene Expression Links Functional Networks Across Cortex and Striatum
Anderson KM, Krienen FM, Choi EY, Reinen JM, Yeo BTT, Holmes AJ
Published in Nature Communications on April 12, 2018 | *Summary available

DEVELOPMENT OF PROTOCOL FOR CRISPR GENOME EDITING EXPERIMENTS
Integrated Design, Execution, and Analysis of Arrayed and Pooled CRISPR Genome-editing Experiments
Canver MC, Haeussler M, Bauer DE, Orkin SH, Sanjana NE, Shalem O [et al], Pinello L
Published in Nature Protocols on April 12, 2018 | *Summary available

ACCESS TO MEDICAL EQUIPMENT FOR PEOPLE WITH DISABILITY
Accessibility of Medical Diagnostic Equipment — Implications for People with Disability
Iezzoni LI, Pendo E
Published in New England Journal of Medicine on April 12, 2018 | *Summary available

EVALUATING EFFICACY OF A TREATMENT FOR CASTRATION-RESISTANT 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 April 12, 2018

NEW STEP IN PERSONALIZED AND PRECISION MEDICINE FOR GLIOMA PATIENTS
Pharmacodynamics of Mutant-IDH1 Inhibitors in Glioma Patients Probed by In Vivo 3D MRS Imaging of 2-Hydroxyglutarate
Andronesi OC, Arrillaga-Romany IC, Ly KI, Bogner W, Ratai EM, Reitz K [et al], Batchelor TT
Published in Nature Communications on April 16, 2018 | *Summary available

IMPORTANCE OF REGULATORY T CELL ACTIVATION
Tumor Tolerance-Promoting Function of Regulatory T Cells Is Optimized by CD28, but Strictly Dependent on Calcineurin
Marangoni F, Zhang R, Mani V, Thelen M, Ali Akbar NJ, Warner RD [et al], Mempel TR
Published in Journal of Immunology on April 16, 2018 | *Summary available

3D MRI OF MICE BRAINS
Ex Vivo Mouse Brain Microscopy at 15T with Loop-gap RF Coil
Cohen O, Ackerman JL
Published in Magnetic Resonance Imaging on April 18, 2018 | *Summary available

ELIMINATING HIV-INFECTED MACROPHAGES
Resistance of HIV-infected Macrophages to CD8+ T Lymphocyte–mediated Killing Drives Activation of the Immune System
Clayton KL, Collins DR, Lengieza J, Ghebremichael M, Dotiwala F, Lieberman J, Walker BD
Published in Nature Immunology on April 19, 2018 | *Summary available

QUANTIFYING SOLID STRESS IN TUMORS
Quantifying Solid Stress and Elastic Energy from Excised or In Situ Tumors
Nia HT, Datta M, Seano G, Huang P, Munn LL, Jain RK
Published in Nature Protocols on April 19, 2018 | *Summary available

CELLULAR COMPOSITION OF AGGRESSIVE TYPE OF CHILDHOOD CANCER
Developmental and Oncogenic Programs in H3K27M Gliomas Dissected by Single-cell RNA-seq
Filbin MG, Tirosh I, Hovestadt V, Shaw ML, Escalante LE, Mathewson ND [et al], Regev A, Bernstein BE, Suvà ML
Published in Science on April 20, 2018 | *Summary available

ANALYSIS OF GENETIC VARIANTS THAT PROTECT AGAINST DISEASE
Analysis of Predicted Loss-of-function Variants in UK Biobank Identifies Variants Protective for Disease
Emdin CA, Khera AV, Chaffin M, Klarin D, Natarajan P, Aragam K [et al], Kathiresan S
Published in Nature Communications on April 24, 2018

IMPACT OF EXERCISE ON HEART HEALTH
Exercise Induces New Cardiomyocyte Generation in the Adult Mammalian Heart
Vujic A, Lerchenmüller C, Wu TD, Guillermier C, Rabolli CP, Gonzalez E [et al], Lee R, Rosenzweig A
Published in Nature Communications on April 25, 2018 | *Summary available | See press release

GENOME SEQUENCING AND AUTISM
An Analytical Framework for Whole-genome Sequence Association Studies and its Implications for Autism Spectrum Disorder
Werling DM, Brand H, An JY, Stone MR, Zhu L, Glessner JT [et al], Devlin B, Talkowski ME, Sanders SJ
Published in Nature Genetics on April 26, 2018 | *Summary available

NEW INSIGHTS INTO DEVELOPMENT OF DIFFUSE LARGE B CELL LYMPHOMA
Molecular Subtypes of Diffuse Large B Cell Lymphoma are Associated with Distinct Pathogenic Mechanisms and Outcomes
Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA [et al], Getz G, Shipp MA
Published in Nature Medicine on April 30, 2018 | *Summary available

A BINDING PROTEIN'S ROLE IN SKIN INTEGRITY
The RNA-binding Protein YBX1 Regulates Epidermal Progenitors at a Posttranscriptional Level
Kwon E, Todorova K, Wang J, Horos R, Lee KK, Neel VA [et al], Mandinova A
Published in Nature Communications on April 30, 2018 | *Summary available

Publication Summaries

1. ASSESSING USEFULNESS OF BLOOD CULTURES FOR IMAGING FOR CELLULITIS
Clinical Usefulness of Imaging and Blood Cultures in Cellulitis Evaluation
Ko LN, Garza-Mayers AC, St John J, Strazzula L, Vedak P, Dobry AS, Kroshinsky D
Published in JAMA Internal Medicine on April 2, 2018

Infectious disease society guidelines recommend against blood cultures and imaging for routine cases of cellulitis, a common skin infection. In this study, we quantified the extent, utility, and cost of imaging and blood cultures in the management of patients with cellulitis. We enrolled adult patients presenting to the emergency department with presumed diagnosis of cellulitis. As has been posited in previous literature, our results found that diagnostic imaging and blood cultures are currently overused in patients presenting with presumed cellulitis despite their lack of clinical utility. Additionally, we estimated the national annual cost of imaging and blood cultures for cellulitis patients at $226.9 million dollars.

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

2. EXPLORING RESISTANCE TO GLIOMA TREATMENT
A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment
Griveau A, Seano G, Shelton SJ, Kupp R, Jahangiri A, Obernier K [et al], Jain RK, Rowitch DH
Published in Cancer Cell on April 6, 2018

Malignant gliomas are aggressive brain tumors with poor prognosis despite surgical resection, radiation, and chemotherapy. Vascular endothelial growth factor (VEGF) plays an important role in tumor blood vessel formation and growth. Our team of collaborators has elucidated the role of the Olig2/Wnt pathway in mediating resistance to anti-VEGF therapy. We showed that Olig2/Wnt+ gliomas co-opt and migrate along pre-existing vessels as single cells, whereas Olig2/Wnt- gliomas form dense clusters around vessels. Wnt inhibition reduced tumor cell contact and migration along vessels. When combined with the chemotherapeutic agent temozolomide, Wnt inhibition significantly improved survival in mice bearing Olig2+ patient-derived glioma. These findings suggest that combination therapies targeting the Olig2/Wnt pathway may improve survival in patients.

(Summary submitted by Rakesh Jain, PhD, of the Department of Radiation Oncology)

3. UNCOVERING MULTIPLE CAUSES OF FEINGOLD SYNDROME
Distinct Molecular Pathways Mediate Mycn and Myc-regulated miR-17-92 MicroRNA Action in Feingold Syndrome Mouse Models
Mirzamohammadi F, Kozlova A, Papaioannou G, Paltrinieri E, Ayturk UM, Kobayashi T
Published in Nature Communications on April 10, 2018

Feingold syndrome (FS) is a rare genetic disorder characterized by skeletal abnormalities, among other symptoms. FS is caused by mutations in the MYCN gene (known as type 1 FS) or in miR-17-92 microRNAs (known as type 2 FS). It was previously thought that the two types of FS share a common pathological mechanism. Using mouse genetic models, we demonstrate that FS is primarily caused by deregulation of different signaling pathways between type 1 and 2 that regulate limb progenitor cell proliferation. Our results show that distinct mechanisms underlie type 1 and type 2 FS.

(Summary submitted by Tatsuya Kobayashi, MD, PhD, of the Endocrine Unit)

4. UNDERSTANDING THE MOLECULAR BASIS OF BRAIN ORGANIZATION
Gene Expression Links Functional Networks Across Cortex and Striatum
Anderson KM, Krienen FM, Choi EY, Reinen JM, Yeo BTT, Holmes AJ
Published in Nature Communications on April 12, 2018

The human brain is organized into a complex web of functional networks that link anatomically distinct regions. However, the biological mechanisms supporting the brain’s network organization remain unclear, particularly across cortical and subcortical territories with vastly divergent cellular and molecular properties. To understand the molecular basis of brain organization, we examined the association between cortico-striatal functional networks and gene expression in human postmortem brain tissue from the Allen Institute. Our study demonstrates correspondence of spatial patterns of gene expression to a limbic network, important for reward and affect, and a somato/motor network, involved in movement. In doing so, we discovered synchronized genetic signatures that recapitulate the spatial topography of distributed functional networks, nominating hundreds of potential molecular mechanisms supporting brain functions in health and disease.

(Summary submitted by Avram Holmes, PhD, formerly of the Martinos Center for Biomedical Imaging and Department of Psychiatry)

5. DEVELOPMENT OF PROTOCOL FOR CRISPR GENOME EDITING EXPERIMENTS
Integrated Design, Execution, and Analysis of Arrayed and Pooled CRISPR Genome-Eeiting Experiments
Canver MC, Haeussler M, Bauer DE, Orkin SH, Sanjana NE, Shalem O [et al], Pinello L
Published in Nature Protocols on April 12, 2018

CRISPR allows for efficient genome editing in cells. A variety of computational tools have been developed for the design and analysis of CRISPR genome editing experiments. However, oftentimes these tools are developed in isolation without features for facile integration with one another and/or without methods for wet-lab experimental implementation. Therefore, we developed a protocol to integrate robust, publicly available tools (CRISPOR, www.crispor.org and CRISPResso, http://crispresso.rocks/) for the design, execution, and analysis of CRISPR genome editing experiments for both small and large scale experiments. This protocol will allow other investigators to perform CRISPR experiments, from design to analysis, in a matter of weeks.

(Summary submitted by Luca Pinello, PhD, of the Molecular Pathology Unit and Cancer Center)

6. ACCESS TO MEDICAL EQUIPMENT FOR PEOPLE WITH DISABILITY
Accessibility of Medical Diagnostic Equipment — Implications for People with Disability
Iezzoni LI, Pendo E
Published in New England Journal of Medicine on April 12, 2018

People with disability can have trouble getting routine medical care because they cannot access examination tables, weight scales, x-ray machines, mammography equipment, and other medical equipment. In early January 2017, the federal government published standards on how to make medical equipment accessible to people with disability. The next step was for the U.S. Department of Justice (DOJ) to propose rules on which health care providers needed to install this accessible equipment. However, on December 26, 2017, the DOJ decided not to go forward with making these rules. People with disability may therefore continue to have trouble finding health care providers with equipment they can use.

(Summary submitted by Lisa Iezzoni, MD, of the Department of Medicine)

7. NEW STEP IN PERSONALIZED AND PRECISION MEDICINE FOR GLIOMA PATIENTS
Pharmacodynamics of Mutant-IDH1 Inhibitors in Glioma Patients Probed by In Vivo 3D MRS Imaging of 2-Hydroxyglutarate
Andronesi OC, Arrillaga-Romany IC, Ly KI, Bogner W, Ratai EM, Reitz K [et al], Batchelor TT
Published in Nature Communications on April 16, 2018

Molecular investigation of tumor biology has revealed the existence of a veritable cancer cycle that links genetic mutations, metabolic alterations and epigenetic modifications, which amplify and grow more complex with every turn of the cycle. Building on this emerging evidence, precision oncology uses molecular classification to select the right treatment at the right time for the right patient. Glioma brain tumors have frequent mutations in the gene encoding for isocitrate dehydrogenase enzyme which produces the oncometabolite D-2-hyroxyglutarate. Inhibitors of mutant isocitrate dehydrogenase enzyme have been developed to target this cancer pathway for the treatment of glioma. In this first-in-human study, by using the power of non-invasive imaging of D-2-hyroxyglutarate we were able to probe the effect of novel targeted therapy in glioma patients, accelerating the clinical translation and enabling precision oncology.

(Summary submitted by Ovidiu Andronesi, PhD, MD, of the Department of Radiology)

8. IMPORTANCE OF REGULATORY T CELL ACTIVATION
Tumor Tolerance-Promoting Function of Regulatory T Cells Is Optimized by CD28, but Strictly Dependent on Calcineurin
Marangoni F, Zhang R, Mani V, Thelen M, Ali Akbar NJ, Warner RD [et al], Mempel TR
Published in Journal of Immunology on April 16, 2018

Our immune system has the potential to eradicate cancer cells, but this is often prevented through the immune-suppressive activities of T regulatory cells (Treg). Here we define the relative importance of two molecules, calcineurin and CD28, for the ability of Treg within regional lymph nodes to “sense” the presence of a growing tumor. This event initiates changes in Treg that enable them to migrate to the tumor, and to locally shut off otherwise protective anti-tumor immune responses. Our results suggest that treatments that selectively interfere with Treg “sensing” of tumors through calcineurin and CD28 would unleash beneficial immune responses in cancer patients.

(Summary submitted by Francesco Marangoni, PhD, of the Department of Medicine)

9. 3D MRI OF MICE BRAINS
Ex Vivo Mouse Brain Microscopy at 15T with Loop-gap RF Coil
Cohen O, Ackerman JL
Published in Magnetic Resonance Imaging on April 18, 2018

Using a unique ultrahigh field MRI scanner built at Massachusetts General Hospital, fixed mouse brains were imaged in three dimensions, achieving some of the highest spatial resolutions ever reported for 3D volume MRI. A novel RF coil, a double loop-gap resonator, was designed and optimized to image these specimens. A spatial resolution of 47 × 47 × 47 μm3 (voxel volume 104 pL) in a 256 × 256 × 256 matrix was achieved in 1.8 hr, and 20 × 20 × 19 μm3 (voxel volume 7.6 pL) in a 620 × 620 × 640 matrix in 27 hr. To the authors’ knowledge, the latter represents the highest reported spatial resolution for 3D MRI scanning. MRI offers a rich range of endogenous image contrast in biological tissues compared to other imaging modalities. This work opens the possibility of 3D MRI of tissue specimens at unprecedented spatial resolution.

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

10. ELIMINATING HIV-INFECTED MACROPHAGES
Resistance of HIV-infected Macrophages to CD8+ T Lymphocyte–mediated Killing Drives Activation of the Immune System
Clayton KL, Collins DR, Lengieza J, Ghebremichael M, Dotiwala F, Lieberman J, Walker BD
Published in Nature Immunology on April 19, 2018

Despite the ability of anti-HIV drug therapy to control infection, there is still no cure for HIV and infected patients experience ongoing low-level virus replication, leading to chronic inflammation and contributing to increased risk of cardiovascular and other diseases. There is thus a critical need to eliminate residual HIV-infected cells and limit excessive inflammation, which are essential for achieving a cure. We have discovered that killer T cells have difficulty killing HIV-infected macrophages, leading to a prolonged macrophage-killer cell interaction. This interaction results in overstimulation of both the killer T cell and the macrophage and drives excessive inflammatory responses, which could contribute to chronic inflammation. Our work highlights the need to develop methods to more effectively eliminate infected, inflammation-promoting macrophages.

(Summary submitted by Bruce Walker, MD and Kiera Clayton, PhD, of the Ragon Institute of MGH, MIT, and Harvard)

11. QUANTIFYING SOLID STRESS IN TUMORS
Quantifying Solid Stress and Elastic Energy from Excised or In Situ Tumors
Nia HT, Datta M, Seano G, Huang P, Munn LL, Jain RK
Published in Nature Protocols on April 19, 2018

Explorations of the abnormal solid tumor microenvironment by Dr. Rakesh Jain and colleagues in the Edwin L. Steele Laboratories for Tumor Biology led to the discovery of a new mechanopathology called “solid stress,” an aberrant force exerted by the solid components of tumor tissue – cancer and stromal cells, and the extracellular matrix molecules they produce. In a new study, we outline in detail three distinct protocols to robustly and reliably map and quantify solid stress in tumors from humans or mouse models of cancer. Utilization of these techniques can potentially elucidate new targets in the tumor microenvironment to enhance drug delivery and efficacy, and, importantly, may establish solid stress as a predictive or prognostic factor in the clinic.

(Summary submitted by Rakesh Jain, PhD, and Meenal Datta, MS, of the Department of Radiation Oncology)

12. CELLULAR COMPOSITION OF AGGRESSIVE TYPE OF CHILDHOOD CANCER
Developmental and Oncogenic Programs in H3K27M Gliomas Dissected by Single-cell RNA-seq
Filbin MG, Tirosh I, Hovestadt V, Shaw ML, Escalante LE, Mathewson ND [et al], Regev A, Bernstein BE, Suvà ML
Published in Science on April 20, 2018

Our team from MGH and the Broad Institute used single-cell expression profiling to study a very aggressive pediatric brain tumor. The tumors arise exclusively in a specific location of the brain in young children, suggesting that a particular cell type –possibly undergoing rapid expansion at that age and location – is at the origin of these tumors. By sequencing the RNA from 3321 single cells from 6 tumors, we found that the tumors largely consist of cells that resemble oligodendrocyte precursor cells (OPC) and drive the growth of the tumor, whereas more differentiated cells were in the minority and lacked proliferative potential. We suggest that targeting the OPC marker PDGFRA or triggering cells to differentiate might allow therapeutic intervention in these as yet incurable malignancies.

(Summary submitted by Mario Suvà, MD, PhD, of the Department of Pathology)

13. IMPACT OF EXERCISE ON HEART HEALTH
Exercise Induces New Cardiomyocyte Generation in the Adult Mammalian Heart
Vujic A, Lerchenmüller C, Wu TD, Guillermier C, Rabolli CP, Gonzalez E [et al], Lee R, Rosenzweig A
Published in Nature Communications on April 25, 2018

The human heart has a relatively low capacity to regenerate itself. Young adults can renew around 1 percent of their heart muscle cells every year, and that rate decreases with age. Losing those cells is linked to heart failure, so interventions that increase cell formation have the potential to help prevent it. We found that 8 weeks of running exercise stimulated the heart to make new muscle cells in mice, both under normal conditions and after a heart attack. Our next step is to pinpoint which biological mechanisms link exercise with increased regenerative activity in the heart with the goal to better understand how these mechanisms could be manipulated therapeutically.

(Summary submitted by Carolin Lerchenmüller, MD, of the Department of Medicine)

14. GENOME SEQUENCING AND AUTISM
An Analytical Framework for Whole-genome Sequence Association Studies and its Implications for Autism Spectrum Disorder
Werling DM, Brand H, An JY, Stone MR, Zhu L, Glessner JT [et al], Devlin B, Talkowski ME, Sanders SJ
Published in Nature Genetics on April 26, 2018

We developed methods to analyze all three billion bases of the genome and simultaneously compare changes in the protein coding sequence, the noncoding regulatory sequence, and alterations to the structure of the genome in a single framework, which we call a category wide association study (CWAS). When we apply this CWAS to 2,076 genomes of individuals with autism and their family members, we find a very limited contribution of new mutations that arise outside of the protein coding sequence in autism. Without this framework, we would have incorrectly interpreted many different categories of mutations as being important in autism, emphasizing the importance of carefully considering the approach scientists take to interpret genome data in the emerging era of whole-genome sequencing and genomic medicine.

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

15. NEW INSIGHTS INTO DEVELOPMENT OF DIFFUSE LARGE B CELL LYMPHOMA
Molecular Subtypes of Diffuse Large B Cell Lymphoma are Associated with Distinct Pathogenic Mechanisms and Outcomes
Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA [et al], Getz G, Shipp MA
Published in Nature Medicine on April 30, 2018

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Although ~65% of DLBCL patients can be cured with standard therapy, the remainder require new treatment options. To discover new potential therapeutic targets, our team performed genomic analysis of 304 primary DLBCLs. We identified recurrent mutations, somatic copy-number alterations, and structural variants, that were integrated to define five distinct DLBCL subtypes. These subtypes were associated with different treatment outcomes, providing a new roadmap for more accurate DLBCL diagnosis. Moreover, characteristic somatic variants of the poorest-outcome subtypes can guide development of alternative therapeutic approaches.

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

16. A BINDING PROTEIN'S ROLE IN SKIN INTEGRITY
The RNA-binding Protein YBX1 Regulates Epidermal Progenitors at a Posttranscriptional Level
Kwon E, Todorova K, Wang J, Horos R, Lee KK, Neel VA [et al], Mandinova A
Published in Nature Communications on April 30, 2018

The function of the largest organ in the human body, the skin is dependent on the ability of skin stem cells to self-renew and regenerate its outermost layer, the epidermis. Although various mechanisms have been implicated in the control of skin stem cells function the precise nature of these processes is not yet understood. We have uncovered a novel pathway functioning as “guardian” of the skin stem cells, which protects them from senescence and preserves their ability to regenerate. We are offering insights into a new modality of stem cell control and currently unexplored opportunities for therapeutic interventions.

(Summary submitted by Anna Mandinova, PhD, MD, of the Department of Dermatology)

Press Releases

Combination Immunotherapy Improves Survival in Mouse Models of Mesothelioma
Featuring Mark Poznansky, MD, PhD, Jeffrey Gelfand, MD, and Huabiao Chen, PhD

Massachusetts General Hospital investigators have found that combined treatment with two cancer immunotherapy drugs significantly prolonged survival in mouse models of the aggressive cancer malignant mesothelioma.

Relaxation Response Therapy May Reduce Blood Pressure by Altering Expression of a Distinct Set of Genes
Featuring Randall Zusman, MD, Herbert Benson, MD, and John Denninger, MD, PhD

A study by investigators at Beth Israel Deaconess Medical Center, Massachusetts General Hospital, and the Benson-Henry Institute for Mind Body Medicine identified genes associated with the body’s response to relaxation techniques and sheds light on the molecular mechanisms by which these interventions may work to lower blood pressure.

Party Lines
Featuring Anupam Jena, MD

The divide that separates conservative and liberal values may be as wide now as it has ever been in our country. This divide shows itself in areas of everyday life, and health care is no exception. But do doctors’ political beliefs influence the way they practice medicine, choose therapies and treat patients?

RB1 Gene Mutations Underlie Clinical Resistance to CDK 4/6 Inhibitor Therapy for Breast Cancer
Featuring Aditya Bardia, MD, MPH

A multi-institutional research team led by a Massachusetts General Hospital investigator has identified what may be a novel mechanism underlying acquired resistance to CDK 4/6 inhibitor treatment for breast cancer.

Mass General-led Study May Reveal How Chronic Stress in Early Life Increases Vulnerability to PTSD
Featuring Ki Goosens, PhD

A collaboration between investigators at Massachusetts General Hospital and Khyber Medical University in Pakistan may have discovered how chronic stress experienced early in life increases vulnerability to post-traumatic stress disorder later in life.

Study Identifies Overdose Risk Factors in Youth with Substance Use Disorders
Featuring Amy Yule, MD, and Timothy Wilens, MD

A team of Massachusetts General Hospital investigators has identified factors that may increase the risk of drug overdose in adolescents and young adults.

Imaging May Allow Safe tPA Treatment of Patients with Unwitnessed Strokes
Featuring Lee Schwamm, MD, and Ona Wu, PhD

A study led by Massachusetts General Hospital investigators may lead to a significant expansion in the number of stroke patients who can safely be treated with intravenous tPA, the "clot busting" drug that has greatly reduced stroke-related disability and deaths in eligible patients.

Exercise May Help Make Heart Younger
Featuring Carolin Lerchenmüller, MD, and Anthony Rosenzweig, MD

In a new study in mice, researchers from Harvard University and Massachusetts General Hospital uncovered one reason why exercise is good for the heart: It stimulates the heart to make new muscle cells, both under normal conditions and after a heart attack.

Glioma Subtypes Determine How Dangerous Brain Tumors Spread, Evade Anti-Angiogenic Treatment
Featuring Rakesh Jain, PhD

A multi-institutional research team led by investigators from Massachusetts General Hospital and University of California San Francisco has identified a new mechanism by which the dangerous brain tumors called gliomas develop resistance to anti-angiogenic treatment.

State-of-the-art HIV Drug Could Curb HIV Transmission, Improve Survival in India
Featuring Amy Zheng and Kenneth A. Freedberg, MD, MSc

As study led by a Massachusetts General Hospital research team finds that an HIV treatment regimen widely used in North America and Europe would likely increase the life expectancy of people living with HIV in India and reduce the number of new HIV infections with minimal impact on the country’s HIV/AIDS budget.

Blog Posts

Game On for Autism Research at Mass General
Featuring Kirstin Birtwell, PhD

Researchers at the Lurie Center for Autism at Mass General for Children are exploring how commercial technologies might help children with autism communicate.

Updated Recommendations Provide Guidance for Women Experiencing Unwanted Hair Growth
Featuring Kathryn Martin, MD

For the first time since 2008, the Endocrine Society Task Force — which includes representatives from Massachusetts General Hospital — has issued an update to its Clinical Practice Guideline on hirsutism, a condition in which women experience unwanted hair growth.

Five Things to Know About Bone Marrow and Stem Cell Harvest
Featuring Jonathan Hoggatt, PhD

In a recent Cell study, Massachusetts General Hospital's Jonathan Hoggatt and a team of researchers describe an innovative new method for harvesting bone marrow stem cells for transplant. The process could be game changing for both the donor and the transplant recipient.

Breast Cancer Screening Research Highlights How Flawed Science Contributes to Health Disparities
Featuring David Chang, PhD, MBA, MPH

The current guidelines for breast cancer screening - which were based on data from primarily white women - recommend beginning mammograms at age 50. A new study from Massachusetts General Hospital published in JAMA Surgery finds that nonwhite women tend to get breast cancer in their 40s – a full two decades earlier than whites, and too soon to benefit from mammograms begun at age 50. These results highlight how flawed science can contribute to health disparities.

Research Team Develops Diagnostic Tool for Sepsis
Featuring Jouha Min, PhD

Researchers from the Mass General Center for Systems Biology (CSB) have developed a device that can rapidly diagnose sepsis, a potentially life-threatening complication of an infection. Learn more from Jouha Min, PhD, a postdoc in the CSB.

Survey Shows America’s Optimistic Yet Skeptical Attitudes Towards Science

A recent survey conducted by manufacturer 3M finds that most Americans find science fascinating and are generally optimistic about what it will bring, but there’s also a fair amount of science skepticism.

Mass General for Children Celebrates 10th Annual Research Day
Featuring Randy L. Buckner, PhD, Peter L. Slavin, MD, Ronald Kleinman, MD, and Allan Goldstein, MD, FACS

At the 10th anniversary of Mass General for Children (MGfC) Pediatric Research Day, speakers emphasized that the outlook for child health research – both in federal funding and at MGfC – is a bright one.

New Study from Mass General Seeks to Improve Shared Decision Making Among Minority Patients
Featuring Margarita Alegria, PhD

April is National Minority Health Month, a national effort designed to find ways to ensure that all patients have equal access to healthcare regardless of their race or ethnic background. Learn how a new study from Massachusetts General Hospital is providing insights into how to empower minority patients and improve their quality of care through a concept called shared decision making.

New Research Explores Link Between Mind-Body Techniques and Blood Pressure
Featuring Randall Zusman, MD, and John Denninger, MD, PhD

A new study from researchers at Massachusetts General Hospital, Benson-Henry Institute for Mind Body Medicine at Mass General, and Beth Israel Deaconess Medical Center has found a possible explanation for why performing mindfulness activities such as yoga and meditation can help patients reduce their high blood pressure without medication.

Genetic Insights, New Research Models Help to Drive New Rare Disease Research
Featuring Florian Eichler, MD

While it may not have been called rare disease research by name, Massachusetts General Hospital has been identifying and tracking rare diseases for more than a century, says Florian Eichler, MD, Director of the Center for Rare Neurological Diseases in the Department of Neurology. By combining new genetic insights with new models of collaborative research, Eichler and other clinician-investigators at Mass General are working to develop much needed new treatments for rare disease patients.

Mass General Participates in Week-long Celebration of Science and Discovery
Featuring Nitya Jain, PhD, and Giuseppina Romano-Clarke, MD

The Mass General Research Institute had a blast at this year's Cambridge Science Festival! We helped the next generation of scientists meet their microbes at the Science Carnival and Robot Zoo, and encouraged researchers to hone their science communication skills at our Science Slam.

Large-scale Study Provides New Insights into the Genetic Contributors to Schizophrenia
Featuring Tarjinder Singh, PhD

A key barrier to developing effective treatments for schizophrenia is the limited understanding of how the disorder develops. Learn how Tarjinder Singh, PhD, a postdoctoral fellow at Massachusetts General Hospital's Analytic and Translational Genetics Unit, is working to identify specific genetic differences that contribute to risk.

Awards and Honors: April 2018
Featuring Krishna Aragam, MD, MS, Michael Osborne, MD, Thaddeus Dryja, MD, Elena Hawryluk, MD, PhD, Sabrina Paganoni, MD, PhD, and Jason Roh, MD, MHS

Congratulations to the Mass General researchers who received awards and honors in April.