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 September 2017 edition of Snapshot of Science. Here's a quick look at some of the 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 14 summaries submitted by the research teams
  • 6 new research-related press releases from the Mass General Public Affairs office
  • 14 posts from the Mass General Research Institute blog

Publications List

*Author-submitted summaries available when indicated

CONVERSION OF NORMAL CELLS TO CANCER-ASSOCIATED CELLS
The ULK3 Kinase Is Critical for Convergent Control of Cancer-Associated Fibroblast Activation by CSL and GLI
Goruppi S, Procopio MG, Jo S, Clocchiatti A, Neel V, Dotto GP
Published in Cell Reports on September 5, 2017 | *Summary available

IDENTIFYING BLOOD AND KIDNEY CELL TYPES IN ZEBRAFISH
Dissecting Hematopoietic and Renal Cell Heterogeneity in Adult Zebrafish at Single-Cell Resolution Using RNA Sequencing
Tang Q, Iyer S, Lobbardi R, Moore JC, Chen H, Lareau C, [et al.] Langenau DMT.
Published in the Journal of Experimental Medicine on September 6, 2017
*Summary available

SORTING CIRCULATING TUMOR CELLS
Monolithic Chip for High-throughput Blood Cell Depletion to Sort Rare Circulating Tumor Cells
Fachin F, Spuhler P, Martel-Foley JM, Edd JF, Barber TA, Walsh J, [et al.] Toner M.
Published in Scientific Reports on September 7, 2017

AMPLIFYING THE RECRUITMENT OF INFECTION-CLEARING WHITE CELLS
Neutrophil-Derived Cytosolic PLA2α Contributes to Bacterial-Induced Neutrophil Transepithelial Migration
Yonker LM, Pazos MA, Lanter BB, Mou H, Chu KK, Eaton, AD, [et al.] Rajagopal J, Hurley BP.
Published in the Journal of Immunology on September 8, 2017 | *Summary available

PROTEIN INTERACTIONS AND ABNORMALITIES IN DIFFERENT CELL TYPES
Detection of Dysregulated Protein-Association Networks by High-Throughput Proteomics Predicts Cancer Vulnerabilities
Lapek JD Jr., Greninger P, Morris R, Amzallag A, Pruteanu-Malinici I, Benes CH, Haas W.
Published in Nature Biotechnology on September 11, 2017 | *Summary available

DETECTING CANCER GENES AND MUTATIONS
Analysis of Somatic Microsatellite Indels Identifies Driver Events in Human Tumors
Maruvka YE, Mouw KW, Karlic R, Parasuraman P, Kamburov A, Polak P, [et al.] Getz G.
Published in Nature Biotechnology on September 11, 2017 | *Summary available

PEDIATRIC INJURIES AND OFF ROAD VEHICLES
Age Legislation and Off-Road Vehicle Injuries in Children
Flaherty MR, Raybould T, Kelleher CM, Seethala R, Lee J, Kaafarani HMA, Masiaskos PT.
Published in Pediatrics (online before print) on September 11, 2017 | *See press release

GENETICS OF TYPE 2 DIABETES RISK
Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wde meta analysis
Wheeler E, Leong A, Liu CT, Hiver MF, Strawbridge RJ, Podmore C, Li M, [et al.], Meigs JB
Published in PLOS Medicine on September 12, 2017 | *See press release

TARGETING IMMUNE SYSTEM RESPONSES TO IMPROVE CANCER TREATMENTS 
Targeting CXCR4-Dependent Immunosuppressive Ly6Clow Monocytes Improves Antiangiogenic Therapy in Colorectal Cancer
Jung K, Heishi T, Incio J, Huang Y, Beech EY, Pinter M, [et al.], Jain RK, Fukumura D. 
Published in PNAS on September 12, 2017 | *Summary available

ABNORMALITIES IN VISUAL AND OLFACTORY SENSORY SYSTEMS AS BASIS FOR INTELLECTUAL IMPAIRMENT IN DOWN SYNDROME
Activity-Dependent Dysfunction in Visual and Olfactory Sensory Systems in Mouse Models of Down Syndrome
William CM, Saqran L, Stern MA, Chiang CL, Herrick S, Rangwala A, [et al.] Hyman BT.
Published in the Journal of Neuroscience on September 12, 2017

TRAUMATIC BRAIN INJURY AND NEUROIMMUNOLOGY
Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift
Jassam YN, Izzy S, Whalen M, McGavern DB, El Khoury J. 
Published in Neuron on September 13, 2017 | *Summary available

DEVELOPMENT OF TAU IN MOUSE AND HUMAN MODELS
Inhibition of p25/Cdk5 Attenuates Tauopathy in Mouse and iPSC Models of Frontotemporal Dementia
Seo J, Kritskiy O, Watson LA, Barker SJ, Dey D, Raja WK, [et al.] Dickerson BC, Haggarty SJ, Tsai, LH.
Published in Journal of Neuroscience on September 14, 2017 | *Summary available

EXAMINING ABNORMALITIES IN THE KIDNEY FILTRATION BARRIER
Ultrastructural Characterization of the Glomerulopathy in Alport Mice by Helium Ion Scanning Microscopy (HIM)
Tsuji, K., Suleiman, H., Miner, J.H., Daley, J.M., Capen, D.E., Păunescu, T.G., Lu, H.A.J.
Published in Scientific Reports on September 15, 2017 | *Summary available

USING CO2 LASERS TO TREAT TUMORS
Fractional Laser Exposure Induces Neutrophil Infiltration (N1 Phenotype) into the Tumor and Stimulates Systemic Anti-Tumor Immune Response
Kawakubo, M., Demehri, S., Manstein, D.
Published in PLoS One on September 18, 2017

LUNG CANCER MORTALITY AMONG PEOPLE LIVING WITH HIV WHO SMOKE 
Lung Cancer Mortality Associated With Smoking and Smoking Cessation Among People Living With HIV in the United States
Reddy KP, Kong CY, Hyle EP, Baggett TP, Huang M, Parker RA, [et al.] Walensky RP. 
Published in JAMA Internal Medicine on September 18, 2017 | *Summary available

FUNCTION OF AND INTERACTION BETWEEN RNA XIST AND X CHROMOSOMES
Repeat E Anchors Xist RNA to the Inactive X Chromosomal Compartment Through CDKN1A-Interacting Protein (CIZ1)
Sunwoo H, Colognori, D, Froberg JE, Jeon Y, Lee JT.
Published in PNAS on September 18, 2017 | *Summary available

REGULATION OF PROSTATE GROWTH
Androgenic to Estrogenic Switch in Human Adult Prostate Gland is Regulated by Epigenetic Silencing of Steroid 5α-reductase 2
Wang Z, Hu L, Salari K, Bechis S, Ge R, Wu S, [et al.] Olumi AF.
Published in the Journal of Pathology on September 20, 2017 | *Summary available

SNAP PARTICIPATION AND HEALTH CARE COSTS
Supplemental Nutrition Assistance Program (SNAP) Participating and Health Care Expenditures Among Low-Income Adults
Berkowitz SA, Seligman HK, Rigdon J, Meigs JB, Basu S.
Published in JAMA Internal Medicine on September 25, 2017 | *See press release

ANALYSIS OF HIV/AIDS TREATMENT TARGETS
The Clinical and Economic Impact of Attaining National HIV/AIDS Strategy Treatment Targets in the United States
Borre ED, Hyle EP, Paltiel AD, Neilan AM, Sax PE, Freedberg KA, Weinstein MC, Walensky RP
Published in the Journal of Infectious Diseases on September 28, 2017 | *See press release

Publication Summaries

1. CONVERSION OF NORMAL CELLS TO CANCER-ASSOCIATED CELLS
The ULK3 Kinase Is Critical for Convergent Control of Cancer-Associated Fibroblast Activation by CSL and GLI
Goruppi, S., Procopio, M.G., Jo, S., Clocchiatti, A., Neel, V., Dotto, G.P.
Published in Cell Reports on September 5, 2017

Cancer-associated fibroblasts (CAFs) are a subpopulation of cells that surround the tumor and encourage cancer evolution. Normal fibroblasts (NFs) are converted into CAFs by decreased levels of a DNA binding protein called CSL/RBPJ, which represses gene expression. Additionally, the signaling that activates the gene-regulating proteins called GLI (which is associated with promoting tumor growth) often malfunctions in CAFs. Our studies link CSL and GLI signaling in NF to CAF conversion. Loss of CSL leads to an increase of the expression of a gene known as ULK3, which in turn activates GLI signaling. Since we found that ULK3 expression is elevated in the CAFs of several tumors and that decreasing ULK3 levels abolishes the tumor enhancing properties of CAFs, ULK3 represents an attractive new tool to target CAFs in cancer therapy.

(Summary submitted by Sandro Goruppi, PhD, of the Cutaneous Biology Research Center)

2. IDENTIFYING BLOOD AND KIDNEY CELL TYPES IN ZEBRAFISH
Dissecting Hematopoietic and Renal Cell Heterogeneity in Adult Zebrafish at Single-Cell Resolution Using RNA Sequencing
Tang, Q., Iyer, S., Lobbardi, R., Moore, J.C., Chen, H., Lareau, C., [et al.] Langenau, D.M.
Published in the Journal of Experimental Medicine on September 6, 2017

Our lab constructed the first comprehensive molecular atlas of blood development and kidney cell functionality in adult zebrafish by using massively parallel single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow. This work uncovered novel blood and kidney cell types including two classes of natural killer cells, classically-defined and erythroid-primed blood stem cells, and kidney stem cells that have not been previously characterized at single-cell resolution in the zebrafish. This work provides a much needed resource for the community to identify novel/low-abundance cell types and to identify conserved gene programs that regulate blood and kidney cell function across species.

(Summary submitted by David Langenau, PhD, of the Molecular Pathology Unit)

3. AMPLIFYING THE RECRUITMENT OF INFECTION-CLEARING WHITE CELLS
Neutrophil-Derived Cytosolic PLA2α Contributes to Bacterial-Induced Neutrophil Transepithelial Migration
Yonker, L.M., Pazos, M.A., Lanter, B.B., Mou, H., Chu, K.K., Eaton, A.D., [et al.] Rajagopal, J., Hurley, B.P.
Published in the Journal of Immunology on September 8, 2017

Inflammatory white cells known as neutrophils leave the circulatory system and travel into tissue, ultimately breaking through the protective airway mucosa during bacterial infection. Signals from infected airway barriers initiate neutrophil recruitment to the airspace, while additional signals from newly arrived neutrophils potently amplify the recruitment process, thereby increasing the number of neutrophils fighting the infection within the airspace. Our team has identified a key enzyme expressed by neutrophils, critical for the synthesis of this amplification signal. The enzyme, called cytosolic phospholipase A2, represents a promising therapeutic target to control overly aggressive mucosal inflammation while preserving the important infection clearance capabilities of recruited neutrophils.

(Summary submitted by Bryan Hurley, PhD, of the Mucosal Immunology & Biology Research Center)

4. PROTEIN INTERACTIONS AND ABNORMALITIES IN DIFFERENT CELL TYPES
Detection of Dysregulated Protein-Association Networks by High-Throughput Proteomics Predicts Cancer Vulnerabilities
Lapek, J.D. Jr., Greninger, P., Morris, R., Amzallag, A., Pruteanu-Malinici, I., Benes, C.H., Haas, W.
Published in Nature Biotechnology on September 11, 2017

A comprehensive map of all protein-protein associations in mammalian cells (called the interactome) and how it varies across cell types and disease states will inform many aspect of cell biology and pathologies, such as cancer. We describe a new approach, called the ‘interactome mapping by high-throughput quantitative proteome analysis’ (IMAHP), that allows determination of protein-protein interactions much faster and at much lower cost that previous methods. In this approach, we measure very accurately the level of proteins across cell types and infer protein complexes through the co-regulation of protein levels. We further show that this can reveal anomalies in specific cells and point to vulnerabilities that can be exploited with anti-cancer drugs.

(Summary submitted by Cyril Benes, PhD, and Wilhelm Haas, PhD, both of the Cancer Center and Department of Medicine)

5. DETECTING CANCER GENES AND MUTATIONS
Analysis of Somatic Microsatellite Indels Identifies Driver Events in Human Tumors
Maruvka, Y.E., Mouw, K.W., Karlic, R., Parasuraman, P., Kamburov, A., Polak, P., [et al.] Getz, G.
Published in Nature Biotechnology on September 11, 2017

Microsatellites (MSs) are long stretches of short, repetitive DNA sequence, such as AGAGAGAGAG, that are common throughout the genome and are easily mutated when cells divide. However, their role in cancer is poorly understood due to challenges in identifying alterations in MSs from next-generation sequencing data. We recently developed new computational tools for identifying MS alterations from sequencing data, and identifying alterations in MSs that can drive cancer. By applying these tools across several thousands of samples representing dozens of tumor types, we identified unique properties of MS mutations and several novel cancer-associated genes.

(Summary submitted by Gad Getz, PhD, of the Cancer Center and Department of Pathology, and Yosef Maruvka, PhD, both of the Cancer Center )

6. TARGETING IMMUNE SYSTEM RESPONSES TO IMPROVE CANCER TREATMENTS
Targeting CXCR4-Dependent Immunosuppressive Ly6Clow Monocytes Improves Antiangiogenic Therapy in Colorectal Cancer
Jung, K., Heishi, T., Incio, J., Huang, Y., Beech, E.Y., Pinter, M., [et al.] Padera, T.P., Jain, R.K., Fukumura, D.
Published in PNAS on September 12, 2017

Limited survival benefit of antiangiogenic therapies that target blood vessels in tumors —such as Avastin (bevacizumab)—for colorectal cancer (CRC) patients is a major challenge for clinical oncology. We discovered that immune system responses that can help attack the cancer are being suppressed by certain antiangiogenic therapies. Furthermore, we identified the chemical mediators produced in response to antiangiogenic therapies that cause immunosuppressive cells to enter the tumor and limit anti-tumor action by the immune system. Using an FDA approved agent Plerixafor (AMD3100), we successfully targeted this pathway, prevented the infiltration of these immunosuppressive cells and improved the response of antiangiogenic treatment in our experimental models. This discovery has the potential for rapid clinical translation as it entails repurposing an FDA approved drug.

(Summary submitted by Dai Fukumura, MD, PhD, Rakesh Jain, PhD, Keehoon Jung, PhD, and Timothy Padera, PhD,, all of the Edwin L. Steele Laboratories)

7. GENETIC MARKERS AND RISK FOR ATRIAL FIBRILLATION
Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium
Weng, L.C., Lunetta, K.L., Müller-Nurasyid, M., Smith, A.V., Thériault, S., Weeke, P.E., [et al.] Lubitz, S.A.
Published in Scientific Reports on September 12, 2017

Both genetic mutations as well as risk factors such as age, male sex, hypertension, and obesity have been associated with an irregular and often rapid heart rate known as atrial fibrillation. Whether the risk conferred by genetic susceptibility varies according to the presence of clinical risk factors has remained unclear. We examined about 2.5 million genetic variants in nearly 8,000 individuals with atrial fibrillation and 80,000 without. We observed that variants of a specific gene involved in heart and lung development had a greater impact among those who developed atrial fibrillation at an early age rather than at older ages. Overall the findings suggest that while the biological mechanisms of atrial fibrillation may differ between older and younger individuals, in general, individual genetic variants confer a similar magnitude of impact on arrhythmia risk regardless of clinical risk factor status.

(Summary submitted by Steven Lubitz, MD, MPH, of the Cardiovascular Research Center)

8. GENE VARIANTS AND DIAGNOSIS OF TYPE 2 DIABETES
Impact of Common Genetic Determinants of Hemoglobin A1c on Type 2 Diabetes Risk and Diagnosis in Ancestrally Diverse Populations: A Transethnic Genome-Wide Meta-Analysis
Wheeler, E., Leong, A., Liu, C.T., Hivert, M.F., Strawbridge, R.J., Podmore, C., [et al.] Meigs, J.B.
Published in PLoS Medicine on September 12, 2017

Our large international genetics research team (named MAGIC – Meta Analysis of Glucose and Insulin Consortium) identified 60 gene variants – 42 for the first time – that influence blood levels of Hemoglobin A1c (A1C), used both to diagnose and manage diabetes. Together, 60 variants had modest influences on A1C in white Americans, but just one variant found only in African Americans (in the gene for the red blood cell enzyme G6PD) significantly reduced the accuracy of A1C testing in carriers, such that we estimate about 650,000 African Americans would be missed if screened for diabetes using HbA1c alone. This study has shown how new genetic information can inform public health efforts to reduce health disparities and control the current diabetes epidemic.

(Summary submitted by James Benjamin Meigs, MD, and Si Arn Aaron Leong, MD, MSc, both of the Division of General Internal Medicine)

9. TRAUMATIC BRAIN INJURY AND NEUROIMMUNOLOGY
Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift
Jassam, Y.N., Izzy, S., Whalen, M., McGavern, D.B., El Khoury, J.
Published in Neuron on September 13, 2017

Following a traumatic brain injury (TBI), extensive and lasting damage is sustained through a complex cascade of events referred to as “secondary injury.” Inflammation in the brain (neuroinflammation) is an important manipulatable aspect of secondary injury. Before developing therapies that regulate neuroinflammation in TBI, it is necessary to better understand the timing and complexity of this process. This paper presents our current understanding of the inflammatory response to TBI in a chronological and compartment-based manner, highlighting early changes in gene expression and initial signaling pathways that lead to neuroinflammation and linking the observed changes to the specific type of brain injury. Based on this, we propose a new paradigm to study neuroinflammation following TBI that takes into consideration the specific type of injury and the subsequent specific changes in the gene expression and protein profiles of neuroinflammatory cells associated with such injury.

(Summary submitted by Joseph El Khoury, MD, of the Center for Immunology and Inflammatory Diseases)

10. DEVELOPMENT OF TAU IN MOUSE AND HUMAN MODELS
Inhibition of p25/Cdk5 Attenuates Tauopathy in Mouse and iPSC Models of Frontotemporal Dementia
Seo, J., Kritskiy, O., Watson, L.A., Barker, S.J., Dey, D., Raja, W.K., [et al.] Dickerson, B.C., Haggarty, S.J., Tsai, L.H.
Published in Journal of Neuroscience on September 14, 2017

The abnormal activity of a multifunctional protein called tau encoded by the MAPT gene is increasingly recognized to be central to the development neurodegenerative disorders such as Alzheimer’s disease and other related dementias. In this study we used a mouse model with specific genetic mutations to elucidate the roles of a particular protein (p25) and a particular enzyme (CDK5) in the development of mutant tau-mediated dementia. To complement these mouse model studies, we also generated induced pluripotent stem cell models from a patient carrying a specific genetic tau mutation. Using genome editing, we were able to block abnormal production of p25 and CDK5 and development of tau. By advancing the development of innovative animal and human models for investigating the mechanisms of tauopathy, this work opens up new avenues for advancing precision medicine for neurodegeneration.

(Summary submitted by Stephen Haggarty, PhD, of the Center for Genomic Medicine, Chemical Neurobiology Laboratory, Departments of Neurology & Psychiatry)

11. EXAMINING ABNORMALITIES IN THE KIDNEY FILTRATION BARRIER
Ultrastructural Characterization of the Glomerulopathy in Alport Mice by Helium Ion Scanning Microscopy (HIM)
Tsuji, K., Suleiman, H., Miner, J.H., Daley, J.M., Capen, D.E., Păunescu, T.G., Lu, H.A.J.
Published in Scientific Reports on September 15, 2017

Leaking protein in urine, known as proteinuria, is a condition that is frequently seen in patients with diabetic nephropathy and many other kidney diseases. Appearance of proteinuria indicates damage of the filtration barrier of the kidney, but how disruption of kidney filtration barrier occurs has not been understood. Using a novel and powerful scanning microscopy technology known as helium ion scanning microscopy (HIM), we examined the kidney filtration structure in mice with proteinuria and found unprecedented details of the abnormalities in the kidney’s filtration barrier. Our data provides new information of ultrastructural features of the filtration barrier in association with their underlying molecular composition. This is a critical step to understand the pathological process of proteinuric kidney diseases.

(Summary submitted by Jenny (Hua) Lu, MD, PhD, of the Center for Systems Biology, Program in Membrane Biology, Division of Nephrology, and Department of Medicine)

 12. LUNG CANCER MORTALITY AMONG PEOPLE LIVING WITH HIV WHO SMOKE
Lung Cancer Mortality Associated With Smoking and Smoking Cessation Among People Living With HIV in the United States
Reddy, K.P., Kong, C.Y., Hyle, E.P., Baggett, T.P., Huang, M., Parker, R.A., [et al.] Walensky, R.P.
Published in JAMA Internal Medicine on September 18, 2017

Over 40 percent of people with HIV in the US smoke cigarettes. HIV itself increases the risk of lung cancer. We used a computer model to estimate the risk of dying from lung cancer among people with HIV, according to whether they smoke. We found that those who take antiviral medicines but smoke are approximately 10 times more likely to die from lung cancer than from HIV/AIDS. We projected that nearly 10 percent of all people in HIV care in the US will die from lung cancer if smoking patterns do not change. Smoking cessation should be a priority in HIV care.

(Summary submitted by Rochelle Walensky, MD, MPH, chief of the Division of Infectious Diseases, and co-director of the Medical Practice Evaluation Center, and Krishna Reddy, MD, of the Division of Pulmonary and Critical Care Medicine and the Medical Practice Evaluation Center)

13. FUNCTION OF AND INTERACTION BETWEEN RNA XIST AND X CHROMOSOMES
Repeat E Anchors Xist RNA to the Inactive X Chromosomal Compartment Through CDKN1A-Interacting Protein (CIZ1)
Sunwoo, H., Colognori, D., Froberg, J.E., Jeon, Y., Lee, J.T.
Published in PNAS on September 18, 2017

X-chromosome inactivation (XCI) is a key developmental process in sex-linked gene expression. Without XCI, female embryos die during development. When XCI is lost in cells in the body, there is increased risk of cancer — especially in blood cells. It is known that XCI depends critically on a long noncoding "Xist RNA.” This RNA coats the X-chromosome to be inactivated in females and recruits repressive factors to that chromosome. A major unanswered question in this process is how Xist “spreads” along the X-chromosome. We found a required interaction between a novel protein known as CIZ1 and Xist RNA. Without this interaction, the RNA cannot attach to the X-chromosome and instead of beginning the process of inactivation, the RNA detaches and floats away from the X. This new mechanistic finding advances understanding of how RNA controls gene expression and how loss of RNA-directed silencing can cause diseases such as cancer.

(Summary submitted by Jeannie Lee, MD, PhD, of the Department of Molecular Biology)

14. REGULATION OF PROSTATE GROWTH
Androgenic to Estrogenic Switch in Human Adult Prostate Gland is Regulated by Epigenetic Silencing of Steroid 5α-reductase 2
Wang Z, Hu L, Salari K, Bechis S, Ge R, Wu S, [et al.] Olumi AF.
Published in the Journal of Pathology on September 20, 2017

The prostate is the only solid organ that grows continuously throughout adulthood. While all men experience some prostate growth as they age, the rate of growth varies significantly among different men. The steroid 5α reductase type 2 (SRD5A2) enzyme is necessary for prostate development and growth. Contrary to common belief, in this study we demonstrate that 30% of adult human prostatic tissues do not express SRD5A2 and somatic suppression is dependent on epigenetic changes in the promoter region of the SRD5A2 gene. We show that in the absence of prostatic SRD5A2 where the conversion from testosterone to dihydrotesterone (DHT) is blocked, alternate estrogens and estrogenic pathways are upregulated and there is an “androgenic to estrogenic switch”. These findings have broad implications for choosing appropriate classes of medications for management of benign and malignant prostatic diseases.

(Summary submitted by Aria Olumi, MD, and Zongwei Wang, MD, of the Department of Urology)

Press Releases

Massachusetts Off-Road Vehicle Law Significantly Reduces Injuries, Hospitalizations in Children
Featuring Michael Flaherty, DO

Massachusetts General Hospital investigators have found that the 2010 Massachusetts law restricting the use of off-road vehicles to those age 14 and older led to significant reductions in both emergency department visits and hospital admissions resulting from ORV injuries in the following three years.

Gene Variant Could Lead to Missed Type 2 Diabetes Diagnosis in African Americans
Featuring James B. Meigs, MD, MPH

An international research team has identified 60 gene variants that can influence blood levels of hemoglobin A1c, measurements of which are used both to diagnose type 2 diabetes and to monitor blood sugar control. One variant found only in African Americans significantly reduces the accuracy of A1c blood testing, increasing the risk of underdiagnosis in a population known to have a higher risk for the disease.

FDA-Approved Drug May Block Resistance to Anti-Angiogenesis Therapy
Featuring Dai Fukumura, MD, PhD

A Massachusetts General Hospital research team has identified a potential strategy for improving the efficacy of angiogenesis inhibitors, drugs that help fight cancer by blocking the formation of new blood vessels.

People with HIV Who Smoke are More Likely to Die from Lung Cancer than from HIV Itself
Featuring Rochelle Walensky, MD, MPH, and Krishna Reddy, MD

People living with HIV who adhere to antiretroviral therapy but smoke cigarettes are around 10 times more likely to die from lung cancer than from HIV itself, according to a study led by researchers at Massachusetts General Hospital.

Supplemental Nutritional Assistance Program Participation May Reduce Health Care Costs for Low-Income Individuals
 Featuring Seth Berkowitz, MD, MPH

Participation in the Supplemental Nutritional Assistance Program (SNAP, formerly known as the Food Stamp Program) may reduce health care costs for recipients. Researchers found that annual health care costs for recipients were around $1,400 less than for low-income individuals not participating in SNAP.

Achieving National HIV/AIDS Strategy Targets Would Save Lives, Be Cost Effective
Featuring Rochelle Walensky, MD, MPH, and Kenneth Freedberg, MD, MSc

An analysis shows that achieving the treatment targets of the National HIV/AIDS Strategy (NHAS) by 2020 would not only prevent hundreds of thousands of new infections and deaths but also demonstrate excellent value. The study finds that meeting the NHAS goals would save more than two million years of life over the next 20 years.

Blog posts

Evaluating the Impact of Cutbacks to HIV Programs in Resource-Limited Nations
Featuring Rochelle Walensky, MD, MPH, Steve and Deborah Gorlin MGH Research Scholar

Proposed reductions in U.S. foreign aid would have a devastating impact on HIV treatment and prevention programs in countries receiving such aid, an international team of investigators reports.

More Than Hindering Fires—Can Flame Retardants Interfere with Fertility?
Featuring Russ Hauser, MD, MPH, ScD

In a new study published in Environmental Health Perspectives, a team of researchers investigated the potential connection between exposure to flame retardant chemicals found in household products— called PFRs — and pregnancy. While we can’t conclude from the results that products like yoga mats cause infertility, the findings bolster pre-existing research suggesting an association between PFRs and reproductive complications.

Hackathon Revolutionizes Care with Plan to Reduce Deadly Opiate Overdoses
Featuring Benjamin Bearnot, MD, Kristian Olson, MD, and Jessica Moreno, PharmD

When it comes to stopping the deadly effects of an opiate overdose, time is of the essence. Every moment that the brain is deprived of oxygen increases the risk of permanent damage or death. Overdoses can be reversed by administering a drug called Narcan, but the treatment has to be delivered quickly. A team of clinical specialists at Massachusetts General Hospital is hoping to revolutionize the way we respond to overdoses by putting Narcan in the hands of a team of citizen volunteers who are ready to help whenever—and wherever—an overdose happens.

A Snapshot of Science: Detection of Alzheimer's Disease, Development of Type 1 Diabetes and More
Featuring Peter Caravan, PhD, Hua (Jenny) Lu, MD, PhD, Ralph Weissleder, MD, PhD, and Meryem Yucel, PhD

Short summaries of recent research studies from investigators at Massachusetts General Hospital.

Obesity Prevention Researchers Make Strides with First 1,000 Days Program
Featuring Elise Taveras, MD, MPH, Ofer and Shelly Nemirovsky MGH Research Scholar

How early should we start taking steps to prevent childhood obesity? It could be before the baby is even born. That’s the thinking of the research team behind the First 1,000 Days Program, an initiative launched by Massachusetts General Hospital for Children that provides assistance to women during the timeframe believed to be most critical to their child’s health – pregnancy and the first two years after birth.

Researchers and Clinicians Revolutionize Prevention Efforts for Brain Disease
Featuring the work of Jonathan Rosand, MD, and Rudolph Tanzi, PhD

The Institute for Brain Health at Mass General is revolutionizing the way we treat brain disease by developing new strategies for prevention, risk reduction and early treatment. They work with individuals who are at high genetic risk for brain diseases as well as healthy individuals who want to maintain good brain function as they age.

Meet a Mass General Postdoc: Robert Lochhead
Featuring Robert Lochhead, PhD

Robert Lochhead, PhD, is a clinical research fellow for the Center for Immunology and Inflammatory Diseases in the Division of Rheumatology, Allergy & Immunology. He is studying the immunopathology of Lyme arthritis, and the relationship between infection and autoimmunity.

Meet a Mass General Postdoc: Echoe Bouta
Featuring Echoe Bouta, PhD

Echoe Bouta, PhD, is a research fellow in the Edwin L. Steele Laboratories in the Department of Radiation Oncology. Her research looks at lipedema, a chronic lymphatic disorder, in the hopes of catalyzing new treatments for patients with this painful disorder.

Meet a Mass General Postdoc: Xavier Fernando Vela Parada
Featuring Xavier Fernando Vela Parada, MD

Xavier Fernando Vela Parada is a research fellow in the Thadhani Lab within the Division of Nephrology. His research is focused on finding new ways to detect and treat kidney disease.

Meet a Mass General Postdoc: Amy Tsurumi
Featuring Amy Tsurumi, PhD

With the rise of antibiotic-resistant bacteria, doctors need alternative approaches to treat pathogenic diseases. Amy Tsurumi, a research fellow in the Rahme Lab at Mass General, is studying host-microbe interactions to better understand infections and how to treat them.

Thank You Postdocs!

A recap of National Postdoc Appreciation Week.

Could an App Ease the Stress of Managing Heart Failure?
Featuring Nasrien Ibrahim, MD

A new smartphone app was created in the hopes of streamlining cardiac care management for heart failure patients. Now a team at Massachusetts General Hospital wants to test out the app with patients to see if it improves their symptoms and quality of life.

Research Awards and Honors: September 2017
Featuring Aaron Aguirre, MD, PhD, David Chung, MD, PhD, Julie Levison, MD, MPhil, MPH, Fatima Cody Stanford, MD, MPH, MPA, Jennifer Temel, MD, Joseph Greer, PhD, Johnathan Whetstine, PhD, Alik Widge, MD, PhD

A feature of Mass General researchers who received awards and honors in the month of September.

Lady Gaga’s Diagnosis Helps Shed Light on a Perplexing Chronic Pain Disorder
Featuring Marco Loggia, PhD

Lady Gaga has been remarkably open about her struggles with fibromyalgia, a chronic pain disorder that has traditionally been a challenge to diagnose and treat. Researchers at Mass General are hoping to change that by using imaging techniques to demonstrate brain changes in fibromyalgia patients and investigating potential causes for the disease.