Snapshot of Science for June 2021

Welcome to our Snapshot of Science for June 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:

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

Publications

DIABETES TREATMENT COVERAGE IN LOW-INCOME COUNTRIES
The State of Diabetes Treatment Coverage in 55 Low-income and Middle-income Countries: A Cross-sectional Study of Nationally Representative, Individual-level Data in 680 102 Adults
Flood D, Seiglie JA, Dunn M, Tschida S, Theilmann M [et al.], Manne-Goehler J
Published in The Lancet on May 21, 2021 | *Summary available

NEW MOLECULE CAN HELP DIFFERENTIATE AMYLOID BETA SPECIES
Differentiating Aβ40 and Aβ42 in Amyloid Plaques with a Small Molecule Fluorescence Probe
Yang J, Zhu B, Yin W, Han Z, Zheng C [et al.], C Ran
Published in Chemical Science on May 28, 2021 | *Summary available

HIGH BMI ASSOCIATED WITH INCREASED RISK FOR RECURRING BREAST CANCER
Risk Factors for an Advanced Breast Cancer Diagnosis Within 2 Years of a Negative Mammogram
McCarthy AM, Ehsan S, Appel S, Welch M, He W [et al.], Armstrong K
Published in Cancer on June 01, 2021 | *Summary available

INSERTABLE CARDIAC MONITORS IMPROVE DETECTION OF ATRIAL FIBRILLATION
Effect of Long-term Continuous Cardiac Monitoring vs Usual Care on Detection of Atrial Fibrillation in Patients with Stroke Attributed to Large- or Small-Vessel Disease
Bernstein RA, Kamel H, Granger CB, Piccini JP, Sethi PP [et al.], Schwamm LH
Published in JAMA on June 01, 2021 | Press Release

SEX-SPECIFIC CEREBAL LESION ASYMMETRIES AFTER ACUTE ISCHEMIC STROKE
Outcome After Acute Ischemic Stroke Is Linked to Sex-specific Lesion Patterns
Bonkhoff AK, Schirmer MD, Bretzner M, Hong S, Regenhardt RW [et al.], Rost NS
Published in Nature Communications on June 02, 2021 | *Summary available

CELL-CELL COMMUNICATION WITHIN THE GLIOBLASTOMA ECOSYSTEM
Interactions Between Cancer Cells and Immune Cells Drive Transitions to Mesenchymal-like States in Glioblastoma
Hara T, Chanoch-Myers R, Mathewson ND, Myskiw C, Atta L [et al.], Tirosh I
Published in Cancer Cell on June 03, 2021 | *Summary available

FUNDAMENTAL INSIGHTS INTO CELL DIVISION
Differential Regulation of Single Microtubules and Bundles by a Three-protein Module
Mani N, Jiang S, Neary AE, Wijeratne SS, Subramanian R
Published in Nature Chemical Biology on June 03, 2021 | *Summary available

MCAS ARE A MARKER OF IMPAIRED IMMUNITY
Hematopoietic Mosaic Chromosomal Alterations Increase the Risk for Diverse Types of Infection
Zekavat SM, Lin SH, Bick AG, Liu A, Paruchuri K [et al.], Natarajan P
Published in Nature Medicine on June 07, 2021

NOVEL COMPOUND CAN CORRECT SPLICING DEFECT RESPONSIBLE FOR FAMILIAL DYSAUTONOMIA
A Deep Learning Approach to Identify Gene Targets of a Therapeutic for Human Splicing Disorders
Gao D, Morini E, Salani M, Krauson AJ, Chekuri A [et al.], Slaugenhaupt SA
Published in Nature Communications on June 07, 2021 | *Summary available

DECIPHERING THE MECHANISMS OF NONCODING VARIATION
Leveraging Supervised Learning for Functionally Informed Fine-mapping of Cis-eQTLs Identifies an Additional 20,913 Putative Causal eQTLs
Wang QS, Kelley DR, Ulirsch J, Kanai M, Sadhuka S [et al.], Finucane HK
Published in Nature Communications on June 07, 2021

INCREASING HEALTHY FOOD PURCHASES IN THE WORKPLACES
Automated Behavioral Workplace Intervention to Prevent Weight Gain and Improve Diet
Thorndike AN, McCurley JL, Gelsomin ED, Anderson E, Chang Y [et al.], Levy DE
Published in JAMA Network Open on June 07, 2021 | *Summary available | Press Release

ANGINA REMAINS PREVALENT AMONG STABLE OUTPATIENTS WITH CAD
Prevalence of Angina Among Primary Care Patients with Coronary Artery Disease
Blumenthal DM, Howard SE, Searl Como J, O'Keefe SM, Atlas SJ [et al.], Metlay JP
Published in JAMA Network Open on June 07, 2021 | *Summary available

ALL BIOMARKER SUBGROUPS DERIVE BENEFIT FROM SG
Biomarker Analyses in the Phase 3 ASCENT Study of Sacituzumab Govitecan Versus Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer
Bardia A, Tolaney SM, Punie K, Loirat D, Oliveira M [et al.], Hurvitz SA
Published in Annals of Oncology on June 08, 2021 | *Summary available

THERAPEUTIC OPPORTUNITY TO COUNTER THE EFFECTS OF A HIGH-FAT DIET
High-Fat Diet-activated Fatty Acid Oxidation Mediates Intestinal Stemness and Tumorigenicity
Mana MD, Hussey AM, Tzouanas CN, Imada S, Barrera Millan Y [et al.], Yilmaz ÖH
Published in Cell Reports on June 08, 2021

IMMUNE SUPPRESSION DURING SEVERE COVID-19 AND SEPSIS
Plasma from Patients with Bacterial Sepsis or Severe COVID-19 Induces Production of Suppressive Myeloid Cells from Human Hematopoietic Progenitor Cells in Vitro
Reyes M, Filbin MR, Bhattacharyya RP, Sonny A, Mehta A [et al.], Hacohen N
Published in Science Translational Medicine on June 08, 2021 | *Summary available

PHASE 1/2 STUDY OF TREATMENT FOR PATIENTS WITH RET FUSION-POSITIVE NSCLC
Pralsetinib for RET Fusion-positive Non-small-cell Lung Cancer (Arrow): A Multi-cohort, Open-label, Phase 1/2 Study
Gainor JF, Curigliano G, Kim DW, Lee DH, Besse B [et al.], Subbiah V
Published in The Lancet Oncology on June 09, 2021

IDENTIFYING RARE GENETIC VARIANTS EXPECTED TO CAUSE MONOGENIC METABOLIC CONDITIONS
Determinants of Penetrance and Variable Expressivity in Monogenic Metabolic Conditions Across 77,184 Exomes
Goodrich JK, Singer-Berk M, Son R, Sveden A, Wood J [et al.], Udler MS
Published in Nature Communications on June 09, 2021 | *Summary available

VACCINES REMAIN EFFECTIVE AGAINST SARS COV-2 VARIANTS
Immunogenicity of Ad26.Cov2.S Vaccine Against SARS-CoV-2 Variants in Humans
Alter G, Yu J, Liu J, Chandrashekar A, Borducchi EN [et al.], Barouch DH
Published in Nature on June 09, 2021

RELATIONSHIP BETWEEN UNHEALTHY DIETARY PATTERNS AND AN ENHANCED PREVALENCE OF CHIP
Association of Diet Quality with Prevalence of Clonal Hematopoiesis and Adverse Cardiovascular Events
Bhattacharya R, Zekavat SM, Uddin MM, Pirruccello J, Niroula A [et al.], Natarajan P
Published in JAMA Cardiology on June 09, 2021 | *Summary available

RESISTANCE TO APALUTAMIDE IN NONMETASTATIC CASTRATION-RESISTANT PROSTATE CANCER
Blood Biomarker Landscape in Patients with High-Risk Nonmetastatic Castration-Resistant Prostate Cancer Treated with Apalutamide and Androgen-Deprivation Therapy as They Progress to Metastatic Disease
Smith MR, Thomas S, Gormley M, Chowdhury S, Olmos D [et al.], Small EJ
Published in Clinical Cancer Research on June 10, 2021

VITAMIN D REGULATES THE POTENCY OF OPIATE BEHAVIORS
Vitamin D Deficiency Exacerbates UV/Endorphin and Opioid Addiction
Kemény LV, Robinson KC, Hermann AL, Walker DM, Regan S [et al.], Fisher DE
Published in Science Advances on June 11, 2021 | *Summary available | Press Release

DEPRESSION AFTER COVID-19
Factors Associated with Self-reported Symptoms of Depression Among Adults with and Without a Previous COVID-19 Diagnosis
Perlis RH, Santillana M, Ognyanova K, Green J, Druckman J [et al.], Baum MA
Published in JAMA Network Open on June 11, 2021 | *Summary available

FOUR SUBGROUPS FOR BRONCHIOLITIS IDENTIFIED
Integrated Omics Endotyping of Infants with Respiratory Syncytial Virus Bronchiolitis and Risk of Childhood Asthma
Raita Y, Pérez-Losada M, Freishtat RJ, Harmon B, Mansbach JM [et al.], Hasegawa K
Published in Nature Communications on June 14, 2021 | *Summary available | Press Release

NEW INSIGHTS INTO IMPROVING EFFICACY OF CANCER IMMUNOTHERAPY
Expansion of Tumor-associated Treg Cells Upon Disruption of a CTLA-4-Dependent Feedback Loop
Marangoni F, Zhakyp A, Corsini M, Geels S, Carrizosa E [et al.], Mempel T
Published in Cell Press on June 17, 2021 | *Summary available

EFFECT OF SOCIAL DISTANCING AND FACE MASK USE TO PREVENT COVID-19
Association of Social Distancing and Face Mask Use with Risk of COVID-19
Kwon S, Joshi AD, Lo CH, Drew DA, Nguyen LH [et al.], Chan AT
Published in Nature Communications on June 18, 2021

IMMUNE BLOCKING OF CARCINOGEN-EXPOSED BREAST CANCER
CD8 + T Cell Immunity Blocks the Metastasis of Carcinogen-exposed Breast Cancer
Li K, Li T, Feng Z, Huang M, Wei L [et al.], Demehri S
Published in Science Advances on June 18, 2021 | *Summary available | Press Release

ACTIVATION OF TH1 CELLS STRATEGY FOR MELANOMA IMMUNOPREVENTION
Rejection of Benign Melanocytic Nevi by Nevus-Resident CD4 + T Cells
Schiferle E, Cheon S, Ham S, Son H, Messerschmidt J [et al.], Demehri S
Published in Science Advances on June 23, 2021 | *Summary available | Press Release

PROMISING NEW TREATMENT STRATEGY FOR OSTEOPOROSIS
Dual Targeting of Salt Inducible Kinases and CSF1R Uncouples Bone Formation and Bone Resorption
Tang C, Andrade C, O'Meara M, Yoon S, Sato T [et al.], Wein M
Published in elife on June 23, 2021 | *Summary available

NOVEL TREATMENT APPROACH FOR TNBC
RASAL2 Confers Collateral MEK/EGFR Dependency in Chemoresistant Triple-Negative Breast Cancer
Koh S, Ross K, Isakoff S, Melkonjan N, He L [et al.], Ellisen L
Published in American Association for Cancer Research on June 24, 2021 | *Summary available

ROLE OF G9A IN X CHROMOSOME INACTIVATION
A Disproportionate Impact of G9a Methyltransferase Deficiency on the X Chromosome
Szanto A, Aguilar R, Blum R, Wang D, Rojas C, [et al.], Lee J
Published in Genes & Development on June 24, 2021

A SURGERY-FREE ALTERNATIVE TO HISTOPATHOLOGY
Assessing the Impact of Aging and Blood Pressure on Dermal Microvasculature by Reactive Hyperemia Optical Coherence Tomography Angiography
Wang-Evers M, Casper MJ, Glahn J, Luo T, Doyle AE [et al.], Manstein D
Published in Nature Scientific Reports on June 28, 2021 | *Summary available

Publication Summaries

Diabetes is a major global public health challenge, and 80% of people with diabetes live in low-income or middle-income countries (LMICs). Using nationally representative surveys from >680k adults in 55 LMICs, we assessed self-reported coverage of six treatments recommended for people with diabetes including, drug therapy with (1) glucose-lowering, (2) anti-hypertensive, and (3) cholesterol-lowering medications as well as lifestyle counseling on (4) diet, (5), exercise, and (6) weight-loss. We found that fewer than one in 10 people with diabetes in these settings received all services. Coverage of glucose lowering medications was about 50%, and much greater than antihypertensives at 40% or cholesterol lowering medications at 6%. Approximately one in three people with diabetes received each form of lifestyle counseling.

(Summary submitted by Jennifer Manne-Goehler, MD, ScD, ScM, Division of Infectious Diseases, Department of Medicine)

Amyloid beta (Aβ) plaque is one of the characteristic biomarkers for Alzheimer's disease (AD). Differentiating species of Aβ40 and Aβ42 can considerably clarify the role of plaque in AD pathology. Unfortunately, small-molecule probes with such capacity are scarce. In the present study, we report a small-molecule probe ICTAD-1 that can fluorescently differentiate Aβ40 and Aβ42 in solution, brain tissue slides and transgenic AD mice. We believe that ICTAD-1 can be used as an important tool for basic studies and has the potential to provide a better diagnosis in the future.

(Summary submitted by Biyue Zhu, PhD, Department of Radiology, Martinos Center)

We evaluated the risk of poor prognosis breast cancer, that is, breast cancer with advanced stage, large size, spread to lymph nodes or other tissues, or aggressive subtype among women who underwent mammography screening at Mass General from 2006 to 2015. We found that women who had higher body mass index had higher risk of developing poor prognosis breast cancers within two years of a negative mammogram. These results suggest that overweight and obese women should consider annual mammography or supplemental screening with breast MRI to improve early detection.

(Summary submitted by Anne Marie McCarthy, ScM, PhD, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine)

Acute ischemic stroke affects men and women differently. Here, we designed a novel statistical framework to investigate sex differences in how various stroke lesion patterns relate to acute stroke severity. Employing this framework to two independent cohorts (n=555, n=503), we found that lesions in motor and language areas help explain stroke severity in both men and women. However, women were characterized by more widespread patterns. Lesions in the left posterior circulation were detrimental, specifically in women. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute stroke.

(Summary submitted by Anna Bonkhoff, MD, Department of Neurology, J. Philip Kistler Stroke Research Center)

Glioblastoma is the most common and lethal form of brain cancer. Despite the growing awareness that the diversity of molecules and cells in this disease confounds successful treatments, how to overcome the problems remains unclear. In this work, we describe cell-cell communication within the glioblastoma ecosystem and find that immune cells are involved in shaping such heterogeneous aspects of this disease. By characterizing the mechanisms behind the cellular communications, we point out a new approach to improve the efficacy of immunotherapy.

(Summary submitted by Toshiro Hara, PhD, Department of Pathology, Mass General Cancer Center)

When a human cell divides, it physically cleaves through its middle to form two identical daughter cells. Errors in this process result in cells with incorrect DNA content, a hallmark of tumor formation. How does a dividing cell find its middle? Inside a cell, long rod-like filaments called microtubules assemble into a platform of precise width to mark the cell center. This assembly requires fine control of microtubule length by a host of cellular proteins. Our study reveals a minimal protein module that recapitulates microtubule organization at the cell center and provides fundamental insights into the processes of cell division.

(Summary submitted by Nandini Mani, PhD, and Radhika Subramanian, PhD, Department of Molecular Biology)

Splicing is a highly regulated process through which non-coding regions of a gene are removed and coding regions are joined to generate a mature messenger RNA. Many human hereditary diseases are caused by mutations affecting this process. In this study, we identified a novel compound able to correct the splicing defect responsible for familial dysautonomia. Moreover, we developed a deep learning framework that enabled us to predict significant expansion of its therapeutic potential to other splicing disorders. We then validated several of our computational predictions of therapeutic targets by demonstrating successful amelioration of splicing defects in cellular models of cystic fibrosis, familial frontotemporal dementia, cholesterol ester storage disease and Lynch syndrome. Our study shows the tremendous value in the application of novel machine learning approaches to accelerate drug development.

(Summary submitted by Elisabetta Morini, PhD, and Dadi Gao, PhD, Department of Neurology, Center for Genomic Medicine)

Personalized interventions that leverage workplace data and environments could improve the effectiveness of employee wellness programs. ChooseWell 365 was a randomized clinical trial conducted among 602 Mass General employees who used hospital cafeterias. The intervention group received two emails per week with personalized feedback about cafeteria purchases and one letter per month with peer comparisons and financial incentives for healthier purchases. Emails and letters were automatically generated and delivered over 12 months. Results showed no between-group differences in weight change at 12- or 24-month follow-up. The intervention group increased healthy food purchases significantly during the 12-month intervention and sustained improvements through 24-month follow-up.

(Summary submitted by Anne Thorndike, MD, MPH, Department of Medicine, Tobacco Research and Treatment Center)

Angina pectoris—a symptom of coronary artery disease (CAD)—is associated with increased morbidity and health care spending. The prevalence of angina among contemporary outpatient populations with CAD remains incompletely defined. We evaluated the prevalence of angina symptoms among outpatients with CAD who receive primary care at one of 15 Massachusetts General Hospital primary care clinics and community health centers. We assessed angina using the Seattle Angina Questionnaire-7 (SAQ-7), a validated seven-question survey instrument for assessing angina. Approximately 21% of surveyed patients reported at least monthly angina, suggesting that angina remains prevalent among stable outpatients with CAD. Routine assessment of angina symptoms in stable outpatients with CAD may help identify patients at heightened risk for future morbidity.

(Summary submitted by Summary submitted by Daniel Blumenthal, MD, MBA, Division of Cardiology, Department of Medicine)

The landmark phase III ASCENT trial demonstrated improved survival associated with sacituzumab govitecan (SG), an anti-Trop-2 antibody-drug conjugate linked with topoisomerase-inhibitor SN-38, over single-agent chemotherapy of physician’s choice (TPC) in metastatic triple-negative breast cancer. In this study, we evaluate association between Trop-2 expression and clinical outcomes. Overall, the median progression-free survival was 6.9, 5.6, and 2.7 months for high, medium, and low Trop-2 H-scores, respectively with SG compared with 2.5, 2.2, and 1.6 months with TPC. The study confirmed that all biomarker subgroups derive benefit from SG as compared to standard chemotherapy.

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

NEW INSIGHT INTO IMMUNE SUPPRESSION DURING SEVERE COVID-19 AND SEPSIS
Plasma from Patients with Bacterial Sepsis or Severe COVID-19 Induces Production of Suppressive Myeloid Cells from Human Hematopoietic Progenitor Cells in Vitro
Reyes M, Filbin MR, Bhattacharyya RP, Sonny A, Mehta A [et al.], Hacohen N
Published in Science Translational Medicine on June 08, 2021

Patients with severe COVID-19 sometimes progress to sepsis, a life-threatening syndrome associated with dysfunction of the immune system. A new collaborative study involving investigators at Mass General, Brigham and Women’s Hospital and the Broad Institute offers new insight into immune suppression during severe COVID-19 and sepsis. In patients with severe COVID-19, cytokines such as interleukin-6 induce production of dysfunctional myeloid cells, which suppresses the immune system in particular T cells. This work suggests that targeting these cells could one day improve outcomes in many kinds of severe infections.

(Summary submitted by Nir Hacohen, PhD, Center for Cancer Immunology, Mass General Cancer Center)

For most genetic variants reported to cause severe monogenic diseases, the probability that a person born with the genetic variant develops the expected disease (termed penetrance) is unknown. We assessed 77,184 adult individuals to identify people with rare genetic variants expected to cause eight metabolic conditions and then determined whether these people manifested the expected clinical features. On average, 60% or fewer the people with the rare variants displayed clinical features consistent with their expected conditions. We also found that accounting for someone’s common genetic variation in addition to rare genetic variation improved ability to predict at least two of these metabolic conditions. Our findings indicate that interpretation of clinical monogenetic testing can be improved by incorporating additional genetic information.

(Summary submitted by Miriam Udler, MD, PhD, Division of Endocrinology, Department of Medicine, Center for Genomic Medicine)

Clonal hematopoiesis of indeterminate potential (CHIP) is a disease of aging where hematopoietic stem cells (HSCs) accumulate mutations throughout the lifetime and increase the risk of both leukemia and cardiovascular disease. By analyzing the genomes and dietary habits of 44,111 individuals in the UK Biobank, we demonstrated a relationship between unhealthy dietary patterns and an enhanced prevalence of CHIP. Furthermore, unhealthy diet additively increased risk of future cardiovascular events while patients with CHIP and a healthy diet had better prognosis than those without. Our findings will prompt further study into whether dietary habits contribute to the development of CHIP, or whether specific dietary patterns are important in risk mitigation among those with CHIP.

(Summary submitted by Romit Bhattacharya, MD, Division of Cardiology, Department of Medicine)

Previous work revealed that UV irradiation triggers production of cutaneous endorphin and opiate-like responses. The current study found that vitamin D, which is also produced in response to UV, regulates the potency of opiate behaviors. Vitamin D deficiency strongly amplified opiate dependency, withdrawal and other endpoints in lab mice. Vitamin D deficiency also correlated with likelihood of human opiate use in a large hospital database and likelihood of opiate use disorder diagnosis. Importantly, the study found that correction of vitamin D deficiency through oral supplementation corrected the addiction-related risk in mice, suggesting a public health opportunity to combat addiction.

(Summary submitted by David E. Fisher, MD, PhD, Cutaneous Biology Research Center, Department of Dermatology, Mass General Cancer Center)

We drew on data from a 50-state survey conducted approximately every month since spring 2020. As part of the survey, respondents complete a depression screening measure. We found that depression was somewhat different, on average, among people who had previously been diagnosed with COVID-19, compared to those who had not. For example, risk factors were different (greater risk for men than women, the opposite of what we would expect for depression in general) and symptoms were different, with more motor restlessness or slowing and more thoughts of suicide among depressed people with prior COVID-19. Our study suggests that, while depression is common after COVID-19, it may be somewhat different from typical major depression.

(Summary submitted by Roy H. Perlis, MD, MSc, Department of Psychiatry, Center for Quantitative Health, Center for Genomic Medicine)

Bronchiolitis—the most common lung infection in infants—is most often caused by respiratory syncytial virus (RSV). About 30% of infants with severe bronchiolitis later develop asthma. However, clinicians have been unable to identify subgroups that have distinct molecular characteristics and a higher risk for asthma. From 221 infants hospitalized with RSV bronchiolitis, we gathered information on the microbes, metabolites, and immune response–related molecules present in nasal passages. We identified four biologically meaningful subtypes of RSV bronchiolitis. One subtype—characterized by rhinovirus coinfection, dominance by specific bacteria and high interferon (anti-viral defense proteins) response—had an approximately 40% risk for asthma by age five.

(Summary submitted by Yoshihiko Raita, MD, MMSc, MPH, Department of Emergency Medicine)

In this study we observed that CTLA-4-targeted immune checkpoint blockade, a popular form of cancer immunotherapy, can inadvertently hyperactivate and expand tumor-infiltrating T regulatory (Treg) cells in mouse models of cancer, partially off-setting its therapeutic efficacy. This effect resulted from the interruption of a negative feedback mechanism through which Treg cells self-regulate to adjust their immune-suppressive activities to the degree to which they have already regulated an immune response. The feedback loop may physiologically serve to prevent Treg cell-mediated over-regulation of anti-pathogen responses, which could otherwise be shut down before a pathogen is eliminated or controlled. Our findings indicate that CTLA-4 targeted immunotherapy in cancer patients may be even more effective when combined with treatments that target Treg cells in tumors.

(Summary submitted by Thorsten Mempel, MD, PhD, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Center for Immunology and Inflammatory Diseases)

Emerging evidence indicates that immunogenicity (i.e., improved response to immunotherapies) is a hallmark of cancers caused by exposure to environmental carcinogens. But in the past, science has focused mainly on the mutations caused by these exposures in a patient’s DNA as the reason for the immune attack. Our team describes, for the first time, a distinct consequence of carcinogen exposure that can have significant immunologic implications: the nongenetic induction of an immune factor called CCL21 in breast cancer cells that were exposed to a carcinogen. This finding could open the door to therapeutic interventions to improve response to current cancer treatments.

(Summary submitted by Shawn Demehri, MD, PhD, Cutaneous Biology Research Center, Department of Dermatology; and Center for Cancer Immunology, Mass General Cancer Center)

Melanocytic nevi (common moles) are benign skin lesions that share characteristics with melanoma. We determined that a subset of white blood cells known as CD4+ T cells that reside in the mole tissue can be activated to eradicate the mole. We believe that these same T cells could be activated to prevent and treat melanoma. Importantly, these T cells have a “memory” phenotype and can be promptly activated for the protection against cancer recurrence long term. Not only does this study have implications in the scope of melanoma, but it also suggests that other endogenous killer CD4+ T cells specific to other immunogenic targets may be able to help overcome the obstacles to current cancer immunotherapies for other types of cancer.

(Summary submitted by Erik Schiferle, Department of Dermatology and Mass General Cancer Center)

In osteoporosis, loss of bone mass causes weak bones that are more likely to fracture. Osteoporosis therapies can either slow down bone destruction or accelerate bone formation. All current treatments that speed up bone formation require frequent injections and therefore are somewhat problematic for this chronic, asymptomatic disease. Orally available drugs that inhibit salt inducible kinases (SIKs) represent a promising new way to treat osteoporosis. In this study, a SIK inhibitor enhanced bone formation and blocked bone resorption. This promising profile was due to inhibition of two distinct targets in different cells in bone, representing a novel treatment strategy for osteoporosis.

(Summary submitted by Marc Wein, MD, PhD, Division of Endocrinology, Department of Medicine)

Triple-negative breast cancer (TNBC) is an aggressive subtype for which the mainstay of treatment is chemotherapy. Unfortunately, there are currently no clinically used biomarkers that distinguish sensitive from resistant tumors, and no established alternative therapeutic options for chemo-resistant cases. Through analysis of clinical trial specimens, we discovered RASAL2 as a factor that identifies TNBCs that are resistant to standard chemotherapy but also exhibit a surprising sensitivity to targeted inhibitors of certain growth factors receptor pathways. We showed how RASAL re-wires cell signaling to cause this therapeutic vulnerability, all of which suggests the potential clinical utility of this new treatment approach selectively for RASAL2-high TNBC

(Summary submitted by Leif Ellisen, MD, PhD, Division of Hematology/Oncology, Department of Medicine, Mass General Cancer Center)

While conventional optical coherence tomography angiography (OCT-A) is limited to only capturing the structure of actively perfused vessels, the reactive hyperemia OCT-A (RH-OCT-A) method non-invasively visualizes the dermal microvascular network at peak perfusion. The results of RH-OCT-A correlate with histopathology and both techniques capture age and blood pressure related capillary rarefaction. However, only OCT-A and RH-OCT-A show an age-related reduction of the dermal microvascular thickness. Additionally, we introduced the optically derived relative capillary capacity as a quantitative metric that strongly correlates with systolic blood pressure and may help to characterize disease progression and vascular health.

(Summary submitted by Michael Wang-Evers, PhD, Cutaneous Biology Research Center, Department of Dermatology)

Press Releases

Chip Inserted Under the Skin May Better Identify Patients at Risk of Recurrent Stroke
Featuring Lee Schwamm, MD

For patients who have experienced certain common types of stroke, a small chip inserted under the skin may help physicians predict the likelihood of a second stroke, and therefore their likelihood of benefiting from preventive therapy.

Feedback on Cafeteria Purchases Helps Employees Make Healthier Food Choices
Featuring Anne N. Thorndike, MD, MPH

Automated emails and letters that provide personalized feedback related to cafeteria purchases at work may help employees make healthier food choices.

Study Reveals Changes in Cigarette Smoking During the COVID-19 Pandemic
Featuring Nancy Rigotti, MD

Last year, people who smoked had a variety of responses to the COVID-19 pandemic, with some increasing their smoking to help them cope and others quitting to potentially lessen their vulnerability to COVID-19.

New Study Underscores the Role of Race and Poverty in COVID-19
Featuring Marcela del Carmen, MD, and Jason Wasfy, MD, MPhil

A new analysis offers a novel perspective on the disproportionate impact that COVID-19 has had on people of color, low-income populations and other structurally disadvantaged groups.

Vitamin D Deficiency May Increase Risk for Addiction to Opioids and Ultraviolet Rays
Featuring David E. Fisher, MD, PhD

Vitamin D deficiency strongly exaggerates the craving for and effects of opioids, potentially increasing the risk for dependence and addiction, according to a new study.

Common Lung Infection in Infants Has Different Subtypes With Differing Asthma Risks
Featuring Yoshihiko Raita, MD, MPH, MMSc

A team led by Mass General investigators has uncovered four distinct molecular subtypes of RSV bronchiolitis and has linked a certain subtype to a higher asthma risk.

Carcinogen-Exposed Cells Provide Clues in Fighting Treatment-Resistant Cancers
Featuring Shadmehr (Shawn) Demehri, MD, PhD

Researchers have discovered a biological mechanism that transforms cells exposed to carcinogens from environmental factors like smoking and ultraviolet light into immunogenic cells that can be harnessed therapeutically to fight treatment-resistant cancers.

An Unexpected Discovery: Inflammatory Proteins May Slow Cognitive Decline in Aging Adults
Featuring Rudolph Tanzi, PhD

Researchers have found that two proteins that help regulate inflammation may slow cognitive decline in aging adults. This discovery may lend support for an emerging theory about the cause of Alzheimer’s disease.

Skin Reactions After COVID-19 Vaccination: Rare, Uncommonly Recur After Second Dose
Featuring Kimberly G. Blumenthal, MD, MSc

Skin problems after a first mRNA COVID-19 vaccine dose occurred in 1.9% of surveyed employees from the Mass General Brigham hospital system. Among employees who experienced a skin reaction to the first dose, 83% had no recurrence of symptoms following the second dose.

Common Moles Could Serve as Players in Battling Melanoma and Preventing Its Recurrence
Featuring Shadmehr (Shawn) Demehri, MD, PhD

Researchers have found that a subset of white blood cells known as CD4+ T cells reside naturally in moles on the body and could be activated as part of a novel strategy to treat melanoma and generate a potent immunity against its recurrence.

Further Hope for BCG Vaccine in Stemming Type 1 Diabetes
Featuring Denise Faustman, MD, PhD

At the Annual Scientific Sessions of the American Diabetes Association, researchers presented positive updates on their trials of the bacillus Calmette-Guérin (BCG) vaccine to safely and significantly lower blood sugars.

Blog Posts

New Software Promotes Inclusivity in Genetic Research and Strengthens Study Results
Featuring Elizabeth Atkinson, PhD

Dr. Atkinson and her team are working to make genetic research more inclusive with a new statistical framework and software package designed to include individuals of mixed ancestry.

Decrease in Internet Searches for Cancer Screening Terms During COVID Sparks Concerns of Delayed Diagnoses
Featuring Austin Snyder and Brent Little, MD

Researchers are worried that delayed cancer screenings due to COVID-19 could lead to later diagnoses and more severe cases.

Meet Our Newest Intern, Isha!
Featuring Isha Vedantam

Isha is a graduate student at BU studying public health to help people through health challenges in their lives that they may not be prepared for.

Alzheimer’s and Brain Awareness Month 2021: Spotlighting Mass General Alzheimer’s Researchers (Part 1)

Learn how Mass General researchers are working to develop new treatments and diagnostic tools for Alzheimer’s disease and dementia. Here we spotlight the word of Amar Sahay, PhD, and Florence Lai, MD.

Alzheimer’s and Brain Awareness Month 2021: Spotlighting Mass General Alzheimer’s Researchers (Part 2)

In the second installment, we highlight two more approaches to Alzheimer’s research with Susanne Janneke Van Veluw, PhD, and Mehdi Jorfi, PhD.

Congratulations to the 2021 Class of Bridging Academia with Industry

The translational research training program and accompanying project competition seeks to create a new culture of research collaboration.

Conversations with Margarita: The Future of the American Dream
Featuring Margarita Alegría, PhD

While they drive our economy and society forward, people who immigrate to the United States also have to navigate new systems, cultural norms and sometimes a new language.

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Snapshot of Science for June 2021