Snapshot of Science for March 2023

Welcome to our Snapshot of Science for March 2023.

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:

26 new studies published in high-impact journals, along with 22 summaries submitted by the research teams
12 new research-related press releases
14 posts from the Mass General Research Institute blog
4 research spotlights

Publications

Path to Developing Regenerative Cell Therapies to Treat Neurointestinal Diseases
Single-cell Multiome Sequencing Clarifies Enteric Glial Diversity and Identifies an Intraganglionic Population Poised for Neurogenesis
Guyer RA, Stavely R, Robertson K, Bhave S, Mueller JL [et al.], Goldstein AM
Published in Cell Reports on 28-Feb | *Summary available

Uncovering an Essential GNAS Imprinting Control Mechanism
The Long-range Interaction Between Two GNAS Imprinting Control Regions Delineates Pseudohypoparathyroidism Type 1B Pathogenesis
Iwasaki Y, Aksu C, Reyes M, Ay B, He Q, Bastepe M
Published in Journal of Clinical Investigation on 28-Feb | *Summary available

Palbociclib Not Effective at Treating Nonbreast Solid Tumors
Phase II Study of Palbociclib (PD-0332991) in CCND1, 2, or 3 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1B
Clark AS, Hong F, Finn RS, DeMichele AM, Mitchell EP [et al.], Flaherty KT
Published in Clinical Cancer Research on 28-Feb

Researchers Bioengineer an Endocrine Pancreas for Type 1 Diabetes
Bioengineered Omental Transplant Site Promotes Pancreatic Islet Allografts Survival in Non-human Primates
Deng H, Zhang A, Pang DRR, Xi Y, Yang Z [et al.], Lei J
Published in Cell Reports Medicine on 1-Mar | *Summary available | Press Release

New Ways to Boost Active Vitamin D Levels in Patients with Chronic Kidney Disease
A Parathyroid Hormone/Salt-inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis
Yoon SH, Meyer MB, Arevalo Rivas C, Tekguc M, Zhang C [et al.], Wein MN
Published in Journal of Clinical Investigation on 2-Mar | *Summary available

Artificial Intelligence Approach May Help Detect Alzheimer's Disease from Routine Brain Imaging Tests
Adversarial Confound Regression and Uncertainty Measurements to Classify Heterogeneous Clinical MRI in Mass General Brigham
Leming M, Das S, Im H
Published in PLoS One on 2-Mar | *Summary available | Press Release

Findings May Help Decision-making for Optimally Integrating Immunotherapies with Radiotherapy
Systemic Immune Modulation by Stereotactic Radiotherapy in Early-stage Lung Cancer
Gkika E, Firat E, Adebahr S, Graf E [et al.], Duda DG, Grosu AL
Published in NPL Precision Oncology on 2-Mar | *Summary available

Role of Intestinal Fibrosis in Inflammatory Bowel Disease
Stiffness Restricts the Stemness of the Intestinal Stem Cells and Skews Their Differentiation Towards Goblet Cells. Gastroenterology
He S, Lei P, Kang W, Cheung P, Xu T [et al.], Saeidi N
Published in Gastroenterology on 3-Mar | *Summary available | Press Release

New Liquid Biopsy Technique With Potentially Increased Diagnostic Accuracy
Multiplexed Analysis of EV Reveals Specific Biomarker Composition with Diagnostic Impact
Spitzberg JD, Ferguson S, Yang KS, Peterson HM, Carlson JCT, Weissleder R
Published in Nature Communications on 4-Mar | *Summary available

Cost-effectiveness of Using SGLT2-I to Prevent Heart Failure
Cost-effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors for the Treatment of Heart Failure With Preserved Ejection Fraction
Cohen LP, Isaza N, Hernandez I, Lewis GD, Ho JE [et al.], Bellows BK
Published in JAMA Cardiology on 4-Mar | *Summary available

Genetic Origins of Cerebral Arachnoid Cysts
Multiomic Analyses Implicate a Neurodevelopmental Program in the Pathogenesis of Cerebral Arachnoid Cysts
Kundishora AJ, Allington G, McGee S, Mekbib KY, Gainullin V [et al.], Kahle KT
Published in Nature Medicine on 6-Mar | *Summary available

How Propofol Impacts Perceptual and Cognitive Processing
Propofol Disrupts Alpha Dynamics in Functionally Distinct Thalamocortical Networks During Loss of Consciousness
Weiner VS, Zhou DW, Kahali P, Stephen EP, Peterfreund RA [et al.], Purdon PL
Published in PNAS on 10-Mar

Normalizing Tumor Blood Vessels May Improve Immunotherapy Against Brain Cancer
Anti-VEGF Therapy Improves EGFR-vIII-CAR-T Cell Delivery and Efficacy in Syngeneic Glioblastoma Models in Mice
Dong X, Ren J, Amoozgar Z, Lee S, Datta M [et al.], Jain RK
Published in Journal for the ImmunoTherapy of Cancer on 10-Mar | *Summary available | Press Release

Mortality Gap Widened between Homeless Cohort and General Population
Mortality Trends Among Adults Experiencing Homelessness in Boston, Massachusetts From 2003 to 2018
Dickins KA, Fine DR, Adams LD, Horick NK, Lewis E, Looby SE, Baggett TP
Published in JAMA Internal Medicine on 13-Mar | *Summary available

Black, Hispanic, and Asian Children Underrepresented in Clinical Trials
Race and Ethnicity Reporting and Representation in Pediatric Clinical Trials
Brewster RCL, Steinberg JR, Magnani CJ, Jackson J, Wong BO [et al.], Turner B
Published in Pediatrics on 14-Mar | *Summary available

Promising New Class of Transferrin-targeted Iron Replacement Drugs
A Rationally Designed Complex Replenishes the Transferrin Iron Pool Directly and with High Specificity
Sargun A, Fisher AL, Wolock AS, Phillips S, Sojoodi M [et al.], Gale EM
Published in Journal of the American Chemical Society on 15-Mar

New Patient-centered Outcome Measure of Critically Ill Patients
Association of Days Alive and at Home at Day 90 After Intensive Care Unit Admission With Long-term Survival and Functional Status Among Mechanically Ventilated Patients
Taran S, Coiffard B, Huszti E, Li Q, Chu L [et al.], Goligher EC
Published in JAMA Network Open on 16-Mar | *Summary available

Black Residents Performed Significantly Fewer Surgical Cases than White Residents
Racial and Ethnic Disparities in Operative Experience Among General Surgery Residents: A Multi-Institutional Study from the US ROPE Consortium
Eruchalu CN, Etheridge JC, Hammaker AC, Kader S, Abelson JS [et al.], Cortez AR
Published in Annals of Surgery on 17-Mar | *Summary available

New Gene Therapy Approach for Protein Deficiency in Neurons of Patients with Neurodegenerative Diseases
Mechanism of STMN2 Cryptic Splice-polyadenylation and its Correction for TDP-43 Proteinopathies
Baughn MW, Melamed Z, López-Erauskin J, Beccari MS [et al.], Lagier-Tourenne C, Cleveland DW
Published in Science on 17-Mar | *Summary available | Press Release

New Model Proposed to Mimic Nonenzymatic Rna Replication During the Origin of Life
Experimental Tests of the Virtual Circular Genome Model for Nonenzymatic RNA Replication
Ding D, Zhou L, Mittal S, Szostak JW
Published in Journal of American Chemical Society on 24-Mar

Association Between Elevated Levels of Circulating Ghrelin and Prospective Weight Gain in Girls and Women with Anorexia Nervosa
Association Between Ghrelin and Body Weight Trajectory in Individuals With Anorexia Nervosa
Kim YR, Lauze MS, Slattery M, Perlis RH, Holsen LM [et al.], Eddy KT
Published in JAMA Network Open on 24-Mar | *Summary available

SARS‐CoV‐2 Infection During Pregnancy Linked to Higher Risk of Neurodevelopmental Disorders in Male Infants
Sex-Specific Neurodevelopmental Outcomes Among Offspring of Mothers With SARS-CoV-2 Infection During Pregnancy
Edlow AG, Castro VM, Shook LL, Haneuse S, Kaimal AJ, Perlis RH
Published in JAMA Network Open on 23-Mar | *Summary available | Press Release

Web Application to View and Annotate Slide Microscopy Images Using the Internationally Accepted Standard for Medial Digital Imaging
Interoperable Slide Microscopy Viewer and Annotation Tool for Imaging Data Science and Computational Pathology
Gorman C, Punzo D, Octaviano I, Pieper S, Longabaugh WJR [et al.], Herrmann MD
Published in Nature Communications on 22-Mar | *Summary available

Importance of Intrinsic Mechanisms of Heterogeneity Across Human Cancers
Cellular Mechanisms of Heterogeneity in NF2-mutant Schwannoma
Chiasson-MacKenzie C, Vitte J, Liu CH, Wright EA, Flynn EA [et al.], McClatchey AI
Published in Nature Communications on 21-Mar

Associations Between Genetically-determined Left Ventricular Mass and Future Heart Disease
Clinical and Genetic Associations of Deep Learning-derived Cardiac Magnetic Resonance-based Left Ventricular Mass
Khurshid S, Lazarte J, Pirruccello JP, Weng LC, Choi SH [et al.], Lubitz SA
Published in Nature Communications on 21-Mar | *Summary available

Boosting the Body’s Anti-viral Immune Response May Eliminate Aging Cells
Cytotoxic CD4+ T Cells Eliminate Senescent Cells by Targeting Cytomegalovirus Antigen
Hasegawa T, Oka T, Son HG, Oliver-García VS, Azin M [et al.], Demehri S
Published in Cell on 30-Mar | *Summary available | Press Release

Publication Summaries

The enteric nervous system, which controls all aspects of gastrointestinal (GI) function, is made up of two types of cells: neurons and glia. Abnormal or missing neurons can lead to several serious GI diseases, including Hirschsprung disease. Our laboratory is working to develop stem cell therapy as a novel strategy to replace those neurons and restore normal GI function. Using advanced single-cell sequencing technology and traditional cell biology methods, in this study we found that enteric glial cells are a heterogeneous cell population comprising multiple subtypes, including one that is capable of rapidly switching its glial identity to become a neuron. This surprising and exciting result paves a path to developing regenerative cell therapies to treat neurointestinal diseases.

(Summary submitted by Allan M Goldstein, MD, Department of Surgery)

GNAS is a critical gene in hormone action and is involved in many diseases. Between two parental GNAS genes, the mother’s gene has a larger contribution than the father’s, known as “genomic imprinting.” Imprinting defects in GNAS cause a disorder of hormone resistance, pseudohypoparathyroidism type 1B (PHP1B). We used genome editing to generate a human embryonic stem cell model of PHP1B, enabling us to identify an essential interaction between two distant genetic regions necessary for proper GNAS imprinting. Our findings delineate the PHP1B pathogenesis and apply broadly to GNAS-related diseases and other genomic imprinting disorders.

(Summary submitted by Yorihiro Iwasaki, PhD, Endocrine Unit, Department of Medicine)

Transplanting islets to the liver to treat type 1 diabetes is not efficient. Scientists are looking for alternative sites, and one promising location is the omentum, a fatty tissue in the abdomen. To use the omentum, we developed a method to immobilize donor islets onto it using a bio-degradable matrix. We tested this method on nonhuman primates with type 1 diabetes and found that it can normalize blood glucose levels and restore insulin secretion for long term. The method aids in the process of revascularization and reinnervation for the transplanted islets, which results in complete glycemic control.

(Summary submitted by Ji Lei, MD, MBA, MSc, Center for Transplantation Sciences, Department of Surgery)

To exert its many biologic effects, vitamin D must first be activated in the kidney. This pathway is important in healthy individuals, and is defective in patients with chronic kidney disease. In this step, investigators used cutting-edge methods to understand how cells in the kidney respond to hormonal cues to increase vitamin D activation. A signaling cascade was defined that involves key enzymes called salt inducible kinases (SIKs). These enzymes normally restrain vitamin D production. When SIKs are inhibited by hormonal signals, vitamin D activation occurs. This model suggests new ways to boost active vitamin D levels in patients with chronic kidney disease and associated bone and vascular abnormalities.

(Summary submitted by Marc Wein, MD, PhD, Endocrine Unit, Department of Medicine)

A new computer model detects Alzheimer's/dementia status in tens of thousands of routinely collected clinical brain MRIs. It uses advanced deep learning methods to both determine the uncertainty of diagnostic predictions, which aids in effective cross-institutional applications, as well as regression of confounding factors, such as patient age, from the prediction process.

(Summary submitted by Matthew Leming, PhD, Center for Systems Biology)

Radiotherapy and immunotherapy are standard therapies for treating lung cancer. Combining them may lead to synergy or antagonism. This study examined the effect of ablative hypofractionated radiotherapy on effector lymphocyte subsets over time in early-stage lung cancer patients. Furthermore, it examined the impact of using different doses per fraction of radiotherapy. The study revealed that radiotherapy could increase the fraction of proliferating CD4+ and CD8+ circulating T cells. This effect was detectable at the end of treatment and only in the patients who received radiotherapy at 10Gy or less per fraction. These findings may help decision-making for optimally integrating immunotherapies with radiotherapy.

(Summary submitted by Dan G. Duda, DMD, PhD, Division of Radiation Oncology, Edwin L. Steele Laboratories for Tumor Biology)

Intestinal fibrosis is a hallmark of inflammatory bowel disease (IBD), and the primary cause of end-stage organ failure. Yet, it is unclear how the fibrosis influences IBD progression. To address it, we developed a novel platform for culturing intestinal stem cells that closely mimics the native tissue. We demonstrated that tissue stiffening that is caused by fibrosis reduces the population and stemness of the stem cells and promotes their differentiation towards goblet cells. These results have direct implications in the pathogenesis of IBD and identify the mechanosignaling pathways as a potential therapeutic target for it.

(Summary submitted by Nima Saeidi, PhD, Center for Engineering in Medicine & Surgery, Department of Surgery)

Liquid biopsies are a type of blood test that can potentially diagnose cancer and other diseases non-invasively. Different types of liquid biopsies are being explored but the analysis of exosomes is generally thought to be most promising given their abundance in the blood. Up to now, it has been difficult to analyze these very small vesicles for the presence of multiple defining protein markers. Here we developed a multiplexed analysis of single exosome (MASEV) technique to interrogate thousands of individual exosomes for 15 EV biomarkers. These findings establish the potential of MASEV for uncovering fundamental exosome biology and increasing their diagnostic accuracy.

(Summary submitted by Ralph Weissleder, MD, PhD, Center for Systems Biology)

SGLT2-inhibitors improve cardiac outcomes in patients with heart failure with preserved ejection fraction (HFpEF), but the medication’s economic value, which is assessed via a cost-effectiveness analysis, has not been described before. In a recent such analysis, we found adding SGLT2-inhibitors for patients with HFpEF increased quality-adjusted life years by 0.19, which is approximately 69 healthy days of life, at a lifetime cost of $26,000. The incremental cost-effectiveness ratio was $141,300, which corresponds to “intermediate value” based on pre-defined standards. Current wholesale drug prices would need to be decreased by 78% to reach the threshold for “high value.”

(Summary submitted by Laura P. Cohen, MD, Division of Cardiology, Department of Medicine)

Arachnoid cysts (ACs) are the most common mass in the human skull. Our study found that mutations damaging genes that control gene activity in development, before birth, of the brain and brain-covering may cause some ACs. We also used artificial intelligence to group patients based on similar symptoms and found that groups with more symptoms had more patients with mutations. Many of these mutated genes are also mutated in autism and seizure disorders, both common conditions in AC, suggesting some AC symptoms will not improve with surgery because they’re caused by a deeper genetic issue and require different treatment.

(Summary submitted by Kedous Y. Mekbib, Yale School of Medicine)

We have previously shown that blocking vascular endothelial growth factor (VEGF) signaling can normalize tumor vessels in multiple murine and human tumors, including glioblastomas, and improve the delivery of CD8+ T cells and the efficacy of immunotherapy in mouse models of breast cancer. Here we demonstrate that treatment with an anti-mouse VEGF antibody improves the infiltration and distribution of CAR-T cells throughout the tumor microenvironment, delays tumor growth and prolongs survival of GBM-bearing mice compared with EGFRvIII-CAR-T cell therapy alone. This finding supports clinical trials to evaluate the combination therapy for GBM, an aggressive cancer that resists all current therapies.

(Summary submitted by Rakesh K. Jain, PhD, E.L. Steele Laboratories, Department of Radiation Oncology)

People experiencing homelessness face substantially higher death rates than the general population. To determine whether this trend has changed over time, researchers evaluated mortality data from a cohort of more than 60,000 homeless-experienced individuals over a 16-year period. Findings revealed that the gap in death rates between the homeless cohort and the general population widened over time. The primary drivers of this widening gap were the disproportionate rise in drug overdose deaths and chronic lung disease-related deaths in the homeless cohort. This research underscores the urgent need for policies that prioritize housing access and sustainability and interventions that address the unique needs of homeless-experienced individuals to address this long-standing mortality disparity.

(Summary submitted by Danielle R. Fine, MD, MSC, Department of Medicine)

Clinical trials are the gold standard for advancing evidence-based medicine and the participation of diverse populations helps ensure research is representative of and applicable to all patients. In our study, the reporting of race and ethnicity information in clinical trials enrolling children under 18 years old improved from 2007-2018, but Black, Hispanic, and Asian children were underrepresented relative to the U.S. population. To address these gaps, policymakers, researchers, and institutions should develop strategies focused on the recruitment and retention of marginalized communities.

(Summary submitted by Ryan Brewster, MD, Boston Children's Hospital)

Patients value time spent at home, but few outcome measures directly capture this patient-centered priority. In the present study, we examined the association between days alive and at home at day 90 (DAAH90) and clinical outcomes among patients admitted to the intensive care unit (ICU). We found that DAAH90 robustly reflects the burden of ICU admission and captures the long-term consequences of critical illness for functional status, quality of life, and survival. These findings suggest that DAAH90 could be used as a patient-centered outcome measure in future trials of critically ill patients.

(Summary submitted by Shaurya Taran, MD, Department of Neurology)

Racial/ethnic minority individuals face barriers to entry and advancement in surgery. However, no large-scale investigations of the operative experience of racial/ethnic minority trainees exist. In our multi-institutional study of 1343 general surgery residents who graduated between 2010-2020, Black residents performed significantly fewer surgical cases than White residents, particularly during the initial years of training. This educational disparity persisted over the previous decade and was not observed among other underrepresented groups. Decreased exposure to operative learning opportunities may impede the early professional development of Black surgeons. Our research highlights the critical need for systemic educational interventions to support underrepresented surgical residents and promote positive culture change.

(Summary submitted by Chukwuma N. Eruchalu, MD, Department of Surgery)

Clumps of a protein called TDP-43 form in affected neurons of patients with different neurodegenerative diseases leading to paralysis or dementia. We found that disruption of TDP-43 in these neurons leads to the loss of Stathmin-2, a protein essential for the ability of neurons to regenerate after injury and to keep their connection with muscles to control movements. We have identified a gene therapy approach to restore expression of Stahmin-2 in affected neurons that represents a promising strategy for therapeutic development in patients with neurodegenerative conditions.

(Summary submitted by Clotilde Lagier-Tourenne, MD, PhD, Department of Neurology)

Ghrelin is a hormone that promotes weight gain in rodent models but naturalistic studies of humans older than infants have consistently demonstrated a lack of association between ghrelin and weight trajectory. We show for the first time in humans older than infants, that there is a robust association between elevated levels of circulating ghrelin and prospective weight gain in girls and women with anorexia nervosa (AN). This novel discovery expands our understanding of body weight regulation in humans, which could potentially contribute to treatment development for AN, an illness with one of the highest premature mortality rates in psychiatry with a complete lack of FDA-approved treatments.

(Summary submitted by Youngjung Rachel Kim, MD, PhD, Department of Psychiatry)

Previous studies have found associations between other infections during pregnancy and increased risk of neurodevelopmental disorders in children, such as autism spectrum disorder, but it’s unclear if such a link exists with SARS‐CoV‐2 infection during pregnancy. To investigate, scientists examined electronic health records for 18,355 live births during the COVID-19 pandemic, including 883 (4.8%) to individuals with SARS‐CoV‐2 positivity during pregnancy. Of the 883 SARS‐CoV‐2–exposed children, 26 (3.0%) received a neurodevelopmental diagnosis during the first 12 months of life. Among the SARS‐CoV‐2–unexposed offspring, 317 (1.8%) received such a diagnosis. After accounting for race, ethnicity, insurance status, hospital type (academic center vs. community), maternal age, and preterm status, maternal SARS‐CoV‐2 positivity was associated with a nearly two-fold higher odds of a neurodevelopmental diagnosis at 12 months of age among male children. Maternal SARS‐CoV‐2 positivity was not linked with a higher risk in female children, however.

Storing and sharing digital scans of whole-slide microscopy images, either for research or practice, is currently difficult due to a lack of data standardization. In collaboration with BWH and the NCI’s imaging data commons, we developed Slim, a modern web application to view and annotate slide microscopy images using the internationally accepted standard for medial digital imaging, DICOM. DICOM has its roots in radiology imaging but has made great strides in supporting pathology workflows in recent years. Slim requires no server-side image processing and thus allows users to connect to any number of DICOMweb-compliant vendor-neutral imaging archives on-premises or in the cloud. Slim is open-source and available at https://github.com/ImagingDataCommons/slim

(Summary submitted by Christopher Gorman, PhD, Mass General Cancer Center)

Schwannomas are common sporadic tumors and hallmarks of familial neurofibromatosis type 2 (NF2) that form around spinal and cranial nerves. Unlike most tumors schwannomas are caused by inactivation of a single gene - the NF2 tumor suppressor gene. Despite this genetic uniformity, schwannomas exhibit variable clinical features and therapeutic sensitivities. Our studies link heterogeneity to unstable polarity and aberrant programs of ErbB production and signaling exhibited by NF2-mutant Schwann cells. We validated biomarkers of this mechanism in human and mouse schwannomas and developed quantitative imaging to map schwannoma heterogeneity. Our work highlights the broad importance of intrinsic mechanisms of tumor heterogeneity.

(Summary submitted by Andrea I. McClatchey, PhD, Center for Cancer Research, Department of Pathology)

Increased left ventricular mass (LVM) is a major risk factor for heart disease and sudden cardiac death. The mechanisms of increased LVM are not fully established, but it is believed to have a strong heritable component. We applied artificial intelligence to cardiac magnetic resonance images from 40,000 UK Biobank participants to estimate LVM. We then performed genome-wide association analyses and identified 12 genetic loci associated with LVM. Implicated genes affect cardiac contractility or neurohormonal regulation, and some have been associated with rare inherited heart conditions. A genetic risk score demonstrated associations between genetically-determined LVM and future heart disease.

(Summary submitted by Shaan Khurshid, MD, Cardiology Division, Department of Medicine)

Investigators found that the immune response to a virus that is ubiquitously present in human tissues can detect and eliminate aging cells in the skin. The research discoveries enable a new therapeutic approach to eliminate aging cells by boosting the anti-viral immune response.

(Summary submitted by Shawn Demehri, MD, Department of Dermatology)

Press Releases

Researchers Bioengineer an Endocrine Pancreas for Type 1 Diabetes
Featuring Hong Ping Deng, MD, MSc, Ji Lei, MD, MBA, MSc and Co-author James F. Markmann, MD, PhD

Transplanting donor islet tissue to a bioengineered omentum—the fatty tissue that drapes from the stomach over the intestines—normalized blood glucose levels in nonhuman primates with type 1 diabetes. The findings reveal a promising alternative strategy for islet transplantation when treating type 1 diabetes, particularly in the field of stem cell–based therapy.

Artificial Intelligence Approach May Help Detect Alzheimer's Disease from Routine Brain Imaging Tests
Featuring Matthew Leming, PhD

Researchers have developed and validated a deep learning–based method to detect Alzheimer’s disease based on routinely collected clinical brain images. The tool may help clinicians identify patients who would benefit from treatment.

Risk of Thrombotic Events Should Not Exclude Transgender People from Receiving Hormone Therapy, According to New Guidance
Featuring Robbie Goldstein, MD, PhD

Clinical evidence shows that transgender women who develop venous thromboembolism while on feminizing hormone therapy can be safely treated and managed with anticoagulation therapy. The risk of discontinuing gender affirming hormone therapy for transgender patients can be greater than the minimal risk for thrombotic events while on therapy.

Genetic and Socioeconomic Factors Interact to Affect Risk of Type 2 Diabetes and Obesity
Featuring Sara Cromer, MD, and Miriam Udler, MD, PhD

In analyses of genetic and area-level socioeconomic data for more than 260,000 individuals, researchers found an additive effect of genetic and socioeconomic risk on the prevalence of obesity and type 2 diabetes. The study quantified the genetic and socioeconomic risk associated with these conditions as well as the combined effect of these risk factors at a population level.

Mass General Researchers Discover the Role of Intestinal Fibrosis in Inflammatory Bowel Disease
Featuring Nima Saeidi, PhD, Shijie He, PhD, and Peng Lei, PhD

Traditionally considered a bystander of inflammation, with negligible involvement in disease pathogenesis, new research now shows that fibrosis has a direct bearing on disease progression in IBD.

New Insights by Mass General on the Molecular Mechanism of Hydrocephalus Could Lead to the First-ever Non-surgical Treatment
Featuring Kristopher Kahle, MD, PhD

Researchers have learned that the same molecular pathway is involved in both the infectious and hemorrhagic forms of acquired hydrocephalus, a life-threatening disease that triggers a massive neuroinflammatory response and swelling of the ventricles of the brain. An FDA-approved immune suppressant drug, rapamycin, was shown to block inflammation in the ventricles and prevent development of acquired hydrocephalus in animal models.

New Insights into How Patient Factors and COVID-19 Infection Affect Antibody Responses in People with HIV
Featuring Steven Grinspoon, MD

Researchers have examined how patient characteristics and COVID-19 infection may affect the antibody responses of people with HIV—including responses against SARS-CoV-2 proteins as well as proteins from other viruses. The findings may help explain why some people with HIV experience severe symptoms if infected with SARS‐CoV‐2.

Normalizing Tumor Blood Vessels May Improve Immunotherapy Against Brain Cancer
Featuring Rakesh K. Jain, PhD

A type of immune therapy called chimeric antigen receptor (CAR)-T cell therapy has shown limited efficacy against glioblastoma and other solid tumors, but researchers have found that this might be remedied by normalizing glioblastoma blood vessels using an antibody that blocks vascular endothelial. In mice with glioblastoma, treatment with the antibody improved the infiltration of CAR-T cells as well as the body’s own T cells into tumors, inhibited tumor growth, and prolonged survival.

Researchers Uncover a Protein Deficiency in Neurons of Patients with Neurodegenerative Diseases That Could Be Targeted by New Gene Therapy Approach
Featuring Clotilde Lagier-Tourenne, MD, PhD

Clumps of proteins form in affected neurons of patients with different neurodegenerative diseases, leading to paralysis or dementia. Researchers discovered that a protein called Stathmin-2 is lost in these neurons, which prevents them from regenerating after injury and disrupts their connection with the muscles to control movements. The team also identified a gene therapy approach to restores expression of Stathmin-2 in affected neurons, representing a promising new therapeutic approach for patients with neurodegenerative diseases.

Collaborative Research Team is the First to Link Parkinson’s Disease to Red Pigment in the Brain
Featuring Xiqun Chen, MD, PhD

Brain samples of patients with Parkinson’s disease have more red/yellow pigment compared to healthy controls. By contrast, black/brown pigment levels were much lower in Parkinson’s patients. The study is the first to link Parkinson’s disease to red pigment in the brain, adding to the team’s earlier findings linking the disease to the lighter pigment in hair/skin.

SARS‐CoV‐2 Infection During Pregnancy Linked to Higher Risk of Neurodevelopmental Disorders in Male Infants
Featuring Andrea Edlow, MD and Roy Perlis, MD

In an analysis of electronic health records for 18,355 live births during the COVID-19 pandemic, maternal SARS‐CoV‐2 positivity during pregnancy was associated with nearly two-fold higher odds of a neurodevelopmental diagnosis at 12 months of age among male children. Maternal SARS‐CoV‐2 positivity was not linked with a higher risk of neurodevelopmental diagnosis at 12 months of age in female children.

Boosting the Body’s Anti-viral Immune Response May Eliminate Aging Cells
Featuring Shawn Demehri, MD, PhD

Aging cells express a protein that is produced by human cytomegalovirus and is targeted by certain immune cells in the body. Harnessing the immune response to this protein could have multiple health benefits during aging.

Blog Posts

Public Health 101: Understanding the Difference Between Public Health and Public Health Research

How public health and public health researchers work together to identify and solve problems that impact the health of communities.

Benchmarks: Mass General Research News and Notes for March 3, 2023

Your weekly dose of Mass General research news. Disparities in healthcare, job loss due to a rare disease, the tweets of the week & more.

Humans of MGRI: Emily King

Emily King's research focus is on developing and optimizing gene editing proteins for therapeutic and research applications.

Through the Magnifying Glass: The Dekel Lab and the Psychiatry of Childbirth

A close-up look at the Dekel Lab, which is working to understand more about the psychiatry of childbirth

The Science of Tea: What Research Tells Us about the Benefits of an Ancestral Tradition
Featuring Umadevi Naidoo, MD

Mass General clinician-researcher Uma Naidoo, MD discusses the benefits of tea, according to science.

Addressing Racial, Ethnic and Language Disparities in Care Management
Featuring Priscilla Wang, MD, MPH

Priscilla Wang, MD, MPH, and her team studied whether race, ethnicity and language are associated with patient entry and service intensity within a large care management program, from a structural health point of view.

Benchmarks: Mass General Research News and Notes for March 10, 2023

An AI model enables Alzheimer's disease detection from brain MRIs, smartphone apps to help with mental health and lots more.

Footnotes in Science: Q&A with Erin C Dunn, ScD, MPH

Mass General Erin Dunn, ScD, MPH, discusses her recent research looking at the connections between socioeconomic factors and mental health.

The Next Generation of the Opioid Epidemic: Youth Polysubstance Users
Featuring Scott Hadland, MD, MPH, MS

A closer look at how the opioid epidemic is impacting the youngest generation of Americans, and how Scott Hadland, MD, MPH, MS, Chief of Adolescent and Young Adult Medicine at Mass General for Children wants to change that.

It’s Brain Awareness Week! Here Are Three Super-Cool Studies Involving Brain Imaging
Featuring Gary Boas

As part of Brain Awareness Week, we are highlighting three innovative Mass General brain imaging studies.

Benchmarks: Mass General Research News and Notes for Friday, March 17

Benchmarks is your weekly dose of news and notes about the Massachusetts General Hospital research community. With over 9,500 investigators, there’s more news than we can cover each week. Here are a few highlights.

MGH Clinical Research Coordinator, Who Moonlights as a Runner, Is Fundraising for MGfC
Featuring Erin Morrissey

Erin Morrissey is running the Boston Marathon to support Mass General for Children and pay back the kindness she received as a patient.

Footnotes in Science: Q&A with Amanda Lans MD, MS

In this Q&A, we pick the brain of Dr. Lans about her latest research article, Health Literacy in Orthopedic Surgery: A Systematic Review".

Benchmarks: Mass General Research News and Notes for March 31, 2023

New research to help veterans with PTSD, using mobile technology to predict and prevent suicide attempts, the tweets of the week & more.

Research Spotlights

Using Extracellular Vesicles for Earlier Detection of Bile Duct Cancer
Featuring Hyungsoon Im, PhD

Researchers found that molecular analysis of extracellular vesicles (EVs) in human bile samples could accurately detect patients with cholangiocarcinoma from patients with other benign or inflammatory conditions.

Elucidating the Pathogenesis of Cerebral Arachnoid Cysts (ACs)
Featuring Kristopher Kahle, MD, PhD

Researchers performed an integrated analysis of patient-parent exomes and other data and found damaging de novo variants were highly enriched in patients with ACs compared to healthy individuals.

Disparities in the Initiation of Guideline-Recommended Diabetes Medications
Featuring Sara Cromer, MD

Researchers wanted to know if the current guidelines recommending the use of these drugs in patients with type 2 diabetes and cardiovascular or renal indications were being followed, and if there were sex, race/ethnicity, or socioeconomic status-based disparities in their use.

A Parathyroid Hormone/Salt-Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation and Organismal Calcium Homeostasis
Featuring Marc Wein, MD, PhD

Researchers identified a key role for salt-inducible kinases in regulating vitamin D activation downstream of parathyroid hormone (PTH) action. We also defined the subset of cells within the proximal tubule where PTH triggers vitamin D activation.

The Mass General Difference

Conditions & Treatments

Patients & Visitors

Research & Innovation

Mass General
Research Institute

Snapshot of Science for March 2023