Unveiling a Potential Novel Antiviral Immunotherapy
Evasion of NKG2D-mediated Cytotoxic Immunity by Sarbecoviruses
Hartmann JA, Cardoso MR, Talarico MCR, Kenney DJ, Leone MR [et al.], Garcia-Beltran WF
Published in Cell on 4/22/2024 | *Summary available 

Understanding Durvalumab Benefits for Non-small Cell Lung Cancer
Durvalumab After Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer
Mooradian MJ, Cai L, Wang A, Qiao Y, Chander P, Whitaker RM
Published in JAMA Network Open on 4/22/2024 

Creating a Tool for Genotype and Phenotype Outcome Modeling
Joint Genotypic and Phenotypic Outcome Modeling Improves Base Editing Variant Effect Quantification
Ryu J, Barkal S, Yu T, Jankowiak M, Zhou Y [et al.], Pinello L
Published in  Nature Genetics on 4/24/2024 | *Summary available 

Investigating Mutations in the Cell Division Process
Single-cell Analysis Reveals Context-dependent, Cell-level Selection of mtDNA
Kotrys AV, Durham TJ, Guo XA, Vantaku VR, Parangi S, Mootha VK
Published in  Nature on 4/24/2024 

Neuropsychiatric Outcomes of Children with Prenatal Opioid Exposure
Prenatal Opioid Exposure and Subsequent Risk of Neuropsychiatric Disorders in Children: Nationwide Birth Cohort Study in South Korea
Kang J, Kim HJ, Kim T, Lee H, Kim M [et al.], Solmi M
Published in  BMJ  on 4/24/2024 | *Summary available 

Investigating How Our Brain Processes Sounds When Visual Stimuli Are Present Investigating How Our Brain Processes Sounds when Visual Stimuli are Present
Neuronal Modeling of Cross-Sensory Visual Evoked Magnetoencephalography Responses in the Auditory Cortex
Lankinen K, Ahveninen J, Jas M, Raij T, Ahlfors SP
Published in  Journal of Neuroscience on 4/24/2024 

Amino Acids Role in Vaccination Against the Flu Amino Acids Role in Vaccination against the Flu
Eliciting a Single Amino Acid Change by Vaccination Generates Antibody Protection Against Group 1 and Group 2 Influenza A Viruses
Ray R, Nait Mohamed FA, Maurer DP, Huang J, Alpay BA [et al.], Lingwood D
Published in  Immunity  on 4/25/2024 | *Summary available 

How the Fight-or-flight Midbrain Structure Plays a Role in Everyday Tasks
7-Tesla Evidence for Columnar and Rostral-caudal Organization of the Human Periaqueductal Gray Response in the Absence of Threat: A Working Memory Study
Fischbach AK, Satpute AB, Quigley K, Kragel PA, Chen D [et al.], Theriault JE
Published in Journal of Neuroscience on 4/25/2024 | *Summary available 

Diverticulitis and the Gut Microbiome
Gut Microbiome Composition and Metabolic Activity in Women with Diverticulitis
Ma W, Wang Y, Nguyen LH, Mehta RS, Ha J [et al.], Chan AT
Published in Nature Communications on 4/29/2024 | *Summary available 

Investigating Vulnerability of Cancer Cells: Uracil as a Source of DNA Replication Stress
Unprocessed Genomic Uracil as a Source of DNA Replication Stress in Cancer Cells
Saxena S, Nabel CS, Seay TW, Patel PS, Kawale AS [et al.], Zou L
Published in Molecular Cell on 4/29/2024 | *Summary available 

Measuring Brain Signals with Single-Vessel fMRI
High Spatiotemporal Resolution Radial Encoding Single-Vessel fMRI
Jiang Y, Pais-Roldán P, Pohmann R, Yu X
Published in Advanced Science on 4/30/2024 | *Summary available 

VICR Also Occurs in C. elegans Body Muscless
Voltage-induced Calcium Release in Caenorhabditis elegans Body Muscles
Gao L, Ardiel E, Nurrish S, Kaplan JM
Published in  PNAS on 4/30/2024 

Clonal Hematopoeisis and Atrial Fibrillation
Clonal Hematopoiesis of Indeterminate Potential With Loss of Tet2 Enhances Risk for Atrial Fibrillation Through Nlrp3 Inflammasome Activation
Lin AE, Bapat AC, Xiao L, Niroula A, Ye J [et al.], Ebert BL
Published in Circulation on 4/30/2024 | *Summary available 

Anesthesia's Effects on PET Imaging
Common Anesthetic Used in preclinical PET Imaging Inhibits Metabolism of the PET Tracer [18F]3F4AP
Ramos-Torres K, Sun Y, Takahashi K, Zhou YP, Brugarolas P
Published in  Journal of Neurochemistry  on 5/1/2024 | *Summary available | Research Spotlight 

Brain Imaging Study Reveals Connections Critical to Human Consciousness
Multimodal MRI Reveals Brainstem Connections that Sustain Wakefulness in Human Consciousness
Edlow BL, Olchanyi M, Freeman HJ, Li J, Maffei C [et al.], Kinney HC
Published in  Science Translational Medicine on 5/1/2024 | *Summary available | Press Release 

Hillocks: A New Airway Barrier Structure
Airway Hillocks Are Injury-resistant Reservoirs of Unique Plastic Stem Cells
Lin B, Shah VS, Chernoff C, Sun J, Shipkovenska GG [et al.], Rajagopal J
Published in  Nature on 5/1/2024 | *Summary available 

Combination Therapy of Navitoclax and Trametinib
Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors
Corcoran RB, Do KT, Kim JE, Cleary JM, Parikh AR [et al.], Shapiro GI
Published in  Clinical Cancer Research on 5/1/2024 

Improving CAR T Therapy for Pancreatic Cancer
Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma
Wehrli M, Guinn S, Birocchi F, Kuo A, Sun Y [et al.], Maus MV
Published in Clinical Cancer Research on 5/1/2024 | *Summary available 

AMERK Serostatus as Predictor of Merkel Cell Carcinoma Outcomes
The Prognostic Value of the Merkel Cell Polyomavirus Serum Antibody Test: A Dual Institutional Observational Study
Miller DM, Shalhout SZ, Wright KM, Miller MA, Kaufman HL [et al.], Thakuria M
Published in  Cancer on 5/2/2024 | *Summary available 

Post-Procedure cfDNA Detection Status and Colorectal Cancer Recurrence
Minimal Residual Disease using a Plasma-Only Circulating Tumor DNA Assay to Predict Recurrence of Metastatic Colorectal Cancer Following Curative Intent Treatment
Parikh AR, Chee BH, Tsai J, Rich TA, Price KS [et al.], Atreya CE
Published in Clinical Cancer Research on 5/2/2024 | *Summary available 

Assessing the Sensitivity and Yield of Inpatient Diagnostic Algorithms for Pulmonary Tuberculosis in a Low-Prevalence Setting
Second Time’s the Charm? Assessing the Sensitivity and Yield of Inpatient Diagnostic Algorithms for Pulmonary Tuberculosis in a Low-prevalence Setting
Dugdale CM, Zachary KC, McEvoy DS, Branda JA, Courtney A [et al.], Shenoy ES
Published in  Open Forum Infectious Diseases on 5/3/2024 | *Summary available | Research Spotlight 

Clinical Trial Shows that Cytisinicline Can Help People Quit Vaping
Cytisinicline for Vaping Cessation in Adults Using Nicotine E-Cigarettes: The ORCA-V1 Randomized Clinical Trial
Rigotti NA, Benowitz NL, Prochaska JJ, Cain DF, Ball J [et al.], Jacobs C
Published in  JAMA Internal Medicine on 5/6/2024 | *Summary available | Press Release 

Proof-of-Mechanism and Clinical Feasibility of Sacituzumab Govitecan
Antibody Drug Conjugate Sacituzumab Govitecan Enables A Sequential TOP1/PARP Inhibitor Cancer Therapy Strategy in Breast Cancer Patients
Bardia A, Sun S, Thimmiah N, Coates JT, Wu B [et al.], Ellisen LW
Published in Clinical Cancer Research on 5/6/2024 | *Summary available 

Neural States of Cannabis Impairment
Intoxication Due to Δ9-tetrahydrocannabinol is Characterized by Disrupted Prefrontal Cortex Activity
Karunakaran KD, Pascale M, Ozana N, Potter K, Pachas GN, Evins AE, Gilman JM
Published in  Neuropsychopharmacology on 5/7/2024 | *Summary available | Press Release 

Oncogenic FGFR2 Signaling in Intrahepatic Cholangiocarcinoma
FGFR Inhibition Blocks NF-ĸB-dependent Glucose Metabolism and Confers Metabolic Vulnerabilities in Cholangiocarcinoma
Zhen Y, Liu K, Shi L, Shah S, Xu Q [et al.], Bardeesy N
Published in  Nature Communications on 5/7/2024 | *Summary available 

CDK-Rb Pathway Blockade in IDH-Mutant Glioma
CDKN2A/B Homozygous Deletion Sensitizes IDH-mutant Glioma to CDK4/6 Inhibition
Nasser AM, Melamed L, Wetzel E, Chang CC, Nagashima H [et al.], Miller JJ
Published in Clinical Cancer Research on 5/8/2024 | *Summary available 

Previously Uninvestigated Elastic and Viscous Response in Tissue
Laser Speckle Rheological Microscopy Reveals Wideband Viscoelastic Spectra of Biological Tissues
Leartprapun N, Zeng Z, Hajjarian Z, Bossuyt V, Nadkarni SK
Published in  Science Advances on 5/8/2024 | *Summary available 

A Better Understanding of Immune Checkpoint Inhibitor-Related Colitis
Single-cell Transcriptomic Analyses Reveal Distinct Immune Cell Contributions to Epithelial Barrier Dysfunction in Checkpoint Inhibitor Colitis
Thomas MF, Slowikowski K, Manakongtreecheep K, Sen P, Samanta N [et al.], Villani AC
Published in  Nature Medicine on 5/9/2024 | *Summary available | Research Spotlight 

Optimizing the Dosing of Lurbinectedin for Leiomyosacroma
Safety And Efficacy Of Combination Lurbinectedin Plus Doxorubicin From A Phase 1b Trial In Patients With Advanced/Metastatic Soft Tissue Sarcoma
Cote GM, Haddox CL, Choy E, Merriam PA, Mazzola E [et al.], George S
Published in Clinical Cancer Research on 5/9/2024 | *Summary available 

Candidate Risk Factors for Hydroxycloroquine Retinopathy
Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes
Jorge AM, Melles RB, Marmor MF, Zhou B, Zhang Y, Choi HK
Published in  JAMA Network Open on 5/9/2024 

Differences in Live Expectancy for Youth with HIV
Projected Life Expectancy for Adolescents With HIV in the US
Neilan AM, Ufio OL, Brenner IR, Flanagan CF, Shebl FM [et al.], Patel K
Published in  JAMA Health Forum on 5/10/2024 | *Summary available | Press Release 

The Genetic Basis by Which Host Immunity Impacts HIV Outcomes
Polymorphic Residues in HLA-B that Mediate HIV Control Distinctly Modulate Peptide Interactions with Both TCR and KIR Molecules
Tano-Menka R, Singh NK, Muzhingi I, Li X, Mandanas MV [et al.], Gaiha GD
Published in  Structure on 5/10/2024 | *Summary available 

Age Affects the Priming of T Cells in the Microenvironment
The Aged Tumor Microenvironment Limits T Cell Control of Cancer
Chen ACY, Jaiswal S, Martinez D, Yerinde C, Ji K [et al.], Sen DR
Published in Nature Immunology  on 5/14/2024 | *Summary available | Research Spotlight 

Polygenic Screenings Have High Public Approval and Interest
Public Attitudes, Interests, and Concerns Regarding Polygenic Embryo Screening
Furrer RA, Barlevy D, Pereira S, Carmi S, Lencz T, Lázaro-Muñoz G
Published in  JAMA Network Open  on 5/14/2024 | *Summary available 

Supporting Research of Populations with Diverse Ancestry
A Harmonized Public Resource of Deeply Sequenced Diverse Human Genomes
Koenig Z, Yohannes MT, Nkambule LL, Zhao X, Goodrich JK [et al.], Martin AR
Published in  Genome Research on 5/15/2024 | *Summary available  

PRC2 Preferentially Binds Folded rG4s
G-quadruplex Folding in Xist RNA Antagonizes PRC2 Activity for Stepwise Regulation of X Chromosome Inactivation
Lee YW, Weissbein U, Blum R, Lee JT
Published in  Molecular Cell on 5/16/2024 | *Summary available 

Predicting Chemotherapy Response in Pancreatic Cancer
Allysine-Targeted Molecular MRI Enables Early Prediction of Chemotherapy Response in Pancreatic Cancer
Ma H, Esfahani SA, Krishna S, Ataeinia B, Zhou IY [et al.], Caravan P
Published in  Cancer Research on 5/17/2024 | *Summary available 

Higher Consumption of Ultra-Processed Foods Leads to Worse Brain Health
Associations Between Ultra-Processed Food Consumption and Adverse Brain Health Outcomes
Bhave VM, Oladele CR, Ament Z, Kijpaisalratana N, Jones AC [et al.], Kimberly WT
Published in  Neurology  on 5/22/2024 | *Summary available | Press Release 

Statin Therapy May Prevent Cancer by Blocking Inflammatory Protein
Statin Prevents Cancer Development in Chronic Inflammation by Blocking Interleukin 33 Expression
Park JH, Mortaja M, Son HG, Zhao X, Sloat LM [et al.], Demehri S
Published in  Nature Communications on 5/30/2024 | Press Release 

Unveiling a Potential Novel Antiviral Immunotherapy
Evasion of NKG2D-mediated Cytotoxic Immunity by Sarbecoviruses
Hartmann JA, Cardoso MR, Talarico MCR, Kenney DJ, Leone MR [et al.], Garcia-Beltran WF
Published in Cell on 4/22/2024 

In this study, we discovered a key strategy SARS-CoV-2 uses to evade immune detection, particularly by natural killer (NK) cells. The virus manipulates the cells it infects to reduce visibility by a crucial immune receptor, NKG2D, on NK cells. This makes it harder for the immune system to recognize and destroy these cells. We found that a monoclonal antibody, originally developed for cancer therapy, can block this process, boosting the immune response against SARS-CoV-2 and the broader family of viruses it belongs to. This may enhance the effectiveness of existing treatments for COVID-19 and future viral outbreaks. 

(Summary submitted by Wilfredo F Garcia-Beltran, MD, PhD, Ragon Institute of Mass General, MIT and Harvard, Department of Pathology) 

Creating a Tool for Genotype and Phenotype Outcome Modeling
Joint Genotypic and Phenotypic Outcome Modeling Improves Base Editing Variant Effect Quantification
Ryu J, Barkal S, Yu T, Jankowiak M, Zhou Y [et al.], Pinello L
Published in  Nature Genetics on 4/24/2024 

CRISPR base editing technology allows studying how specific DNA variants alter cellular function. While base editing can be used in high-throughput screens to study thousands of variants in a single experiment, the heterogeneous base editing outcome has hindered assessing the impact of each introduced variant. We tackle the challenge by developing an integrated experimental-computational pipeline that simultaneously measures the cellular response and the base editing outcome, allowing a more accurate estimation of variant impacts over existing methods. We use this approach to assess the impact on cholesterol levels of thousands of variants which might impact patient risk for cardiovascular disease. 

(Summary submitted by Jayoung Ryu, HMS Bioinformatics & Integrative Genomics PhD Program) 

Neuropsychiatric Outcomes of Children with Prenatal Opioid Exposure
Prenatal Opioid Exposure and Subsequent Risk of Neuropsychiatric Disorders in Children: Nationwide Birth Cohort Study in South Korea
Kang J, Kim HJ, Kim T, Lee H, Kim M [et al.], Solmi M
Published in  BMJ on 4/24/2024 

Previous studies have shown inconsistent results regarding the association between maternal opioid use and neuropsychiatric disorders in children. This large-scale, population-based, birth cohort study of 3,251,594 infants in Korea aimed to investigate this relationship. Opioid use during pregnancy was not associated with a substantial increase in the risk of neuropsychiatric disorders in the offspring, particularly in sibling-controlled analyses. However, the risk increased with high opioid doses, multiple opioid use, longer exposure, and use during early pregnancy, with effects specific to certain neuropsychiatric disorders. These results underscore the need for cautious opioid prescribing during pregnancy and further research for more definitive guidelines. 

(Summary submitted by Jiseung Kang, PhD, Department of Anesthesia, Critical Care and Pain Medicine) 

Amino Acids Role in Vaccination against the Flu
Eliciting a Single Amino Acid Change by Vaccination Generates Antibody Protection Against Group 1 and Group 2 Influenza A Viruses
Ray R, Nait Mohamed FA, Maurer DP, Huang J, Alpay BA [et al.], Lingwood D
Published in  Immunity on 4/25/2024 

Differences in viral glycosylation normally prevents antibodies from broadly engaging an otherwise conserved vaccine target on the surface glycoprotein of flu. In this study, we deploy rationally designed nanoparticle immunogens to elicit pan-protecting antibodies within a humanized vaccine model that we engineered to mimic the B cell repertoire of humans. These antibodies ‘solve’ the glycosylation problem by acquiring a single amino acid mutation or ‘switch’ that tilts the immunoglobulin to accommodate the viral glycan diversity. Collectively our study shows that exceptionally broad influenza immunity can be elicited by via an exceptionally simple pathway of human antibody development. 

(Summary submitted by Daniel Lingwood, PhD, Infectious Disease Unit, Department of Medicine) 

How the Fight-or-flight Midbrain Structure Plays a Role in Everyday Tasks
7-Tesla Evidence for Columnar and Rostral-caudal Organization of the Human Periaqueductal Gray Response in the Absence of Threat: A Working Memory Study
Fischbach AK, Satpute AB, Quigley K, Kragel PA, Chen D [et al.], Theriault JE
Published in  Journal of Neuroscience on 4/25/2024 

The periaqueductal gray (PAG) is a small midbrain structure, traditionally though to house fight-or-flight “survival circuits”. This reputation leads most studies to test PAG function in threatening contexts (e.g., during electric shock), but there is reason to think PAG plays a role outside of threat. We used ultra-high-resolution neuroimaging to examine PAG response as people performed a working memory task—about as easy as remembering a phone number—and we saw spatial patterns of PAG activity that were very similar to patterns seen in fight-or-flight situations. This result should make us reexamine our preconceptions about the role of PAG in real-world behavior. 

(Summary submitted by Jordan E Theriault, PhD, Martinos Center for Biomedical Imaging, Department of Radiology) 

Diverticulitis and the Gut Microbiome
Gut Microbiome Composition and Metabolic Activity in Women with Diverticulitis
Ma W, Wang Y, Nguyen LH, Mehta RS, Ha J [et al.], Chan AT
Published in  Nature Communications on 4/29/2024 

Diverticulitis is a common digestive disorder that often results in hospitalizations and emergency room visits. However, the exact causes of this disease are not well understood. Using shotgun metagenomics and untargeted metabolomics, we performed a comprehensive examination of the composition and metabolic profiles of the stool microbiomes from individuals with diverticulitis and compared them to those without the condition. We revealed disturbances of microbial and metabolic signatures, particularly those with inflammatory properties, along with co-occurring microbe-metabolite associations relevant to diverticulitis. These findings offer novel insights into the disease pathogenesis, supporting the potential of microbiome-based diagnostic and therapeutic strategies. 

(Summary submitted by Wenjie Ma, DSc, Division of Gastroenterology, Department of Medicine) 

Investigating Vulnerability of Cancer Cells: Uracil as a Source of DNA Replication Stress
Unprocessed Genomic Uracil as a Source of DNA Replication Stress in Cancer Cells
Saxena S, Nabel CS, Seay TW, Patel PS, Kawale AS [et al.], Zou L
Published in  Molecular Cell on 4/29/2024 

A major breakthrough in cancer research reveals a vulnerability in cancer cells! We found that uracil, a common DNA alteration, slows down the copying of DNA and creates gaps in the genome. To fix these gaps, cancer cells rely on a protein called ATR. By inhibiting ATR, we can prevent these gaps from being repaired, generating more DNA damage in cancer cells. Interestingly, some cancers try to prevent uracil buildup through a protein called UNG2. These cancers with high UNG2 are especially vulnerable to a treatment that combines ATR inhibition with drugs that increase uracil levels. This discovery presents a promising new avenue for targeted cancer therapy. 

(Summary submitted by Sneha Saxena, PhD, Krantz Family Center for Cancer Research, Mass General Cancer Center) 

Measuring Brain Signals with Single-Vessel fMRI
High Spatiotemporal Resolution Radial Encoding Single-Vessel fMRI
Jiang Y, Pais-Roldán P, Pohmann R, Yu X
Published in  Advanced Science on 4/30/2024 

To achieve the high spatial resolution for functional magnetic resonance imaging (fMRI), we developed a method to measure fMRI signals from individual vessels penetrating the rat somatosensory cortex using a radial encoding MRI scheme. Unlike conventional Cartesian acquisition, our approach offers spatial and temporal flexibility by defining arbitrary numbers of azimuthal projections. We demonstrated vessel-specific functional mapping with an in-plane resolution of 50x50 µm and a sampling rate of 1 to 2 Hz. Our method enabled the direct characterization of fMRI signals from vessel and peri-vessel voxels, providing the opportunity to distinguish the intravascular and extravascular effect. 

(Summary submitted by Yuanyuan Jiang, PhD, Department of Radiology) 

Clonal Hematopoeisis and Atrial Fibrillation
Clonal Hematopoiesis of Indeterminate Potential With Loss of Tet2 Enhances Risk for Atrial Fibrillation Through Nlrp3 Inflammasome Activation
Lin AE, Bapat AC, Xiao L, Niroula A, Ye J [et al.], Ebert BL
Published in Circulation on 4/30/2024 

Clonal hematopoeisis of indeterminate potential (CHIP) is an age-associated phenomenon resulting from somatic mutations in hematopoietic stem cells. CHIP is associated with atherosclerotic heart disease and heart failure; this study investigated its association with atrial fibrillation (AF). AF is a common heart rhythm disorder that increases in prevalence with advancing age. Human genetic data from the UK Biobank was analyzed to identify an associated between certain CHIP mutations and AF. This finding then was further corroborated using mouse models, recognizing a critical role for the NLRP3 inflammasome. This study adds to the growing evidence linking inflammation and AF. 

(Summary submitted by Aneesh Bapat, MD, Cardiology Division, Department of Medicine) 

Anesthesia's Effects on PET Imaging
Common Anesthetic Used in preclinical PET Imaging Inhibits Metabolism of the PET Tracer [18F]3F4AP
Ramos-Torres K, Sun Y, Takahashi K, Zhou YP, Brugarolas P
Published in  Journal of Neurochemistry on 5/1/2024 | Research Spotlight 

PET tracers are radioactive molecules that are injected into a subject to image disease proceses using a PET scanner. Before using a new tracer in humans it is important to test it in laboratory animals like mice or monkeys to make sure that it works as expected. Because animals tend not to stay still during a PET scan, animals are usually scanned anesthetized. We found that a tracer that we previously developed and is now in human studies at MGH showed very different results in animals and humans and we were able to show that the differences were due to anesthesia. 

(Summary submitted by Pedro Brugarolas, PhD, Gordon Center for Medical Imaging, Department of Radiology) 

Brain Imaging Study Reveals Connections Critical to Human Consciousness
Multimodal MRI Reveals Brainstem Connections that Sustain Wakefulness in Human Consciousness
Edlow BL, Olchanyi M, Freeman HJ, Li J, Maffei C [et al.], Kinney HC
Published in  Science Translational Medicine on 5/1/2024 | Press Release 

Human consciousness requires arousal (i.e., wakefulness) and awareness. Brain imaging studies over the last decade have produced connectivity maps of the cortical networks that sustain awareness, but maps of the subcortical networks that sustain wakefulness are lacking, due to the small size and anatomic complexity of subcortical structures such as the brainstem. In a magnetic resonance imaging (MRI) study that integrated ultra-high resolution structural and functional connectivity data, researchers mapped a subcortical brain network that is believed to integrate arousal and awareness in human consciousness. 

(Summary submitted by Brian Edlow, MD, Department of Neurology) 

Hillocks: A New Airway Barrier Structure
Airway Hillocks Are Injury-resistant Reservoirs of Unique Plastic Stem Cells
Lin B, Shah VS, Chernoff C, Sun J, Shipkovenska GG [et al.], Rajagopal J
Published in  Nature on 5/1/2024 

We have discovered a new airway structure that we call the hillock. Hillocks are composed of tightly interlocking flat cells that act as shields to protect an underlying unique population of highly regenerative basal stem cells. Remarkably, hillocks appear to resist all cardinal forms of environmental damage, ranging from toxins to acid to infection. Hillocks then regenerate the entire airway surface, repopulating all the six types of epithelial cells. We searched for hillocks in human airways and found that not only are they present, but they also recapitulate many of the same properties we uncovered in mice. The discovery of hillocks in mice and human airways has important implications for human diseases ranging from influenza and COVID 19 to lung cancer. Future work will better characterize the role of hillocks in understanding how the airway recovers after these insults and if hillocks are related to squamous cell cancer. 

(Summary submitted by Viral Shah, MD PhD, Center For Regenerative Medicine, Division of Pulmonary and Critical Care, Department of Medicine) 

Improving CAR T Therapy for Pancreatic Cancer
Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma
Wehrli M, Guinn S, Birocchi F, Kuo A, Sun Y [et al.], Maus MV
Published in Clinical Cancer Research on 5/1/2024 

The efficacy of CAR-T cells in solid tumors is hindered by a highly immunosuppressive microenvironment and limited tumor infiltration due to the physical and biological barriers of solid tumors. Cancer-associated fibroblasts (CAFs) contribute to these obstacles by secreting immunosuppressive factors and promoting extracellular matrix deposition. This study utilizes a T-cell-engaging molecule (TEAM) targeting the fibroblast activation protein (FAP) to deplete CAFs (FAP-TEAM). Anti-mesothelin CAR-T cells secreting FAP-TEAM efficiently eliminate PDAC and CAFs in vitro, in vivo and ex vivo patient-derived models and showed superior anti-tumor activity compared to conventional CAR-T cells, demonstrating their potential for treating patients with PDAC. 

(Summary submitted by Marcela V Maus, MD, PhD, Mass General Cancer Center) 

AMERK Serostatus as Predictor of Merkel Cell Carcinoma Outcomes
The Prognostic Value of the Merkel Cell Polyomavirus Serum Antibody Test: A Dual Institutional Observational Study
Miller DM, Shalhout SZ, Wright KM, Miller MA, Kaufman HL [et al.], Thakuria M
Published in  Cancer on 5/2/2024 

Merkel cell carcinoma (MCC) is a serious skin cancer with limited predictive tools. This study explored the AMERK blood test, which detects antibodies linked to MCC, in 261 patients diagnosed within 90 days. Patients with a positive AMERK test, especially those with early-stage cancer, had better recurrence-free, event-free, and overall survival rates. The AMERK test also correlated with tumor burden, indicating higher antibody levels in patients with more extensive disease. The study highlights the potential of the AMERK test in personalizing MCC treatment. However, its retrospective design and exploratory nature are notable limitations. 

(Summary submitted by David M Miller, MD, PhD, Department of Hematology/Oncology) 

Post-Procedure cfDNA Detection Status and Colorectal Cancer Recurrence
Minimal Residual Disease using a Plasma-Only Circulating Tumor DNA Assay to Predict Recurrence of Metastatic Colorectal Cancer Following Curative Intent Treatment
Parikh AR, Chee BH, Tsai J, Rich TA, Price KS [et al.], Atreya CE
Published in Clinical Cancer Research on 5/2/2024 

Circulating tumor DNA has emerged as the most powerful prognostic biomarker in CRC. In this paper, with a blood only ctDNA test, we should that it is also prognostic in Stage IV patients undergoing curative therapies. We think this is a group that is important as cures are possible but recurrence risk is very high. We hope that we will be able to use ctDNA to figure out who the highest risk patients are in order to possible offer new therapies. 

(Summary submitted by Aparna Parikh, MD, Hematology Oncology, Mass General Cancer Center) 

Assessing the Sensitivity and Yield of Inpatient Diagnostic Algorithms for Pulmonary Tuberculosis in a Low-Prevalence Setting
Second Time’s the Charm? Assessing the Sensitivity and Yield of Inpatient Diagnostic Algorithms for Pulmonary Tuberculosis in a Low-prevalence Setting
Dugdale CM, Zachary KC, McEvoy DS, Branda JA, Courtney A [et al.], Shenoy ES
Published in Open Forum Infectious Diseases on 5/3/2024 | Research Spotlight 

When patients with symptoms and history potentially consistent with tuberculosis (TB) present to hospitals, CDC guidelines recommend that they be put in airborne isolation precautions to prevent spread of TB to other people and that they get three sputum specimens with acid-fast bacilli (AFB) smears to “rule out” TB. We found that only 50% of individuals with tuberculosis had positive AFB smears and that two smears were just as good as three smears at diagnosing TB. We also found that newer nucleic acid amplification tests, while not available in all hospitals, were generally better at diagnosing TB than AFB smears. 

(Summary submitted by Caitlin Dugdale, MD, Division of Infectious Diseases, Department of Medicine) 

Clinical Trial Shows that Cytisinicline Can Help People Quit Vaping
Cytisinicline for Vaping Cessation in Adults Using Nicotine E-Cigarettes: The ORCA-V1 Randomized Clinical Trial
Rigotti NA, Benowitz NL, Prochaska JJ, Cain DF, Ball J [et al.], Jacobs C
Published in  JAMA Internal Medicine on 5/6/2024 | Press Release 

Many young adults who are using nicotine e-cigarettes want to quit vaping but have trouble doing so on their own and need help. There are few treatments and no medications approved to help vapers quit. We conducted a randomized placebo-controlled clinical trial of 160 adults who vaped but did not smoke to see whether the medication cytisinicline is an effective and safe pharmacotherapy to help adults stop vaping nicotine e-cigarettes. The study was conducted at MGH and 4 other sites. A 12-week course of cytisinicline along with behavioral support was more effective than placebo with behavioral support and had few side effects. At the end of treatment people receiving the active drug were more than twice as likely to quit vaping (31.8% vs. 15.1%). The study shows that cytisine is a potentially effective and safe pharmacotherapy for vaping cessation in adults who use nicotine e-cigarettes and seek to quit vaping. 

(Summary submitted by Nancy Rigotti, MD, Tobacco Research and Treatment Center, Department of Medicine) 

Proof-of-Mechanism and Clinical Feasibility of Sacituzumab Govitecan
Antibody Drug Conjugate Sacituzumab Govitecan Enables A Sequential TOP1/PARP Inhibitor Cancer Therapy Strategy in Breast Cancer Patients
Bardia A, Sun S, Thimmiah N, Coates JT, Wu B [et al.], Ellisen LW
Published in Clinical Cancer Research on 5/6/2024 

Antibody drug conjugates (ADCs) bind to tumor-specific proteins and deliver potent chemotherapy selectively to tumor cells. We hypothesized that an ADC delivering topoisomerase inhibitor (TOP1i) chemotherapy could be safely combined with another targeted drug known as a PARP inhibitor (PARPi), even though prior clinical trials using systemic TOP1i plus PARPi therapy proved too toxic. This phase 1b clinical trial shows that the tumor-targeted ADC drug delivery mechanism enables staggered dosing of the ADC and PARPi, which overcomes dose-limiting toxicities observed with concurrent dosing. Thus, unique features of ADCs may facilitate novel dosing strategies that render viable previously abandoned therapeutic combinations. 

(Summary submitted by Leif W. Ellisen, MD, PhD, Breast Medical Oncology, MGH Cancer Center) 

Neural States of Cannabis Impairment
Intoxication Due to Δ9-tetrahydrocannabinol is Characterized by Disrupted Prefrontal Cortex Activity
Karunakaran KD, Pascale M, Ozana N, Potter K, Pachas GN, Evins AE, Gilman JM
Published in  Neuropsychopharmacology on 5/7/2024 | Press Release 

This study investigated how THC, the main psychoactive component in cannabis, affects the brain, particularly the prefrontal cortex which is crucial for decision-making and self-control. Researchers conducted a controlled experiment with adults who regularly use cannabis, comparing brain activity under the influence of THC versus a placebo. They found that THC disrupts the normal connections and activity in the prefrontal cortex, leading to potential cognitive impairments. This insight helps explain how cannabis intoxication can affect thinking and behavior, using a portable brain scanning technology 

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

Oncogenic FGFR2 Signaling in Intrahepatic Cholangiocarcinoma
FGFR Inhibition Blocks NF-ĸB-dependent Glucose Metabolism and Confers Metabolic Vulnerabilities in Cholangiocarcinoma
Zhen Y, Liu K, Shi L, Shah S, Xu Q [et al.], Bardeesy N
Published in  Nature Communications on 5/7/2024 

Patients with cholangiocarcinoma (CCA) frequently have abnormal Fibroblast Growth Factor Receptor 2 (FGFR2) function in their tumor cells. FGFR-inhibiting drugs (FGFRi) shrink or slow down the growth of this subset of CCAs. Unfortunately, resistance eventually develops. We recently reported that FGFR2 controls how CCA cells use nutrient sources like glucose and fat. We also identified medicines that when combined with FGFRi in laboratory models of CCA effectively starve the tumor cells of energy and building blocks required for survival and growth. Our work provides insights into the cancer-promoting functions of FGFR2 and suggests potential new treatments for patients FGFR2-altered CCA. 

(Summary submitted by Yuanli Zhen, PhD, Mass General Cancer Center) 

CDK-Rb Pathway Blockade in IDH-Mutant Glioma
CDKN2A/B Homozygous Deletion Sensitizes IDH-mutant Glioma to CDK4/6 Inhibition
Nasser AM, Melamed L, Wetzel E, Chang CC, Nagashima H [et al.], Miller JJ
Published in Clinical Cancer Research on 5/8/2024 

IDH mutant gliomas are a type of adult primary brain tumor that can initially be controlled with radiation and chemotherapy. Unfortunately, these gliomas almost universally recur, causing progressive neurologic decline. The most aggressive of these recurrent tumors lose an important gene known as CDKN2A. Here we showed that the drug abemaciclib, which inhibits the CDK4/6 enzyme, is effective at killing IDH mutant glioma cells that have lost the CDKN2A gene. In animal models, we demonstrated that treatment with abemaciclib slows IDH mutant glioma growth, leading to longer survival times. Abemaciclib is approved for use in other cancer types, highlighting the potential for smoothly translating these data into a clinical trial in patients with IDH mutant glioma. 

(Summary submitted by Julie J. Miller, MD, PhD, Department of Neurology, Mass General Cancer Center) 

Previously Uninvestigated Elastic and Viscous Response in Tissue
Laser Speckle Rheological Microscopy Reveals Wideband Viscoelastic Spectra of Biological Tissues
Leartprapun N, Zeng Z, Hajjarian Z, Bossuyt V, Nadkarni SK
Published in  Science Advances on 5/8/2024 

Biological tissues scale a broad range of mechanical properties, from pliant fatty tissue to hard bone. Abnormal changes in tissue mechanics are recognized as a powerful driver of various diseases including cancer, hematological disorders, and orthopedic conditions. Mechanical signatures of biospecimens can offer unique insights into the disease state and provide prognostic indicators for improved treatment planning. However, current pathology procedures do not comprehensively discern mechanical abnormalities of clinical tissue. In this work, we developed a new tool in the form of a simple upright microscope, called WB-SHEAR, to enable mapping of mechanical signatures of gross unprocessed biospecimens. 

(Summary submitted by Nichaluk Leartprapun, PhD, Wellman Center for Photomedicine, Department of Dermatology) 

A Better Understanding of Immune Checkpoint Inhibitor-Related Colitis
Single-cell Transcriptomic Analyses Reveal Distinct Immune Cell Contributions to Epithelial Barrier Dysfunction in Checkpoint Inhibitor Colitis
Thomas MF, Slowikowski K, Manakongtreecheep K, Sen P, Samanta N [et al.], Villani AC
Published in  Nature Medicine on 5/9/2024 | Research Spotlight 

Immune-related adverse events (irAEs) are side effects experienced by patients undergoing immunotherapy to treat their cancer. These IrAEs can affect up to 90% of patients depending on the dose and combination therapy being used, with up to 55% of patients experiencing severe irAEs that require immunosuppressive therapy or cessation of ICI treatment. Little is known about the mechanistic underpinnings of irAEs, which has resulted in limited targeted treatment options that can mitigate irAEs while preserving the anti-tumor immune responses to ICI therapy. This study focused on defining the biological determinants of immune checkpoint related colitis – inflammation of the colon — which is the most common, severe irAE.  Our study is the first comprehensive study looking at all the non-immune and immune cells from colon tissue and blood from patients with colitis and controls. We have defined the key biological programs leading to colitis and nominated putative promising therapeutic targets to be further investigated. 

(Summary submitted by Alexandra-Chloe Villani, PhD, Krantz Family for Cancer Research and Center for Immunology and Inflammatory Diseases, Department of Medicine) 

Optimizing the Dosing of Lurbinectedin for Leiomyosacroma
Safety And Efficacy Of Combination Lurbinectedin Plus Doxorubicin From A Phase 1b Trial In Patients With Advanced/Metastatic Soft Tissue Sarcoma
Cote GM, Haddox CL, Choy E, Merriam PA, Mazzola E [et al.], George S
Published in  Clinical Cancer Research on 5/9/2024 

The outcomes of patients with metastatic soft tissue sarcoma (STS), including leiomyosarcoma (LMS), remain poor. Standard treatment includes chemotherapy with doxorubicin as a single agent or in combination with other chemotherapy. Multiple efforts attempting to improve on these therapies have been attempted, however, with disappointing results. Lurbinectedin is a novel anti-cancer agent currently approved in the US for the treatment of SCLC. In this phase 1b study in patients with advanced/metastatic STS were treated with lurbinectedin and doxorubicin. We determined that the recommended phase 2 dose of full-dose lurbinectedin with low-dose doxorubicin was safe and tolerable. Enrolled histologies were diverse and there were strong signals of activity in LMS as well as other sarcoma subtypes. Sixty percent of patients saw their tumors shrink by over 30% and the median time on treatment was over 11 months. These encouraging data support the ongoing randomized phase 2 study and a planned phase 3 study in patients with LMS comparing lurbinectedin/doxorubicin with doxorubicin alone. 

(Summary submitted by Gregory M Cote, MD, PhD, Termeer Center for Targeted Therapies, Mass General Cancer Center) 

Differences in Live Expectancy for Youth with HIV
Projected Life Expectancy for Adolescents With HIV in the US
Neilan AM, Ufio OL, Brenner IR, Flanagan CF, Shebl FM [et al.], Patel K
Published in  JAMA Health Forum on 5/10/2024 | Press Release 

This study projected life expectancy for youth with HIV acquired around the time of birth (YPHIV) and in adolescence (YNPHIV), and youth without HIV. Using mathematical simulation modeling and national adolescent clinical data, YPHIV and YNPHIV were projected to have lower life expectancies than youth without HIV. Interventions focused on HIV care as well as social factors associated with disparities in non-HIV-related mortality are needed to improve life expectancy for youth with HIV in the US. 

(Summary submitted by Anne Neilan, MD, MPH, Infectious Disease Unit, Department of Medicine) 

The Genetic Basis by Which Host Immunity Impacts HIV Outcomes
Polymorphic Residues in HLA-B that Mediate HIV Control Distinctly Modulate Peptide Interactions with Both TCR and KIR Molecules
Tano-Menka R, Singh NK, Muzhingi I, Li X, Mandanas MV [et al.], Gaiha GD
Published in Structure on 5/10/2024 

In this study, we systematically assessed the specific residues in human leukocyte antigen (HLA) class I alleles (at positions 67, 70, 97 and 156) that are responsible for the natural control of HIV. Through a detailed evaluation of the protective allele HLA-B*5701, we found that these residues distinctly modulate the stability of HLA-HIV peptide complexes, recognition by T cell receptors and interactions between HLA and killer inhibitory receptors on natural killer cells. While numerous components of host immunity and virologic metrics have been implicated in viral control, this data provides key structural and biochemical evidence for a primary role of T cell and NK cell responses in mediating natural viral suppression, providing additional support for therapeutic epitope-based vaccines currently in clinical development. 

(Summary submitted by Gaurav D Gaiha, MD, Division of Gastroenterology, Department of Medicine) 

Age Affects the Priming of T Cells in the Microenvironment
The Aged Tumor Microenvironment Limits T Cell Control of Cancer
Chen ACY, Jaiswal S, Martinez D, Yerinde C, Ji K [et al.], Sen DR
Published in  Nature Immunology on 5/14/2024 | Research Spotlight 

As people get older, the risk of being diagnosed with cancer increases while the immune system becomes slower to respond. But we don’t fully understand how aging affects the immune system's ability to fight cancer. We studied how aging impacts immune cells called CD8+ killer T cells. We found that as we age, the tumor microenvironment weakens these T cells, making them less effective at fighting cancer. However, we can reinvigorate other helper immune cells such as myeloid to overcome this defect in aged tumors, offering potential new ways to improve cancer therapy in older individuals. 

(Summary submitted by Debattama (Deb) Sen, PhD, Krantz Center for Cancer Research, Mass General Cancer Center ) 

Polygenic Screenings Have High Public Approval and Interest
Public Attitudes, Interests, and Concerns Regarding Polygenic Embryo Screening
Furrer RA, Barlevy D, Pereira S, Carmi S, Lencz T, Lázaro-Muñoz G
Published in  JAMA Network Open on 5/14/2024 

Polygenic Embryo Screening (PES) is used in the context of IVF to screen the DNA of embryos and estimate their likelihood of developing complex health conditions and traits. A survey of US adults published in JAMA Network Open revealed high approval and interest in PES, despite pronounced concerns about false expectations and societal implications. When potential concerns were presented at the beginning of the survey, approval decreased, and uncertainty increased. These findings underscore the urgent need for informed dialogue and comprehensive guidance around the ethical development of this technology. 

(Summary submitted by Rémy Furrer, PhD, Center for Bioethics, Harvard Medical School) 

Supporting Research of Populations with Diverse Ancestry
A Harmonized Public Resource of Deeply Sequenced Diverse Human Genomes
Koenig Z, Yohannes MT, Nkambule LL, Zhao X, Goodrich JK [et al.], Martin AR
Published in Genome Research on 5/15/2024 

We harmonized 4,094 whole genomes from 80 populations in the Human Genome Diversity and 1000 Genomes Projects (HGDP and 1kGP) with data from the Genome Aggregation Database (gnomAD). With these data, we identified over 153 million high-quality variants and cataloged millions of new and mostly rare genetic variants, demonstrating substantial added value compared to prior versions. Further, we characterized population structure at global and subcontinental levels, and explored patterns of ancestry composition across populations. We provide unrestricted access to individual-level data, detailed tutorials for conducting analyses in a cloud-computing environment, and a resource of haplotypes for phasing and imputation. 

(Summary submitted by Mary T. Yohannes, Broad Institute) 

PRC2 Preferentially Binds Folded rG4s
G-quadruplex Folding in Xist RNA Antagonizes PRC2 Activity for Stepwise Regulation of X Chromosome Inactivation
Lee YW, Weissbein U, Blum R, Lee JT
Published in Molecular Cell on 5/16/2024 

Just like proteins, RNAs fold into functional structures. RNA G-quadruplexes (rG4s) arise from guanine-rich sequences, that allow the formation of stacked planar tetrads called G-quartets. There has been great interest in understanding how rG4s impact RNA-mediated gene regulation because of frequent guanine-rich regions in mammalian RNAs. However, our understanding of rG4s has been limited by a lack of information about where they fold. Here, we identified rG4s in cells, including a few in Xist, the long noncoding RNA essential for X chromosome inactivation. We demonstrate rG4 structures on Xist and find that they regulate the deposition of repressive epigenetic mark, which confers X chromosome inactivation in a coordinated manner. rG4 structures therefore play a crucial role in epigenetic regulation. 

(Summary submitted by YongWoo Lee, PhD, Department of Molecular Biology) 

Predicting Chemotherapy Response in Pancreatic Cancer
Allysine-Targeted Molecular MRI Enables Early Prediction of Chemotherapy Response in Pancreatic Cancer
Ma H, Esfahani SA, Krishna S, Ataeinia B, Zhou IY [et al.], Caravan P
Published in Cancer Research on 5/17/2024 

Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related deaths and has a dismal prognosis. A major challenge in PDAC patient management is that standard imaging methods do not accurately show the change in size or resectability of the residual tumor tissue. We invented a molecular MRI probe that targets a marker formed as dead cancer cells are replaced by scar tissue. Here, in mouse models we showed that molecular MRI performed after one dose of chemotherapy could accurately predict whether the mouse would have a positive or negative response to a full course of chemotherapy. 

(Summary submitted by Hua Ma, PhD and Peter Caravan, PhD, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radioloogy) 

Higher Consumption of Ultra-Processed Foods Leads to Worse Brain Health
Associations Between Ultra-Processed Food Consumption and Adverse Brain Health Outcomes
Bhave VM, Oladele CR, Ament Z, Kijpaisalratana N, Jones AC [et al.], Kimberly WT
Published in  Neurology on 5/22/2024 | Press Release 

Ultra-processed foods are dietary items that contain additives, preservatives, and are often packaged as ready-to-eat meals, snacks, or sweets. High consumption of these foods in the long term can lead to greater risk of stroke and cognitive impairment, two of the major contributors to brain health. 

Brain Imaging Study Reveals Connections Critical to Human Consciousness
Featuring Brian Edlow, MD 

Human consciousness requires arousal (i.e., wakefulness) and awareness. Brain imaging studies over the last decade have produced connectivity maps of the cortical networks that sustain awareness, but maps of the subcortical networks that sustain wakefulness are lacking, due to the small size and anatomic complexity of subcortical structures such as the brainstem. In a magnetic resonance imaging (MRI) study that integrated ultra-high resolution structural and functional connectivity data, researchers mapped a subcortical brain network that is believed to integrate arousal and awareness in human consciousness. 

Clinical Trial Shows that Cytisinicline Can Help People Quit Vaping
Featuring Nancy A. Rigotti, MD 

In a randomized clinical trial including adults who vaped nicotine e-cigarettes but did not smoke cigarettes, a 12-week course of cytisinicline, a plant-based medication, was more effective at helping people quit e-cigarettes than placebo when both were combined with behavioral support. Results from the trial, which was co-led by a researcher from Massachusetts General Hospital, suggest that cytisinicline may be a promising treatment for vaping cessation. 

Clinicians Report Success with First Test of Drug in a Patient with Life-Threatening Blood Clotting Disorder
Featuring Pavan K. Bendapudi, MD 

Immune thrombotic thrombocytopenic purpura, a rare blood clotting disorder, results from an autoimmune attack against an enzyme called ADAMTS13. A recombinant form of human ADAMTS13 approved for a different condition helped to save the life of a young mother with immune thrombotic thrombocytopenic purpura. Results from this first use of the drug for this condition—by a team led by researchers from Massachusetts General Hospital—warrants testing the drug in a clinical trial. 

Yoga and Meditation-Induced Altered States of Consciousness are Common in the General Population
Featuring Matthew D. Sacchet, PhD 

Yoga, mindfulness, meditation, breathwork, and other practices can foster altered states of consciousness. In a study of adults in the general population, a team including researchers from Massachusetts General Hospital found that a surprisingly high percentage of participants (45%) reported experiencing altered states of consciousness. Strikingly, almost one-fifth of the respondents reported experiences of suffering following altered states of consciousness. 

Increasing Life Expectancy for Youth with HIV Requires More Than Just Adherence to Care Regimens
Featuring Anne Neilan, MD, MPH 

Mass General study projects life expectancy gaps of 10.4 years and 11.8 years for male and female youths, respectively, living with HIV compared to individuals without HIV. Life expectancy improves for youth who acquired HIV at birth when current care and treatment guidelines are actively followed. Additional social and structural interventions are likely required to improve life expectancy for youth who acquired HIV in adolescence, as adherence to care did not have the same effects on life expectancy 

Study Finds an Association Between a Higher Consumption of Ultra-Processed Foods and Greater Risk of Stroke and Cognitive Decline
Featuring W. Taylor Kimberly, MD, PhD 

Researchers examined the association between the consumption of ultra-processed foods—items that contain additives and preservatives such as snacks and sweets—and rates of stroke and cognitive impairment. They found that the increased consumption of these foods was associated with a higher risk of both stroke and cognitive decline, and the risk was even more elevated in Black patients. Even modest cutbacks in the consumption of ultra processed foods were associated with positive health benefits. 

Century-old Vaccine Protects Type 1 Diabetics from Infectious Diseases
Featuring Denise Faustman, MD, PhD 

Researchers from Massachusetts General Hospital conducted a Phase III trial to test the 100-year-old Bacillus Calmette-Guérin (BCG) vaccine in people with type 1 diabetes during the COVID-19 pandemic. The objective of this research was to determine if the BCG vaccine protected type 1 diabetics from all infectious diseases, including COVID-19. In the MGH trial, BCG-treated individuals had a significantly lower rate of COVID-19 infection compared with the placebo group and a significantly lower rate of infectious diseases overall. 

Statin Therapy May Prevent Cancer by Blocking Inflammatory Protein
Featuring Shawn Demehri, MD, PhD 

A team led by investigators from Mass General Cancer Center found that statins—commonly used cholesterol-lowering drugs—may block a pathway that leads to the development of cancer in the context of chronic inflammation. The team’s experiments showed that environmental toxins, such as those caused by exposure to allergens and chemical irritants, create a cascade effect that stimulates inflammation in the skin and pancreas that can lead to cancer. Their findings suggest that using statins to suppress this pathway may have a protective effect against the development of cancer that results from chronic inflammation. 

Brain Imaging Study Shows How THC in Cannabis Disrupts Brain Activity and May Cause Cognitive Impairment
Featuring Jodi M. Gilman, PhD 

In a double-blind, randomized, cross-over study of adults who use cannabis regularly, researchers from Massachusetts General Hospital assessed participants’ brain activity under the influence of THC (the main psychoactive component in cannabis) versus placebo. Compared with placebo, THC led to reduced connections and activity within the brain’s prefrontal cortex, a region important for decision-making and self-control. THC was also associated with connectivity changes that could impair the brain from efficiently adapting or reconfiguring to changing stimuli 

What are Special Purpose Acquisition Companies in the U.S. Healthcare System?
Featuring Zirui Song, MD, PhD 

Zirui Song, MD, PhD, a physician investigator in the Department of Medicine at Massachusetts General Hospital and an associate professor of Health Care Policy and Medicine at Harvard Medical School, is the senior author of a recently published perspective in the New England Journal of Medicine, "Corporate Medicine 2.0 — Special Purpose Acquisition Companies in the United States". The article’s lead author is Nishant Uppal, MD, MBA, a resident at Brigham and Women’s Hospital. 

How inflammation damages synapses in an experimental model of multiple sclerosis
Featuring Rebecca Gillani, MD, PhD 

Rebecca Gillani, MD, PhD, a physician investigator in the Department of Neurology at Massachusetts General Hospital and an Instructor in Neurology at Harvard Medical School, is the lead author of a recently published paper in Brain, Behavior, and Immunity; "Instability of Excitatory Synapses in Experimental Autoimmune Encephalomyelitis and the Outcome for Excitatory Circuit Inputs To Individual Cortical Neurons". 

Orthopaedic Surgery Volume Trends During the COVID-19 Pandemic and Post-Vaccination Era
Featuring Marc Succi, MD 

Marc Succi, MD, a physician investigator in the Department of Radiology at Massachusetts General Hospital, associate chair of innovation and commercialization at Mass General Brigham Enterprise Radiology and an assistant professor of Radiology at Harvard Medical School, is the lead author of a recently published paper in Journal of Arthroplasty, "Orthopaedic Surgery Volume Trends During the COVID-19 Pandemic and Post-Vaccination Era: Implications for Healthcare Planning" 

A Better Understanding of Immune Checkpoint Inhibitor-Related Colitis
Featuring Alexandra-Chloe Villani, PhD, Kerry Reynolds, MD, Dr. Molly Fisher Thomas, and Dr. Kamil Slowikowski 

Alexandra-Chloe Villani, PhD, an investigator in the Krantz Family for Cancer Research and the Center for Immunology and Inflammatory Diseases at Massachusetts General Hospital and an assistant professor of Medicine at Harvard Medical School and Institute Member of the Broad Institute, is a corresponding author of a new study in Nature Medicine entitled "Single-Cell Transcriptomic Analyses Reveal Distinct Immune Cell Contributions to Epithelial Barrier Dysfunction in Checkpoint Inhibitor Colitis". Dr. Villani co-supervised together with Kerry Reynolds, MD, Clinical Director of the Inpatient Oncology Units and Director of the Severe Immunotherapy Complication Program. She is also an assistant professor of Medicine at Harvard Medical School. This work was co-led by two postdoctoral fellows—Dr. Molly Fisher Thomas, a gastroenterologist physician scientist and immunologist who is now on faculty as an assistant professor at the Oregon Health & Science University, and Dr. Kamil Slowikowski who is a computational postdoctoral fellow in the Villani Lab. 

Assessing the Sensitivity and Yield of Inpatient Diagnostic Algorithms for Pulmonary Tuberculosis in a Low-Prevalence Setting
Featuring Caitlin Dugdale, MD 

Caitlin Dugdale, MD, a physician-investigator in the Division of Infectious Diseases at Massachusetts General Hospital and an Assistant Professor of Medicine at Harvard Medical School, is the lead author of a new study in Open Forum Infectious Diseases, "Second Time’s the Charm? Assessing the Sensitivity and Yield of Inpatient Diagnostic Algorithms for Pulmonary Tuberculosis in a Low-Prevalence Setting". 

Migration of Microorganisms in the Gut as the Result of Long Term Use of Proton Pump Inhibitors
Featuring Hanseul Kim, PhD 

Hanseul Kim, PhD, a postdoctoral research fellow in the Division of Gastroenterology at Massachusetts General Hospital, is the lead author of a recently published research letter in the journal Gastroenterology, "Altered Microbial Transcription in Long-Term Proton Pump Inhibitor Usage: Findings From a US Cohort Study". 

Maternal Insulin Sensitivity/Resistance During Pregnancy
Featuring Camille E. Powe, MD 

Camille E. Powe, MD, a physician investigator in the Division of Endocrinology, Department of Medicine and Department of Obstetrics and Gynecology at Massachusetts General Hospital and an associate professor at Harvard Medical School, and a team of investigators in both Medicine and Obstetrics and Gynecology at MGH published the results of a new study in Nature Medicine, "Placental IGFBP1 Levels During Early Pregnancy and the Risk of Insulin Resistance and Gestational Diabetes". 

Aging Weakens T Cells in the Tumor Microenvironment Making Them Less Effective at Fighting Cancer
Featuring Debattama (Deb) Sen, PhD 

Debattama (Deb) Sen, PhD, an assistant investigator in the Krantz Center for Cancer Research in the Mass General Cancer Center and an assistant professor of Medicine at Harvard Medical School, is the corresponding author of a new study in Nature Immunology, "The Aged Tumor Microenvironment Limits T Cell Control of Cancer". 

Differences in the Breakdown of PET Tracer in Awake and Anesthetized States
Featuring Pedro Brugarolas, PhD and Karla Ramos-Torres, PhD 

Pedro Brugarolas, PhD, an investigator at the Center of Nuclear Medicine and Theranostic Sciences at Massachusetts General Hospital and an assistant professor of Radiology at Harvard Medical School, is the corresponding author of a new study in the Journal of Neurochemistry, "Common Anesthetic Used in Preclinical Imaging Inhibits Metabolism of the PET Tracer". Karla Ramos-Torres, PhD, an instructor in investigation in the Department of Radiology at Mass General and an instructor of Radiology at Harvard Medical School, is first author. 

Long-Coding RNAs Act as Scaffolds for Assembling Heterochromatin
Featuring Mo Motamedi, PhD 

Mo Motamedi, PhD, an assistant investigator in the Mass General Cancer Center and an assistant professor of Medicine at Harvard Medical School, is the James & Patricia Poitras Endowed Chair in Cancer Research and the senior author of a new paper in Cell, "RNA Quality Control Factors Nucleate Clr4/SUV39H and Trigger Constitutive Heterochromatin Assembly". 

Remembering Margaret Reilly, a Longtime Mass General Nurse and Pioneer in Dermatology
A Massachusetts General Hospital nurse for 50 years, Margaret “exemplified the best ideals of health teacher, advice-giver, and care-taker.” 

Snapshot of Science: Mass General’s High Impact Research Publications for April 2024
Increase the sensitivity of liquid biopsies, neurons in the human brain able to predict what we’re going to say before we say it and much more 

Through the Magnifying Glass: The Edlow Lab
How Andrea Edlow, MD, MSc and her team are studying immunization during pregnancy, and its role in maternal and fetal health. 

How Malnourished Organoids Could Play a Key Role in the Quest for a Vaccine Against Shigella
Mass General researcher Christina Faherty, PhD, is using creative techniques to better understand the mechanisms of shigella infection. 

The Next Wave of Meditation Research Will Look to Advanced Practitioners for Insights
You might have heard of the term ‘mindfulness’, a commonly known practice that involves maintaining attention or awareness of the present moment without making judgments. 

Pilot Study Shows Promise of Virtual Reality in Improving Treatment Outcomes for Opioid Withdrawal
Patients who participated in a virtual reality intervention during treatment for opioid withdrawal were more likely to complete their treatment protocol.