Welcome to our Snapshot of Science for July 2020

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 18 summaries submitted by the research teams
  • 10 new research-related press releases from the Mass General Public Affairs office
  • 7 posts from the Mass General Research Institute blog
Publications

POTENTIAL COLITIS TREATMENT TARGETS
Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy
Luoma AM, Suo S, Williams HL, Sharova T, Sullivan K [et al.], Wucherpfennig KW.
Published in Cell on June 25, 2020 | *Summary available


LIPID REQUIREMENTS OF THE MITOCHONDRIAL CALCIUM UNIPORTER
An Essential Role for Cardiolipin in the Stability and Function of the Mitochondrial Calcium Uniporter
Ghosh S, Ball WB, Madaris TR, Srikantan S, Madesh M [et al.], Gohil VM.
Published in PNAS on June 29, 2020


PENICILLIN ALLERGY ASSESSMENTS TO REDUCE ALTERNATIVE ANTIBIOTIC USE
Association Between Penicillin Allergy Documentation and Antibiotic Use
Blumenthal KG, Kuper K, Schulz LT, Bhowmick T, Postelnick M [et al.], Walensky RP.
Published in JAMA Internal Medicine on June 29, 2020 | *Summary available | Press Release


CONTROLLING GENE DRIVES WITH SMALL MOLECULES
Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives
López Del Amo V, Leger BS, Cox KJ, Gill S, Bishop AL [et al.], Choudhary A.
Published in Cell Reports on June 30, 2020 | *Summary available


INSIGHTS INTO OSTEOCYTE RESPONSE TO EXERCISE
A FAK/HDAC5 Signaling Axis Controls Osteocyte Mechanotransduction
Sato T, Verma S, Castro Andrade CD, Omeara M, Campbell N [et al.], Wein MN.
Published in Nature Communications on July 1, 2020 | *Summary available


EVALUATING POST-TREATMENT FIBROSIS IN PDAC PATIENTS
Fibrotic Response to Neoadjuvant Therapy Predicts Survival in Pancreatic Cancer and Is Measurable with Collagen-targeted Molecular MRI
Erstad DJ, Sojoodi M, Taylor MS, Clavijo Jordan V, Farrar CT [et al.], Fuchs BC.
Published in Clinical Cancer Research on July 1, 2020


MITRAL VALVE REPAIR RATES AND OUTCOMES
Volume-Outcome Association of Mitral Valve Surgery in the United States
Badhwar V, Vemulapalli S, Mack MA, Gillinov AM, Chikwe J [et al.], Shahian DM.
Published in JAMA Cardiology on July 1, 2020 | *Summary available


IMPROVING CHLAMYDIA SCREENING FOR YOUNG ADULTS
Increasing Vaginal Chlamydia Trachomatis Testing in Adolescent and Young Adults
Brigham KS, Peer MJ, Ghoshhajra BB, Co JPT.
Published in Pediatrics on July 1, 2020 | *Summary available


LIN28B TARGET FOR PANCREATIC CANCER TREATMENT
Pancreatic Circulating Tumor Cell Profiling Identifies LIN28B as a Metastasis Driver and Drug Target
Franses JW, Philip J, Missios P, Bhan I, Liu [et al.], Ting DT.
Published in Nature Communications on July 3, 2020 | *Summary available


PANAMA-SCORE PREDICTS PANCREATIC CANCER CHEMOTHERAPY PROGNOSIS
A Combination of Biochemical and Pathological Parameters Improves Prediction of Postresection Survival After Preoperative Chemotherapy in Pancreatic Cancer: The PANAMA-score
Gruenewald J, Zhou R, Lareau CA, Garcia SP, Iyer S [et al.], Joung JK.
Published in Annals of Surgery on July 7, 2020


MICROFLUIDIC CIRCULATING TUMOR CELL SORTING FROM LEUKAPHERESIS PRODUCTS
Ultrahigh-throughput Magnetic Sorting of Large Blood Volumes for Epitope-Agnostic Isolation of Circulating Tumor Cells
Mishra A, Dubash TD, Edd JF, Jewett MK, Garre SG [et al.], Toner M.
Published in PNAS on July 8, 2020 | *Summary available


LENGTH OF POLYQ IMPACTS HUNTINGTIN PROTEIN
The Polyglutamine Expansion at the N-Terminal of Huntingtin Protein Modulates the Dynamic Configuration and Phosphorylation of the C-Terminal HEAT Domain
Jung T, Shin B, Tamo G, Kim H, Vijayvargia R [et al.], Song J.
Published in Structure on July 8, 2020 | *Summary available


CELL TYPES INVOLVED IN TENDON CELL REGENERATION
Tendon Cell Regeneration Is Mediated by Attachment Site-Resident Progenitors and BMP Signaling
Niu X, Subramanian A, Hwang TH, Schilling TF, Galloway JL.
Published in Current Biology on July 9, 2020 | *Summary available


MULTI-OMICS CLUSTERING REVEALS FOUR SUBGROUPS OF LUNG ADENOCARCINOMA
Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma
Gillette MA, Satpathy S, Cao S, Dhanasekaran SM, Vasaikar SV, [et al.] Carr SA.
Published in Cell on July 9, 2020 | *Summary available


U.S. POSTOPERATIVE OPIOID PRESCRIBING RATES 
Opioids After Surgery in the United States Versus the Rest of the World: The International Patterns of Opioid Prescribing (iPOP) Multicenter Study
Kaafarani HMA, Han K, El Moheb M, Kongkaewpaisan N, Jia Z [et al.], Lillemoe KD.
Published in Annals of Surgery on July 9, 2020 | *Summary available


PERCEIVED VALUE OF PATIENT-REPORTED OUTCOME MEASURES
The Surgeon's Perceived Value of Patient-reported Outcome Measures (PROMs): An Exploratory Qualitative Study of 5 Different Surgical Subspecialties
Mou D, Sisodia RC, Castillo-Angeles M, Ladin K, Bergmark RW [et al.], Heng M.
Published in Annals of Surgery on July 9, 2020


NEAR-INFRARED GUIDED SENTINEL LYMPH NODE IDENTIFICATION FACTORS
Finding the "True" N0 Cohort: Technical Aspects of Near-infrared Sentinel Lymph Node Mapping in Non-small Cell Lung Cancer
Phillips WW, Weiss KD, Digesu CS, Gill RR, Mazzola E [et al.], Colson YL.
Published in Annals of Surgery on July 9, 2020


A POTENTIAL THERAPEUTIC APPROACH TO HLRCC
Nitrogen Trapping as a Therapeutic Strategy in Tumors with Mitochondrial Dysfunction
Madala HR, Helenius IT, Zhou W, Mills E, Zhang Y [et al.], Yeh JJ.
Published in Cancer Research on July 10, 2020 | *Summary available


MICROTUBULE COHERENCE AND IN VIVO TUMOR CELL DYNAMICS
In Vivo Microscopy Reveals Macrophage Polarization Locally Promotes Coherent Microtubule Dynamics in Migrating Cancer Cells
Luthria G, Li R, Wang S, Prytyskach M, Kohler RH [et al.], Miller MA.
Published in Nature Communications on July 14, 2020 | *Summary available


PHASE I TRIAL OF BRAF INHIBITOR AND MEK INHIBITOR
A Phase 1b/2 Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAF V600E/K-mutant Solid Tumors
Sullivan RJ, Weber JS, Patel SP, Dummer R, Carlino MS [et al.] Ascierto PA.
Published in Clinical Cancer Research on July 15, 2020 | *Summary available


GENDER AND DIFFERENCES IN FACULTY PERFORMANCE ASSESSMENTS
Association of Gender with Learner Assessment in Graduate Medical Education
Klein R, Ufere NN, Rao SR, Koch J, Volerman A [et al.], Palamara K.
Published in JAMA Open Network on July 16, 2020


DIFFERENTIATING NON-CELIAC GLUTEN SENSITIVITY FROM CELIAC DISEASE
Subclass Profile of IgG Antibody Response to Gluten Differentiates Non-Celiac Gluten Sensitivity from Celiac Disease
Uhde M, Caio G, De Giorgio R, Green PH, Volta U, Alaedini A.
Published in Gastroenterology on July 20, 2020 | *Summary available


PAZOPANIB ND NEOADJUVANT CHEMOTHERAPY FOR SOFT TISSUE ADENOCARINOMA
Pathological Response in Children and Adults with Large Unresected Intermediate-grade or High-grade Soft Tissue Sarcoma Receiving Preoperative Chemoradiotherapy with or Without Pazopanib (ARST1321): A Multicentre, Randomised, Open-label, Phase 2 Trial
Weiss AR, Chen Y, Scharschmidt TJ, Chi Y, Tian J [et al.] Wang D.
Published in Lancet Oncology on July 20, 2020


COMBINATION THERAPY FOR METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA
Phase 1b Study of Wnt Inhibitor Ipafricept (IPA) with Gemcitabine and Nab-paclitaxel in Patients with Previously Untreated Stage IV Pancreatic Cancer (mPDAC)
Dotan E, Cardin DB, Lenz H, Messersmith WA, O'Neil BH [et al.], Weekes CD.
Published in Clinical Cancer Research on July 21, 2020


GENETIC RISK FOR OBESITY TIED TO WORKPLACE FOOD PURCHASES
Polygenic Risk Score for Obesity and the Quality, Quantity, and Timing of Workplace Food Purchases: A Secondary Analysis from the ChooseWell 365 Randomized Trial
Dashti HS, Hivert M, Levy D, McCurley JL, Saxena R, Thorndike AN.
Published in PLOS Medicine on July 21, 2020 | *Summary available


IMPROVING MALARIA VACCINES
Mapping Functional Humoral Correlates of Protection Against Malaria Challenge Following RTS,S/AS01 Vaccination
Suscovich TJ, Fallon JK, Das J, Demas AR, Crain J [et al.] Alter G.
Published in Science Translational Medicine on July 22, 2020 | *Summary available

Summaries

POTENTIAL COLITIS TREATMENT TARGETS
Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy
Luoma AM, Suo S, Williams HL, Sharova T, Sullivan K [et al.], Wucherpfennig KW.
Published in Cell on June 25, 2020

Checkpoint blockade immunotherapy has revolutionized the treatment of cancer, activating the immune system to attack tumors by disabling key immune regulatory receptors. However, checkpoint blockade also leads to a wide variety of inflammatory toxicities that come from inappropriate activation of the immune system against normal organs. These toxicities are particularly interesting because they reveal information about how the immune system is regulated. In this research we performed the first detailed immune analysis of colitis induced by blockade of the immune checkpoint receptor CTLA-4. We found that this form of colitis is driven by massive expansion of cytotoxic CD8 T cells, many of which are related to resident memory T cells found in the gut mucosa, and we identified multiple potential new colitis treatment targets.

(Summary submitted by Michael Dougan, MD, PhD, Division of Gastroenterology, Department of Medicine and Digestive Healthcare Center )


PENICILLIN ALLERGY ASSESSMENTS TO REDUCE ALTERNATIVE ANTIBIOTIC USE
Association Between Penicillin Allergy Documentation and Antibiotic Use
Blumenthal KG, Kuper K, Schulz LT, Bhowmick T, Postelnick M [et al.], Walensky RP.
Published in JAMA Internal Medicine on June 29, 2020

Approximately half of hospitalized patients receive antibiotics, and more than 10% of these patients have a documented penicillin allergy. Hospitalized patients with ongoing infections who report an allergy to penicillin have an increased risk of adverse drug events, including Clostridioides difficile infection, when not treated with a β-lactam antibiotic. In a cross-sectional study of almost 11,000 inpatients being treated with antibiotics from more than 100 US hospitals, we found that a documented penicillin allergy conferred a two-fold increased odds of β-lactam alternative antibiotic use, with clindamycin use over five-fold. Patients with documented penicillin allergies on antibiotics for surgical prophylaxis had an over seven-fold increased use of β-lactam alternative antibiotics. Given that most patients with a documented penicillin allergy are not truly penicillin-allergic, inpatient penicillin allergy assessments might reduce β-lactam alternative antibiotic use.

(Summary submitted by Kimberly Blumenthal, MD, MSc, Division of Rheumatology, Allergy, and Immunology, Department of Medicine and Mongan Institute)


CONTROLLING GENE DRIVES WITH SMALL MOLECULES
Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives
López Del Amo V, Leger BS, Cox KJ, Gill S, Bishop AL [et al.], Choudhary A.
Published in Cell Reports on June 30, 2020

A gene drive is a genetic engineering technology designed to spread a specific gene through a population at higher-than-normal rates of inheritance (100% of offspring rather than the natural 50% probability). The method capitalizes on the gene-editing tool CRISPR/Cas9 to alter or silence a specific gene or insert a new one. Altering the genomes of entire animal populations could help to defeat disease (e.g., malaria) and control pests, but researchers worry about the consequences of unleashing this new technology. Consequently, we have developed a modified Cas9 protein that responds to a synthetic, orally available small molecule, fine-tuning the inheritance probability. This system opens a new avenue to feasibility studies for spatial and temporal control of gene drives using small molecules.

(Summary submitted by James Walker, PhD, Center for Genomic Medicine and Department of Neurology)


INSIGHTS INTO OSTEOCYTE RESPONSE TO EXERCISE
A FAK/HDAC5 Signaling Axis Controls Osteocyte Mechanotransduction
Sato T, Verma S, Castro Andrade CD, Omeara M, Campbell N [et al.], Wein MN.
Published in Nature Communications on July 1, 2020

Our skeleton is a highly dynamic organ that constantly adapts to external forces. During spaceflight, astronauts lose tremendous amounts of bone mass; conversely, physical exercise stimulates new bone formation. The pathways used by bone cells to sense external mechanical cues are poorly understood. In this publication, we discovered a novel signaling pathway used by osteocytes, cells buried deep within mineralized bone tissue, to respond to exercise. This work has important implications for the development of new treatments to boost skeletal responses to exercise in aging individuals.

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


MITRAL VALVE REPAIR RATES AND OUTCOMES
Volume-Outcome Association of Mitral Valve Surgery in the United States
Badhwar V, Vemulapalli S, Mack MA, Gillinov AM, Chikwe J [et al.], Shahian DM.
Published in JAMA Cardiology on July 1, 2020

Early intervention is increasingly recommended for patients with severe primary degenerative mitral regurgitation, but successful repair rates and survival vary across providers. In our study, we found repair rates for primary mitral regurgitation were higher in the highest vs. lowest volume quartiles. The lowest vs highest hospital volume quartile had significantly higher one-year risk-adjusted mortality, with similar findings at the surgeon level. These data confirm a significant volume-outcome association for mitral valve repair and potentially better results by more experienced providers.

(Summary submitted by David M. Shahian, MD, Codman Center, Department of Surgery, Center for Quality and Safety)


IMPROVING CHLAMYDIA SCREENING FOR YOUNG ADULTS
Increasing Vaginal Chlamydia Trachomatis Testing in Adolescent and Young Adults
Brigham KS, Peer MJ, Ghoshhajra BB, Co JPT.
Published in Pediatrics on July 1, 2020

Chlamydia is the most common reported sexually transmitted infection in the United States, and if untreated, it can have long lasting negative effects on the health of women. Using quality improvement interventions, pediatricians switched from screening for chlamydia in female adolescent and young adults by using a less effective urine test to the more effective vaginal swab test. Standardizing processes, such as stocking exam rooms with the correct swab and determining how the swabs would get to the lab, were more effective than solely educating the providers that the vaginal swab was a more effective test.

(Summary submitted by Katie Brigham, MD, Mass General Hospital for Children)


LIN28B TARGET FOR PANCREATIC CANCER TREATMENT
Pancreatic Circulating Tumor Cell Profiling Identifies LIN28B as a Metastasis Driver and Drug Target
Franses JW, Philip J, Missios P, Bhan I, Liu [et al.], Ting DT.
Published in Nature Communications on July 3, 2020

Pancreatic cancer lethality is due to the distant spread of the disease via the bloodstream. We utilized a microfluidic device developed at Mass General to purify rare circulating tumor cells (CTCs) from the blood of patients with all stages of pancreatic cancer. We identified elevated expression of the LIN28B gene in CTCs from a subset of these patients, which correlated with worse outcomes. When we knocked this gene out or used chemical inhibitors to block its function, we found that pancreatic cancer cells were less aggressive in our experimental models. Therefore, targeting of this protein guided by CTC LIN28B expression may represent a new way to treat pancreatic cancer by halting their ability to spread to distant organs.

(Summary submitted by Joseph Franses, MD, PhD, Division of Hematology/Oncology, Mass General Cancer Center and Department of Medicine)


MICROFLUIDIC CIRCULATING TUMOR CELL SORTING FROM LEUKAPHERESIS PRODUCTS
Ultrahigh-throughput Magnetic Sorting of Large Blood Volumes for Epitope-Agnostic Isolation of Circulating Tumor Cells
Mishra A, Dubash TD, Edd JF, Jewett MK, Garre SG [et al.], Toner M.
Published in PNAS on July 8, 2020

Circulating tumor cell (CTC)-based liquid biopsies provide unique opportunities for cancer diagnostics, cancer treatment selection, and real-time response monitoring. However, given a small number of CTCs present in standard 10 mL blood samples, very large blood volumes must be screened to provide enough CTCs for reliable clinical applications. Now, by combining routinely used clinical leukapheresis with advanced microfluidic cell sorting, we have described a new ultrahigh-throughput microfluidic chip (the LPCTC-iCHIP) that can screen CTCs from an entire human body. The LPCTC-iCHIP uses negative depletion of red blood cells, platelets, and leukocytes which allows isolation of potentially viable CTCs without bias for expression of specific tumor epitopes, making this platform applicable to all solid tumors.

(Summary submitted by Avanish Mishra, PhD, Department of Surgery, and Mehmet Toner, PhD, Department of Surgery, Center for Engineering in Medicine and BioMEMS Center)


LENGTH OF POLYQ IMPACTS HUNTINGTIN PROTEIN
The Polyglutamine Expansion at the N-Terminal of Huntingtin Protein Modulates the Dynamic Configuration and Phosphorylation of the C-Terminal HEAT Domain
Jung T, Shin B, Tamo G, Kim H, Vijayvargia R [et al.], Song J.
Published in Structure on July 8, 2020

Huntington’s Disease (HD) is a brain disorder caused by a genetic mutation that causes victims to have a different version of huntingtin, an important protein produced in the body. How this protein causes the disease to unfold is unknown. A high resolution image of the protein procured by state-of-the-art microscopy has shed new light on the potential cause of HD, but the exact mechanism remains unknown. We have acquired novel high resolution images that have revealed a previously unknown region of the huntingtin protein that may provide a major clue to how this mutation can cause cognitive decline.

(Summary submitted by Ihn Sik Seong, PhD, Center for Genomic Medicine and Department of Neurology)


CELL TYPES INVOLVED IN TENDON CELL REGENERATION
Tendon Cell Regeneration Is Mediated by Attachment Site-Resident Progenitors and BMP Signaling
Niu X, Subramanian A, Hwang TH, Schilling TF, Galloway JL.
Published in Current Biology on July 9, 2020

Tendons connect muscle to bone and enable movement. Injuries to these connective tissues are common but have poor healing potential. Current treatments for tendon injuries are limited, largely owing to our incomplete knowledge of tendon biology. Using a genetic means to remove all tendon cells and thereby damage tendon tissues, we found that the zebrafish has robust abilities to fully regenerate their tendons. This is accomplished through the recruitment of progenitor cells from adjacent connective tissues and requires the BMP signaling pathway. This work helps us to better understand the cell types and cues regulating tendon regeneration that could impact the design of new therapies to promote tendon repair.

(Summary submitted by Jenna Galloway, PhD, Center for Regenerative Medicine and Department of Orthopaedic Surgery)


MULTI-OMICS CLUSTERING REVEALS FOUR SUBGROUPS OF LUNG ADENOCARCINOMA
Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma
Gillette MA, Satpathy S, Cao S, Dhanasekaran SM, Vasaikar SV, [et al.], Carr SA.
Published in Cell on July 9, 2020

Despite advances in lung cancer genetics and immunology, overall five-year lung cancer survival remains less than 20% and new approaches are needed. While the cancer genome provides the blueprints for cancer development, tumor proteins and their modifications are the building blocks of cancer biology, suggesting that studying them directly might provide new and actionable insights. Our study used proteogenomics—an approach that integrates genomics with comprehensive characterization of proteins and their modifications—to study more than 100 lung adenocarcinomas and normal lung tissues from the same patients. Our findings offer a deeper understanding of lung cancer biology, highlight opportunities for novel treatment approaches, and provide an important resource for scientists and clinicians studying and treating this challenging disease.

(Summary submitted by Michael Gillette, MD, PhD, Division of Pulmonary & Critical Care Medicine, Department of Medicine)


U.S. POSTOPERATIVE OPIOID PRESCRIBING RATES 
Opioids After Surgery in the United States Versus the Rest of the World: The International Patterns of Opioid Prescribing (iPOP) Multicenter Study
Kaafarani HMA, Han K, El Moheb M, Kongkaewpaisan N, Jia Z [et al.], Lillemoe KD.
Published in Annals of Surgery on July 9, 2020

The United States is in the midst of an unprecedented opioid epidemic. In this international collaborative, we compared the opioid prescribing patterns after surgery in the U.S. to that of seven other countries around the world. We showed that for the same surgical procedures performed, physicians in the US prescribed alarmingly high amounts of opioid medications upon discharge from the hospital compared to the rest of the world. For instance, 91% of U.S. patients were prescribed opioids compared to only 5% of non-U.S. patients. We also showed that the variation in opioid prescribing was substantially larger in the U.S. This striking difference highlights the need to seriously re-examine the culture of opioid prescribing in the U.S.

(Summary submitted by Mohamad El Moheb, MD, Department of Surgery)


A POTENTIAL THERAPEUTIC APPROACH TO HLRCC
Nitrogen Trapping as a Therapeutic Strategy in Tumors with Mitochondrial Dysfunction
Madala HR, Helenius IT, Zhou W, Mills E, Zhang Y [et al.], Yeh JJ.
Published in Cancer Research on July 10, 2020

The mitochondria is the powerhouse of a healthy animal cell. However, mitochondrial dysfunction in cancer cells, as caused by mutations or by a hypoxic microenvironment, has been linked to tumor virulence such as metastasis. For example, the mutations in hereditary leiomyomatosis and renal cell cancer (HLRCC), a familial cancer disorder, can disrupt mitochondrial metabolism, resulting in a very aggressive kidney cancer. Here, we describe a potential therapeutic approach against HLRCC and other types of cancers manifesting mitochondrial dysfunction by targeting their reliance on an enzyme called GOT1. This study demonstrates promising preclinical results in mouse models, warranting its future clinical investigations.

(Summary submitted by Jing-Ruey Joanna Yeh, PhD, Cardiovascular Research Center, Division of Cardiology, Department of Medicine)


MICROTUBULE COHERENCE AND IN VIVO TUMOR CELL DYNAMICS
In Vivo Microscopy Reveals Macrophage Polarization Locally Promotes Coherent Microtubule Dynamics in Migrating Cancer Cells
Luthria G, Li R, Wang S, Prytyskach M, Kohler RH [et al.], Miller MA.
Published in Nature Communications on July 14, 2020

As major cytoskeletal components, microtubules help orchestrate mitosis, cell migration, and are targets for anti-cancer drugs. Local interactions between cancer cells and surrounding tissue can influence microtubule behaviors and drug responses, but it has been challenging to directly observe their dynamics within native tumor environments. We developed an imaging pipeline to quantify microtubule dynamics in live tumor models, and surprisingly found that the wound-healing response of neighboring immune cells can be as much of a factor as the extracellular matrix in promoting coherent microtubule alignment thought to drive cancer metastasis.

(Summary submitted by Miles Miller, PhD, Center for Systems Biology and Department of Radiology, and Gaurav Luthria, BS, Center for Systems Biology)


PHASE I TRIAL OF BRAF INHIBITOR AND MEK INHIBITOR
A Phase 1b/2 Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAF V600E/K-mutant Solid Tumors
Sullivan RJ, Weber JS, Patel SP, Dummer R, Carlino MS [et al.], Ascierto PA.
Published in Clinical Cancer Research on July 15, 2020

This was a phase I trial of the BRAF inhibitor encorafenib and MEK inhibitor binimentinb that identified the appropriate dose of the combination for further testing in patients whose tumors were identified to have a mutation in a gene called BRAF.  We demonstrated activity in a number of settings, including patients with BRAF-mutant melanoma and BRAF-mutant colorectal cancer who previously were not treated with a BRAF inhibitor.  Based on these results, two larger trials were performed that led to the FDA-approval of this combination for the treatment of BRAF-mutant melanoma patients and this combination plus a third agent, called cetuximab, for patients with BRAF-mutant colorectal cancer.

(Summary submitted by Ryan J. Sullivan, MD, Division of Hematology/Oncology, Mass General Cancer Center and Department of Medicine)


DIFFERENTIATING NON-CELIAC GLUTEN SENSITIVITY FROM CELIAC DISEASE
Subclass Profile of IgG Antibody Response to Gluten Differentiates Non-Celiac Gluten Sensitivity from Celiac Disease
Uhde M, Caio G, De Giorgio R, Green PH, Volta U, Alaedini A.
Published in Gastroenterology on July 20, 2020

Our group previously demonstrated that non-celiac gluten/wheat sensitivity (NCGWS) is associated with elevated levels of IgG antibodies to gliadin (AGA). With this new study, we found that in comparison with celiac disease (CD), the subclass IgG AGA response in NCGWS is characterized by significantly lower levels of IgG1 and IgG3, and higher levels IgG4. Moreover, levels of IgG4 and IgG1 AGA correlated with circulating concentrations of intestinal fatty acid-binding protein (FABP2), a marker of intestinal epithelial cell damage. The data reveal significant differences between CD and NCGWS, indicating different mechanisms in the immune response to gluten. Furthermore, the correlation of the AGA IgG response with FABP2 expression is suggestive of a link between the antibodies and intestinal damage in NCGWS patients, paving the way to better understand the NCGWS pathogenesis.

(Summary submitted by Giacomo Pietro Caio, MD, PhD, MassGeneral Hospital for Children, Celiac Disease Center and Mucosal Immunology and Biology Research Center)


GENETIC RISK FOR OBESITY TIED TO WORKPLACE FOOD PURCHASES
Polygenic Risk Score for Obesity and the Quality, Quantity, and Timing of Workplace Food Purchases: A Secondary Analysis from the ChooseWell 365 Randomized Trial
Dashti HS, Hivert M, Levy D, McCurley JL, Saxena R, Thorndike AN.
Published in PLOS Medicine on July 21, 2020

Genetics play a role in the development of obesity, yet its influence on food choice behaviors is not well understood. We used workplace cafeteria purchasing data from 397 employees at Mass General to determine whether genetic risk for obesity is associated with purchasing behaviors. We observed that the highest quartile of a genome-wide polygenic score for BMI (highest genetic risk for obesity) was associated with lower dietary quality of all purchases, higher quantity of food purchases, later time of breakfast purchases, and lower likelihood of preparing dinner at home relative to the lowest quartile. These findings suggest that genetic risk for obesity may influence eating behaviors that contribute to weight.

(Summary submitted by Hassan Dashti, PhD, RD, Center for Genomic Medicine and Department of Anesthesia, Critical Care and Pain Medicine)


INSIGHTS INTO IMPROVING MALARIA VACCINES
Mapping Functional Humoral Correlates of Protection Against Malaria Challenge Following RTS,S/AS01 Vaccination
Suscovich TJ, Fallon JK, Das J, Demas AR, Crain J [et al.] Alter G.
Published in Science Translational Medicine on July 22, 2020

RTS,S/AS01 is the most advanced malaria vaccine candidate, showing 40%–80% protection in human challenge studies in malaria-naïve individuals. Using a comprehensive systems serological profiling platform, we identified the humoral correlates of protection against malaria and validated it across multiple challenge studies. More so than antibody concentration, qualitative functional humoral features robustly predicted protection from infection across vaccine regimens. Two antibody features, antibody-mediated phagocytosis and engagement of Fc gamma receptor 3A, were able to predict protection across an additional two human challenge studies. These may be used to guide rational design of an improved vaccine against malaria.

(Summary submitted by Rachel Leeson, MS, Ragon Institute of MGH, MIT and Harvard)

Press Releases

Clinicians Find Encouraging Results from Functional MRI in an Unresponsive Patient With COVID-19
Featuring Brian Edlow, MD, and Bruce Rosen, MD, PhD

Many patients with severe COVID-19 remain unresponsive after survival. A team at Mass General now describe a patient with severe COVID-19 who demonstrated functionally intact brain connections and weeks later recovered the ability to follow commands.


New Studies with Sean M. Healey & AMG Center for ALS at Mass General Target Disease-causing Gene

New Mass General studies focus on the SOD1 gene in ALS.


Groundbreaking Mass General-Designed Cancer Cell-sorting Chip Brings Liquid Biopsies Closer to Clinic
Featuring Avanish Mishra, PhD, Taronish Dubash, PhD, and Mehmet Toner, PhD

A new cancer cell sorting chip developed by Mass General investigators could improve the accuracy of liquid biopsies by 100-fold.


Hospital’s Addiction Consult Team Helps Reduce Readmissions for Patients with Substance Use Disorders
Featuring Sarah Wakeman, MD

A recent study reveals that hospitalized patients with substance use disorders who are seen by an addiction consult team are less likely to be readmitted to the hospital within a month after discharge.


Initial Data from the Landmark REPRIEVE Study on HIV and Heart Disease Highlights the Multiple Health Risks Among a Population That’s Living Longer
Featuring Steven Grinspoon, MD

A suite of articles in The Journal of Infectious Diseases contain the first swath of important data from the world’s largest study of cardiovascular disease prevention in people with HIV.


Mass General Hospital Redefines Neurologic Therapy with Implementation of New Deep Brain Stimulation Device
Featuring Todd Herrington, MD, PhD

In a shift to personalize treatment for neurological disease, a team of neurologists and neurosurgeons from Mass General completed the first deep brain stimulation implant in New England that will be able to use the patient’s own brain activity to guide therapy.


Mass General Hospital Study Finds No Relationship Between Blood Type and Severity of COVID-19
Featuring Anahita Dua, MBChB, MBA, MSc

Mass General researchers have reported blood type is not associated with a severe worsening of symptoms in people who have tested positive for COVID-19, dispelling previous reports that suggested a correlation between certain blood type and COVID-19.


New Study Identifies the Missing Piece Needed for Lower-cost, High-quality MRI Scans
Featuring Matthew Rosen, PhD

In a study published in Science Advances, a researcher at Mass General and colleagues in Australia identify the missing piece needed to generate high-quality imaging using low-cost MRI scanners, which could expand the role of this powerful technology in medicine.


Range of COVID-19 Skin Signs Linked to Disease Severity
Featuring Esther Freeman, MD, PhD

Researchers at Mass General and Harvard Medical School, in collaboration with the American Academy of Dermatology and International League of Dermatologic Societies, have created an international registry for describing and cataloging the broad spectrum of dermatologic manifestations associated with coronavirus infections.


New CRISPR C-to-G DNA Base Editor Expands the Landscape of Precision Genome Editing
Featuring Julian Grünewald, MD, and J. Keith Joung, MD, PhD

New genome-editing technologies developed by researchers in J. Keith Joung’s laboratory have the potential to help understand disease-associated genetic mutations that are based on C-to-G (cytosine to guanine) single base changes.

Blog Posts

Five Things to Know: Reducing the Traumatizing Effects of “Air Hunger” in Mechanically Ventilated Patients
Featuring Christopher M. Worsham, MD

How medical treatment for air hunger can reduce the distressing feeling of needing more air than you are able to take in.


Martinos Researchers Share Their Favorite Recipes

Enjoying the summer at home this year and looking for a new recipe? Try taking a page out of the Martinos Cookbook!


Five Things to Know About COVID-19 and Intimate Partner Violence
Featuring Eve Valera, PhD

When a person is infected with COVID-19, the first thing a physician will advise is to self-isolate and stay home. But what if home isn't safe?


Share Your Research Story with an Image in the 2020 MGRI Image Contest

The MGRI Image Contest provides an opportunity for scientists to share their best research images, stories and unique points of view with colleagues and science fans across the globe.


Survey Shows A Worrisome Rise in Mental Health Issues Related to the COVID-19 Pandemic
Featuring Sarah Gray, PsyD

A nationwide study co-led by Mass General researchers found high levels of worry, frustration, boredom and anxiety.


Five Things to Know About the Ragon Institute
Featuring Bruce Walker, MD

The Ragon Institute of MGH, MIT and Harvard is a leading institution in infectious disease and immunology research. Here are five things to know.


Mass General Clinician-Researchers Share Firsthand Experiences with COVID-19 Surge

Mass General investigators who are co-affiliated with the Broad Institute discuss patient care and the hospital’s response to COVID-19.