Snapshot of Science for January 2022

Welcome to our Snapshot of Science for January 2022

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:

15 new studies published in high-impact journals, along with 9 summaries submitted by the research teams
15 new research-related press releases from the Mass General Public Affairs office
3 posts from the Mass General Research Institute blog

Publications

Depression and COVID-19 Vaccine Information
Association of Major Depressive Symptoms With Endorsement of COVID-19 Vaccine Misinformation Among US Adults
Perlis RH, Ognyanova K, Santillana M, Lin J, Druckman J [et al.], Della Volpe J
Published in JAMA Network Open on Friday, January 21, 2022 | *Summary available | Press Release

Measuring pH and Calcium Ions in Different Tissue Types
Quantification of Bone Marrow Interstitial pH and Calcium Concentration by Intravital Ratiometric Imaging
Yeh SA, Hou J, Wu JW, Yu S, Zhang Y [et al.], Lin CP
Published in Nature Communications on Wednesday, January 19, 2022 | *Summary available

Kinase Signaling in Metastatic Prostate Cancer Varies by Location
Differential Kinase Activity Across Prostate Tumor Compartments Defines Sensitivity to Target Inhibition
Karabacak NM, Zheng Y, Dubash TD, Burr R, Micalizzi DS [et al.], Maheswaran S
Published in Cancer Research on Wednesday, January 19, 2022 | *Summary available

Sugar Chains in the Brain Are Surprisingly Simple
Mammalian Brain Glycoproteins Exhibit Diminished Glycan Complexity Compared to Other Tissues
Williams SE, Noel M, Lehoux S, Cetinbas M, Xavier RJ [et al.], Mealer RG
Published in Nature Communications on Wednesday, January 12, 2022 | *Summary available

A Novel Target for Antifibrotic Therapeutic Development
Hepatitis B and Hepatitis C Virus Infection Promote Liver Fibrogenesis through a TGF-β1-induced OCT4/Nanog Pathway
Li W, Duan X, Zhu C, Liu X, Jeyarajan AJ [et al.], Lin W
Published in Journal of Immunology on Wednesday, January 12, 2022 | *Summary available

Changes Induced by Retinoblastoma Tumor Suppressor Protein
Active RB Causes Visible Changes in Nuclear Organization
Krishnan B, Yasuhara T, Rumde P, Stanzione M, [et al], Dyson NJ
Published in Journal of Cell Biology on Wednesday, January 12, 2022 | *Summary available

Participation Differences by Gender in Academic Medicine Classrooms
Gender Differences in the Amount and Type of Student Participation During In-Person and Virtual Classes in Academic Medicine Learning Environments
Cromer SJ, D'Silva KM, Phadke NA, Lord E, Rigotti NA, Baer HJ
Published in JAMA Network Open on Wednesday, January 12, 2022 | *Summary available | Press Release

Booster-Induced Immunity to Omicron
mRNA-based COVID-19 Vaccine Boosters Induce Neutralizing Immunity Against SARS-CoV-2 Omicron Variant
Garcia-Beltran WF, St Denis KJ, Hoelzemer A, Lam EC, Nitido AD [et al.], Balazs AB
Published in Cell on Thursday, January 6, 2022 | Press Release

Insights from Congenital Hydrocephalus
Brain Ventricles as Windows Into Brain Development and Disease
Duy PQ, Rakic P, Alper SL, Butler WE, Walsh CA [et al.], Kahle KT
Published in Neuron on Wednesday, January 5, 2022

COVID-19 Vaccine Response in Cancer Patients
Neutralization Breadth of SARS-CoV-2 Viral Variants Following Primary Series and Booster SARS-CoV-2 Vaccines in Patients With Cancer
Naranbhai V, St Denis KJ, Lam EC, Ofoman O [et al.], Iafrate AJ; CANVAX team
Published in Cancer Cell on Wednesday, January 5, 2022

Regulation of Symmetric Divisions in Adult Hippocampal Neural Stem Cells
Transcriptional Regulation of Neural Stem Cell Expansion in Adult Hippocampus
Guo N, McDermott KD, Shih YT, Zanga H, Ghosh D [et al.] , Sahay A
Published in Elife on Tuesday, January 4, 2022 | *Summary available

Female Authorship in Surgery
Trends in Female Authorship in High Impact Surgical Journals Between 2008 and 2018
Hart KL, Boitano LT, Tanious A, Conrad MF, Eagleton MJ [et al.], Srivastava SD
Published in Annals of Surgery on Saturday, January 1, 2022

A Platform for Rapidly Developing Patient-specific APECs
Antibody-Peptide Epitope Conjugates for Personalized Cancer Therapy
Zhang S, Yan C, Millar DG, Yang Q, Heather JM [et al], Cobbold M
Published in Cancer Research on Wednesday, December 29, 2021

A New Technique to Generate Human Reporter Cell Lines
TRACE Generates Fluorescent Human Reporter Cell Lines to Characterize Epigenetic Pathway
Tchasovnikarova I, Marr S, Damle M, Kingston R
Published in Molecular Cell on Thursday, December 16, 2021

Diversity Efforts Are Falling Short in Cancer Care
Diversity Trends by Sex and Underrepresented in Medicine Status Among US Radiation and Medical Oncology Faculty Over 5 Decades
Kamran SC, Niemierko A, Deville C Jr, Vapiwala N
Published in JAMA Oncology on Thursday, December 9, 2021 | *Summary available

Publication Summaries

Our team examined responses from 15,464 adults from across the US who completed a questionnaire on depression symptoms followed by an internet survey that included questions about statements related to COVID-19 vaccination. We found that participants with moderate or greater major depressive symptoms were more likely to endorse at least one of four false statements about COVID-19 vaccines on the subsequent survey, and those who endorsed these statements were less likely to be vaccinated. Specifically, the presence of depression was associated with a 2.2-times higher likelihood of endorsing misinformation, and respondents endorsing at least one misinformation statement were half as likely to be vaccinated and 2.7 times more likely to report vaccine resistance.

Hematopoietic stem cells (HSCs) reside in the bone marrow, surrounded by bone where 99% of the calcium in the body is stored and released during constant bone remodeling. Extracellular [Ca2+] can regulate HSC behavior but no technique exists to quantify the [Ca2+] distribution inside the bone marrow. We developed an intravital ratiometric imaging technique and found, unexpectedly, that the mean bone marrow [Ca2+] is not different from serum, while the HSCs are maintained in locations with slightly elevated [Ca2+]. With appropriate sensors, the tool can be broadly applied to measuring both pH and [Ca2+] in multiple tissue types.

(Summary submitted by Shu-Chi (Allison) Yeh, PhD, of the University of Rochester School of Medicine and Dentistry)

Metastatic prostate cancer remains incurable. We studied the expression of kinases at the single cell level across tumors residing at different sites in mouse models of prostate cancer. Despite originating from the same primary tumor, metastases in the lung, liver, and bone exhibited differences in kinase signaling, with bone metastasis exhibiting the highest levels of activity, specifically the PI3K/mTOR pathway. Further, within the tumors themselves, epithelial cancer cells had higher levels of this kinase compared with mesenchymal tumor cells rendering these populations more sensitive to drugs targeting this pathway. Such heterogeneity within and across tumors should be considered when choosing therapies to treat prostate cancer patients.

(Summary submitted by Murat Karabacak, PhD, from the Center for Engineering in Medicine & Surgery)

Nearly all cells in our body decorate their surfaces with chains of sugars in a process called glycosylation. This is especially important in the brain, where small changes to the sugar chains contribute to conditions including epilepsy and mental health. In this study we performed detailed characterization of sugar chains in the brain, finding that, despite their importance, they are surprisingly more simple than other tissues. These findings generate a roadmap for future work of glycosylation in brain health and disease.

(Summary submitted by Robbie Mealer, MD, PhD, of the Psychiatric and Neurodevelopmental Genetics Unit)

Infection with hepatitis B (HBV) and hepatitis C virus (HCV) are primary causes of progressive liver scarring and liver cancer worldwide and thus are associated with significant morbidity and mortality. Octamer binding transcription factor 4 (OCT4) and Nanog are direct targets of the TGF-β1 signaling cascade, which is a main driver of liver scarring, also known as fibrosis. We demonstrated that HBV, HCV, and HBV/HCV co-infection/co-exposure in hepatocytes, the main cells in the liver and a scar forming cell type known as hepatic stellate cells (HSCs), induce scar formation through the TGF- β1/OCT4/Nanog pathway. These findings provide new and exciting evidence that OCT4/Nanog may be a novel target(s) for antifibrotic therapeutic development.

(Summary submitted by Wenyu Lin, PhD, from the Division of Gastroenterology)

The retinoblastoma tumor suppressor protein (RB) inhibits cell cycle progression by blocking E2F-dependent transcription. Here, we show that RB activation also induces visible changes in nuclear organization that appear as chromatin dispersion in both euchromatin and heterochromatin regions. Surprisingly, this activity of RB is independent of E2F. Dispersion occurs after cell cycle arrest, requires other known partners of RB and it is associated with specific forms of active RB. Gene expression profiles revealed that the dispersion phenotype correlates with increased autophagy. We infer that, after cell cycle arrest, RB changes nuclear organization and influences cellular state transitions.

(Summary submitted by Nick Dyson, PhD, of the Mass General Cancer Center)

Our research team observed students (primarily physicians-in-training) during large, lecture-based classes and smaller, discussion-based classes for two weeks in July 2019 (in-person) and six weeks in July-August 2020 (virtual). We found that women both asked and answered fewer questions than men in large, in-person classes, but that these differences were not seen in small classes and were decreased in virtual classes. We also found that women used more deferential language (e.g., “Sorry if I missed this”) than men when asking questions in large classes. These findings suggest that participation-based evaluations may disproportionally disadvantage women, resulting in gender bias, and show that smaller and virtual classes may lead to more equitable participation.

(Summary submitted by Sara Cromer, MD, from the Department of Medicine)

Learning or enriching stimuli activate neural stem cells in the hippocampus of adult mammals and promote asymmetric divisions to make more new neurons and glial cells. During unfavorable conditions such as chronic stress or aging, stem cells stay quiescent or undergo symmetric divisions and amplify in number. Symmetric divisions prevent premature neurogenesis while “anticipating” future neurogenic demands. Here, we identify Kruppel-like factor 9 (Klf9) as a regulator of symmetric divisions of adult hippocampal neural stem cells. Targeting Klf9-dependent mechanism to expand the neural stem cell pool may harbor potential for brain repair in aging and in Alzheimer’s disease.

(Summary submitted by Amar Sahay, PhD, of the Center for Regenerative Medicine)

While diversity rates of radiation oncology (RO) and medical oncology (MO) faculty have increased over the past five decades — most notably for women — they have not kept pace with the changing demographics of the U.S. population, particularly in groups considered underrepresented in medicine (URM). Our study found that women represent half of the US population but are still underrepresented at the faculty and leadership levels. Black, Hispanic and Indigenous individuals represent 31% of the population but only about 5% of faculty in RO and MO, highlighting the need for more aggressive diversity and inclusion efforts.

(Summary submitted by Sophia Kamran, MD, of the Mass General Cancer Center and Department of Radiation Oncology)

Press Releases

Randomized Controlled Trial Offers Insights on How the Timing of Dinner and Genetics Affect Individuals’ Blood Sugar Control
Featuring Richa Saxena, PhD, from the Center for Genomic Medicine

Blood sugar control, which is impaired in individuals with diabetes, is affected by various factorsincluding the timing of meals relative to sleep as well as levels of melatonin, a hormone primarily released at night that helps control sleep-wake cycles.

Undiagnosed Autistic Traits Common Among Youths with Substance Use Disorders
Featuring James McKowen, PhD, from the Center for Addiction Medicine

One in five teens and young adults who seek treatment for alcohol or drug use may have traits characteristic of a previously unrecognized autism spectrum disorder, researchers at Mass General report.

People Who Are Depressed May Be More Susceptible to Misinformation About COVID-19 Vaccines
Featuring Roy H. Perlis, MD, MSc, from the Center for Quantitative Health

A general bias toward negativity — or the tendency to focus on negative rather than positive information — may exacerbate the spread of misinformation. Because depression may contribute to such negativity bias, a team led by investigators at Mass General examined whether people who experience depressive symptoms may be more receptive to misinformation related to COVID-19 vaccines.

Newly Discovered DNA Repair Mechanisms Point to Potential Therapy Targets for Cancer and Neurodegenerative Diseases
Featuring Raul Mostoslavsky, MD, PhD, from the Mass General Cancer Center

Mass General investigators and colleagues have developed high-throughput microscopy and machine learning systems that can identify and classify DNA repair factors.

Women and Men Physicians Participate Differently in Academic Settings, Potentially Contributing to Gender Biases in Evaluations That Disadvantage Women
Featuring Sara J. Cromer, MD, from the Department of Medicine

In large, in-person academic classrooms composed predominantly of physicians in the fellowship stage of training, women were less likely to ask and answer questions than men and were more likely to use deferential language.

Mathematical Model May Help Improve Treatments and Clinical Trials of Patients With COVID-19 and Other Illnesses
Featuring Lance Munn, PhD, and Rakesh Jain, PhD, of the Edwin L. Steele Laboratories

Investigators who recently developed a mathematical model that indicated why treatment responses vary widely among individuals with COVID-19 have now used the model to identify biological markers related to these different responses.

First Study to Detect Delta Variant of SARS-CoV-2 in Maternal Bloodstream and Placenta in Cases of Stillbirth and Pregnancy Complications
Featuring Andrea Edlow, MD, MSc, from the Vincent Center for Reproductive Biology

A growing body of evidence has linked the Delta variant of SARS-CoV-2 with an increased risk for pregnancy complications, including stillbirths. Now, for the first time, researchers at Mass General and Brigham and Women’s Hospital have detected the Delta variant in the blood and placentas of women who had stillbirths and serious pregnancy complications.

Study May Help Clinicians Use Sleep Brain Wave Patterns to Diagnose Dementia and Other Forms of Cognitive Impairment
Featuring Haoqi Sun, PhD, from the Department of Neurology

Sleep spindles, bursts of brain activity that occur during sleep, relate to cognitive function and can be measured through automated methods, but no consensus exists for determining which sleep spindle parameters are important.

Skin-related Side Effects Indicate Better Prognosis for Patients Taking Certain Cancer Drugs
Featuring Yevgeniy R. Semenov, MD, from the Department of Dermatology

Immune checkpoint inhibitors, which strengthen the immune response against tumor cells, have become standard of care for many patients with advanced cancers; however, the medications can often cause side effects, most commonly affecting the skin.

Brain-based Method to Determine Impairment from Cannabis Intoxication is Reported by Researchers
Featuring Jodi Gilman, PhD, of the Center for Addiction Medicine

Researchers at Mass General have found a noninvasive brain imaging procedure to be an objective and reliable way to identify individuals whose performance has been impaired by THC, the psychoactive ingredient in cannabis.

Booster Dose of mRNA COVID-19 Vaccine is Required for Immune Protection Against Omicron Variant of SARS-CoV-2
Featuring Alejandro Balazs, PhD, from the Ragon Institute of MGH, MIT and Harvard

An additional “booster” dose of Moderna or Pfizer mRNA-based vaccine is needed to provide immunity against the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, according to a study by researchers at the Ragon Institute of MGH, MIT and Harvard. The results of this study, indicate that traditional dosing regimens of COVID-19 vaccines available in the United States do not produce antibodies capable of recognizing and neutralizing the Omicron variant.

Mass General Neuroendovascular Program Reports Real-world Results on the Use of a New Device to Treat Brain Aneurysms
Featuring Adam A. Dmytriw, MD, MPH, MSc

A recent international study led by researchers at Mass General and other institutions offers real-world results on the use of a novel device for treating brain aneurysms, or balloon-like bulges on weakened blood vessels that can rupture to cause life-threatening bleeding.

The HEALEY ALS Platform Trial Achieves Enrollment Goal for its Fourth Regimen (Pridopidine)
Featuring Merit Cudkowicz, MD, MSc, from the Department of Neurology

The HEALEY ALS Platform trial led by the Northeast ALS Consortium (NEALS) and the Healey & AMG Center for ALS at Mass General is paving the way for rapid testing of potential treatments for people with amyotrophic lateral sclerosis (ALS).

Study Shows Troubling Lack of Knowledge by Physicians about the Americans with Disabilities Act
Featuring Lisa I. Iezzoni, MD, MSc, from the Mongan Institute Health Policy Center

More than 30 years after the passage of the Americans with Disabilities Act (ADA), most physicians still lack basic knowledge about “reasonable accommodations” the law requires them to provide to people with disabilities, a study by researchers at Mass General have found.

Gene Involved in Sense of Smell Could Play a Role in the Spread of Breast Cancer to the Brain
Featuring Bakhos Tannous, PhD, from the Department of Neurology

An olfactory receptor gene that aids in the sense of smell may also play a role in the metastasis of breast cancer to the brain, bones and lung, researchers from Mass General have found.

Blog Posts

Scholars Program Seeks to Reduce Health Disparities by Empowering a Diverse Workforce
Featuring Gaurdia Banister, RN, PhD, NEA-BC, FAAN, of the Munn Center for Nursing Research

The Connell-Jones Endowed Chair Diversity Research Scholars Program was established by the Yvonne L. Munn Center for Nursing Research to support, educate and mentor culturally diverse nurses who are interested in research related to health equity and health disparities.

Mass General Gastroenterology and Tufts University Receive NIH Funding to Study Individual Responses to Food and Dietary Patterns
Featuring Hamed Khalili, MD, MPH, from the Division of Gastroenterology

“This is an incredibly ambitious project that has the potential to transform the field of nutrition science,” says Hamed Khalili MD, MPH, a gastroenterologist who is leading the Mass General research team. “The wealth of collected data will ultimately allow us to personalize dietary recommendations to optimize health outcomes.”

Study Finds More Efforts Are Needed to Increase Diversity Among Cancer Clinicians
Featuring Sophia Kamran, MD, from the Mass General Cancer Center

While diversity rates of radiation oncology and medical oncology faculty have increased over the past five decades — most notably for women — they have not kept pace with the changing demographics of the U.S. population, particularly in groups considered underrepresented in medicine.

The Mass General Difference

Conditions & Treatments

Patients & Visitors

Research & Innovation

Mass General
Research Institute

Snapshot of Science for January 2022