RABID-Seq: A New Method Combines Barcoded Viral Tracing with Single-Cell RNA Sequencing

Cells do not act in isolation. Rather, cells interact which each other to control the physiology and pathology of the central nervous system (CNS). Current approaches that can profile individual CNS cells cannot profile cell interactions, which means they can fail to detect key interactions that may involve just a small subset of cells. Francisco J. Quintana, PhD, a principal investigator in the Ann Romney Center for Neurologic Diseases, and team developed a novel virus-based method to barcode cell interactions in vivo. Their technique allowed them to study cell interactions at single cell resolution, to identify novel physiologic mechanisms and targets for therapeutic intervention. This novel virus-based method is called RABID-seq.

“We used this new method to identify novel targets to treat neurodegeneration,” said Quintana. “With RABID-seq, we’ve uncovered novel physiological mechanisms and candidate therapeutic targets associated with neuronal disorders such as autoimmune encephalomyelitis and multiple sclerosis.”

Read more in Science.

Medicaid Expansion Alone Does Not Resolve Disparities in Cancer Care

A new analysis of National Cancer Database records conducted by Brigham researchers indicates that while individuals experienced accelerated treatment timelines after the Affordable Care Act, overall, hospitals that primarily serve minorities did not improve average delivery times for cancer treatments. The findings point toward the need for additional reforms to support delivery of care in under-funded health systems.

“Providing people with insurance doesn’t necessarily ensure that they will get the care they deserve,” said corresponding author Quoc-Dien Trinh, MD, of the Division of Urologic Surgery. “This project reminds stakeholders and policymakers that there’s downstream work that has to be done beyond expanding coverage, whether in patient navigation or in making sure that people can afford to miss work to receive care when they need it.”

Read more in JCO Oncology Practice and in a Brigham research brief.

Key Steps Could Reduce Cases and Deaths from Rheumatic Heart Disease in the African Union

Rheumatic heart disease (RHD) remains a major cause of cardiovascular disease in Africa, even as acute rheumatic fever and RHD have become rare in high-income countries. In a new study led by Brigham investigators, a team modeled the investment case for control of RHD in the African Union (AU) region. Results showed the potential to reduce RHD death by almost a third by increasing coverage of RHD interventions in regions of the AU through 2030, with a high return on investment in both the long and short term.

“Investing in early detection of rheumatic fever and rheumatic heart disease and providing cardiac surgery to those who need it could have a dramatic effect, saving around 70,000 lives by 2030,” said corresponding author Gene Bukhman, MD, PhD, of the Division of Cardiovascular Medicine and Division of Global Health Equity.

Read more in Lancet Global Health and in a Brigham research brief.

Asthma Attacks Plummeted Among Black and Hispanic/Latinx Individuals During the COVID-19 Pandemic

When the COVID-19 pandemic swept over the United States, a series of reports suggested that fewer people were coming to emergency departments for all sorts of medical problems, including asthma attacks and even heart attacks. In the case of asthma, it was not clear if the drop was due to people avoiding emergency services or due to better asthma control. A new analysis from Brigham investigators shines new light on this question.  In a report of data collected as part of a trial in Black and Hispanic/Latinx patients with asthma that began before COVID-19 hit the U.S., they found total asthma attacks decreased by greater than 40 percent with the onset of the pandemic. Results are published in

“We found a substantial decrease in asthma exacerbation — on the order of what we see for biologic therapies for severe asthma,” said lead author Justin Salciccioli, MBBS, MA, a fellow in the Division of Pulmonary and Critical Care Medicine at the Brigham. “Although we don’t know for sure who in the cohort changed their behavior, it’s likely that decreased exposure to environmental or viral triggers contributed to our findings.”

Read more in The Journal of Allergy & Clinical Immunology: In Practice and in a Brigham research brief.

Discovery of Genetic Drivers Linked to Progression in Parkinson’s Disease

A key driver of patients’ well-being and clinical trials for Parkinson’s disease (PD) is the course the disease takes over time. However, nearly all that is known about the genetics of PD is related to susceptibility — a person’s risk for developing the disease in the future. A new study by Brigham investigators uncovers the genetic architecture of progression and prognosis, identifying five genetic locations (loci) associated with progression. The team also developed the first risk score for predicting progression of PD over time to dementia, a major determinant of quality of life.

“The patients who come to see me in the clinic are concerned about their future, rather than their past risk factors,” said corresponding author Clemens Scherzer, MD, the director of the Center for Advanced Parkinson Research at the Brigham and director of the Brigham Precision Neurology Program. “They want to know how they will be doing in the future and need medications designed to stop the disease from rapidly progressing. This is the central question in our study: Which genes determine whether a patient will have an aggressive or benign course, and which variants influence who will develop dementia?”

Read more in Nature Genetics and in a Brigham research brief.

3D ‘Lung-on-a-Chip’ Model of Human Alveolar Lung Tissue Developed to Test New Therapies for COVID-19 and Other Lung Conditions

Tight junction expressions between cells in an alveolar sac-like structure in our model

To better understand respiratory diseases and develop new drugs faster, Brigham investigators designed a 3D “lung-on-a-chip” model of the distal lung and alveolar structures, the tiny air sacs that take in oxygen as you breathe. With this innovation, researchers are actively studying how COVID-19 viral particles travel through airways and impact pulmonary cells. Notably, this technology enables scientists to investigate how various COVID-19 therapies, such as remdesivir, impact the replication of the virus.

“We believe that it is a true innovation,” said Y. Shrike Zhang, PhD, associate bioengineer in the Brigham’s Department of Medicine and Division of Engineering in Medicine. “This is a first-of-its-kind in vitro model of the human lower lung that can be used to test many of the biological  mechanisms and therapeutic agents, including anti-viral drugs for COVID-19 research.”

Read more in Proceedings of the National Academy of Sciences USA and in a Brigham research brief.

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