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Different activity in two molecular networks could help explain why triple negative breast cancers tend to be more aggressive in African American (AA) women compared with white American (WA) women, a new study led by Johns Hopkins Kimmel Cancer Center researchers suggests.
The findings, published online Dec. 20 in eLife, may explain the marked racial disparity in mortality for this subset of breast cancer and offer new strategies for treating this deadly disease.
“The incidence of breast cancer in African American women is lower than in white American women, but mortality is higher. Our work shows the molecular mechanisms that cause cancer cells to grow and spread faster in African American women,” says study leader Dipali Sharma, Ph.D., professor of oncology at the Johns Hopkins University School of Medicine and John Fetting Fund for Breast Cancer Prevention researcher.
Better diagnosis and treatment have decreased breast cancer mortality in the past few decades, cutting death rates by about 40%, but AA women are still 42% more likely to die from this disease than WA women. Although AA women have a lower incidence of breast cancer than WA women overall, the disparity in mortality can be partially explained by a higher incidence among AA women of triple negative breast cancer, an aggressive breast cancer subset characterized by a lack of estrogen, progesterone and HER2 receptors. However, even among triple negative breast cancers, those in AA women tend to be even more aggressive than those in WA women, significantly decreasing AA survival rates.
To better understand this phenomenon, Sharma and her colleagues compared the behavior of triple negative breast cancer cell lines isolated from AA and WA women. When grown in petri dishes, the cells from AA women multiplied at a faster pace, were more invasive to surrounding tissue, were more likely to migrate, and had more “stem-like” cells capable of creating new tumors compared with the cells from WA women. When placed into mice, the cells from AA women created larger tumors faster and metastasized quicker compared with the cells from WA women.
“The triple negative breast cancer cells from African American women were more aggressive from the get-go,” says Sumit Siddharth, first author on the paper and postdoctoral fellow at Johns Hopkins Medicine.
Searching for the molecular mechanisms behind these differences, the researchers assessed gene activity in each of the cell lines and in tumor samples from AA and WA women. They found that two genes, known as GLI1 and Notch1, were more active in cells isolated from AA women compared with those isolated from WA women. Both genes produce proteins known as transcription factors, explains Sheetal Parida, a study co-author and postdoctoral fellow, and are responsible for regulating large networks of other genes that can broadly affect cell function.
To determine whether GLI1 and Notch1 could serve as effective targets for triple negative breast cancers, the researchers dosed the cell lines from WA and AA women with an inhibitor for each of these two genes along with a common chemotherapy agent used to treat these cancers. Although each agent was largely ineffective on its own, combining all three drugs significantly inhibited growth, invasion and migration in the AA cell lines. Treating mice with tumors grown from these cell lines had similar positive effects, reducing tumor size and metastasis.
Sharma says that she and her team plan to continue to test GLI1 and Notch1 inhibitors in mouse models of triple negative breast cancers to find the best combination with chemotherapies and eventually investigate this strategy in clinical trials of patients with this disease subtype.
“Eventually,” she says, “we may be able to close the survival gap between African American and white American women with triple negative breast cancers.”
In addition to Sharma, Siddharth and Parida, other researchers who contributed to this study were Nethaji Muniraj, Arumugam Nagalingam, David Lim, and Chenguang Wang from Johns Hopkins; Shawn Hercules and Juliet Daniel from MacMaster University, Hamilton, Canada; and Balazs Gyorffy from MTA TTK Momentum Cancer Biomarker Research Group, Budapest, Hungary.
This research was funded by the National Cancer Institute (R01CA204555).

About 1 in 44 children in the U.S. are diagnosed with autism spectrum disorder (ASD) by the age of 8, according to the 2018 Centers for Disease Control and Prevention surveillance. How a child’s DNA contributes to the development of ASD has been more of a mystery. Recently, clinicians and scientists have looked more closely at new, or de novo, DNA changes, meaning they only are present in affected individuals but not in the parents. Researchers have seen that these changes could be responsible for about 30% of ASD. However, which de novo variants play a role in causing ASD remains unknown.
Researchers at Baylor College of Medicine and Texas Children’s Hospital have taken a new approach to looking at de novo ASD genetic variants. In this multi-institutional study published in the journal Cell Reports, they applied sophisticated genetic strategies in laboratory fruit flies to determine the functional consequences of de novo variants identified in the Simons Simplex Collection (SSC), which includes approximately 2,600 families affected by autism spectrum disorder. Surprisingly, their work also allowed them to uncover a new form of rare disease due to a gene called GLRA2.
“ASDs include complex neurodevelopmental conditions with impairments in social interaction, communication and restricted interests or repetitive behaviors. In the current study, we initiated our work based on information from a cohort of ASD patients in the SSC whose genomes and those of their families had been sequenced,” said co-corresponding author Dr. Shinya Yamamoto, assistant professor of molecular and human genetics and of neuroscience at Baylor and investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s. “Our first goal was to identify gene variants associated with ASD that had a detrimental effect.”
The team worked with the fruit fly lab model to determine the biological consequences of the ASD-associated variants. They selected 79 ASD variants in 74 genes identified in the SSC and studied the effect of each ASD-linked gene variant compared to the commonly found gene sequence (reference) as a control, from three different perspectives.
Co-first author, Dr. Paul Marcogliese, postdoctoral fellow in Dr. Hugo Bellen’s lab, coordinated the effort on knocking out the corresponding fly gene, and examining their biological functions and expression patterns within the nervous system. They then replaced the fly gene with the human gene variant identified in patients, or the reference sequence, and determined how it affected biological functions in the flies.
Working with fruit flies carrying either the reference human gene or the variant forms, co-first author Dr. Jonathan Andrews, postdoctoral fellow in Dr. Michael Wangler’s lab at Baylor, was the point person investigating how these gene variants affected fly behavior. As ASD patients exhibit patterns of repetitive behavior as well as changes in social interaction, he evaluated the effect of the patient variants on an array of social and non-social fly behaviors, such as courtship and grooming. “It’s interesting to see that manipulation of many of these genes also can cause behavioral changes in the flies,” Andrews said. “We found a number of human genes with ASD variants that altered behavior when expressed in flies, providing functional evidence that these have functional consequences.”
The third approach involved overexpressing the genes of interest in different tissue types in fruit flies. Co-first authors Samantha Deal and Michael Harnish, two graduate students in Baylor’s Graduate Programs in Developmental Biology and Genetics and Genomics, respectively, working in Dr. Yamamoto’s lab, headed these studies. “While some gene variants may lead to conditions because they produce defective proteins, others may lead to disease because they cause overabundance or aberrant function of a particular protein, which can disrupt biological processes. We investigated whether overexpressing gene variants found in individuals with ASD might explain the detrimental effect for some of these genes,” Deal said.

Mayo Clinic researchers say senolytic drugs can boost a key protein in the body that protects older people against aspects of aging and a range of diseases. Their findings, which are published in eBioMedicine demonstrate this in mice and human studies.
Senolytics developed at Mayo Clinic and given once clear the bloodstream of senescent or “zombie” cells. These cells contribute to multiple diseases and negative aspects of aging. This study shows that the removal of senescent cells significantly boosts the production of a protective protein called a-klotho.
“We show that there is an avenue for an orally active, small-molecule approach to increase this beneficial protein and also to amplify the action of senolytic drugs,” says James Kirkland, M.D., Ph.D., a Mayo Clinic internist and senior author of the study.
The researchers first showed that senescent cells decrease levels of a-klotho in three types of human cells: umbilical vein endothelial cells, kidney cells and brain cells. They also demonstrated that using the senolyitics desatinib plus quercitin in three types of mice that a-klotho was increased. And then after administering desatinib plus quercitin in clinical trial participants with idiopathic pulmonary fibrosis, that a-klotho also increased.
“We also are first to link the potential impact of fat-resident senescent cells on brain a-klotho,” says Yi Zhu, Ph.D., a Mayo Clinic physiologist and biomedical engineer, and first author of the study. “This may open another avenue to investigate the impact of peripheral senescent cells on brain aging.”
The protein a-klotho is important to maintaining good health, as it tends to decrease with age, and especially decreases in multiple diseases, including Alzheimer’s, diabetes and kidney disease. Animal studies have shown that decreasing a-klotho in mice shortens life span and increasing a-klotho in mice by inserting a gene that causes its production increases life span by 30%.
Discovering ways to increase a-klotho in humans has been a major research goal, but that has been difficult because of its size and instability. Introducing it directly is problematic, as it would have to be administered into a vein instead of by mouth.
This study shows that senolytics, which can be administered orally, increase a-klotho in humans with idiopathic pulmonary fibrosis, a senescence-associated disease that leads to frailty, serious breathing difficulties and death.
The study was supported by the National Institute of Health, the Translational Geroscience Network, Robert and Arlene Kogod, the Connor Group, Robert J. and Theresa W. Ryan, and the Noaber Foundation.
The other authors are Yi Zhu, Ph.D.; Larissa Prata, Ph.D.; Erin Wissler Gerdes; Jair Machado Espindola Netto, Ph.D.; Tamar Pirtskhalava, Ph.D.; Nino Giorgadze; Utkarsh Tripathi; Christina Inman; Kurt Johnson; Ailing Xue; Allyson Palmer, M.D., Ph.D.; Tingjun Chen, M.D., Ph.D.; Kalli Schaefer; Jun Chen, Ph.D.; Sundeep Khosla, M.D.; Diana Jurk, Ph.D.; Marissa Schafer, Ph.D.; and Tamar Tchkonia, Ph.D. — all of Mayo Clinic — and Jamie Justice, Ph.D., and Stephen Kritchevsky, Ph.D., Wake Forest School of Medicine, and Anoop Nambiar, M.D., and Nicolas Musi, M.D., University of Texas.
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People living in socially-deprived areas of the United Statesare more likely to die prematurely from cardiovascular (CV) complications according to new research published recently in Mayo Clinic Proceedings.The study, completed by researchers at University Hospitals (UH) Harrington Heart & Vascular Institute, found social deprivation can explain a significant proportion of the geographic variation in premature cardiovascular mortality in the U.S.
Socioeconomic deprivation is defined by a number of social and economic factors including education, income, employment and neighborhood environment. A large gap exists in explaining premature CV deaths across the U.S. which cannot be totally attributed to traditional risk factors such as high cholesterol. Recent evidence suggests socioeconomic deprivation is a risk factor for this type of mortality.
“Socioeconomic status plays a big role in access to preventive care, risk factor control, and incidence of disease,” said Sadeer Al-Kindi, MD, cardiologist and co-director of the Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) with UH Harrington Heart & Vascular Institute and the study’s senior author. “UH is committed to improving the health of all people by advancing science and human health. A large part of that is discovering the root cause of disease. With this study, we wanted to determine whether premature cardiovascular mortality is associated with socioeconomic deprivation and how premature cardiovascular mortality changed over time by social deprivation.”
In “Socioeconomic Deprivation and Premature Cardiovascular Mortality in the United States” researchers completed a cross-sectional analysis of United States county-level death certificate data from 1999 to 2018 using files maintained by the U.S. National Center for Health and Statistics. They looked at people from the ages of 25 to 64 who died from cardiovascular conditions. They used linear regression analysis to document two integrated metrics of socioeconomic deprivation: Social Deprivation Index (SDI) and county Area Deprivation Index (ADI).
Results from this research showed that counties with high social deprivation had the highest rates of premature cardiovascular deaths. Additionally, from 1999 to 2018 premature cardiovascular mortality decreased to a lesser extent in socially deprived counties compared with affluent counties. In fact, indicators of social deprivation directly explained a significant proportion of the geographic differences in premature CV mortality in the U.S.
“Health and structural inequities in poor communities have been ignored for too long. We now know that where you live, inequities and other components embedded in the environment are powerful determinants of mortality, often from chronic non-communicable disease. Most importantly, shedding light on this pervasive issue compels us to act upon the information,” said Sanjay Rajagopalan, MD, Chief of Cardiovascular Medicine and Chief Academic and Scientific Officer of UH Harrington Heart & Vascular Institute and co-author of the study, as well as the Herman K. Hellerstein, MD, Chair in Cardiovascular Research.
UH is taking action in a multitude of ways, including through its work in the community thanks to the ACHIEVE GreatER initiative. A “transformative” $18.2 million federal grant from the National Institutes of Health’s P50 program will facilitate medical and cardiovascular care provided directly to people living in Cuyahoga Metropolitan Housing Authority, one of the nation’s largest and oldest subsidized housing programs. Additional efforts by the study team are focused on understanding the integrated social and environmental underpinnings of premature cardiovascular disease in Northeast Ohio and nationally.
“Regardless of where they live or how much money they make, all people should have the opportunity to receive the necessary medical resources and support to have a healthier life,” said Dr. Mehdi Shishehbor, DO, MPH, PhD, President of UH Harrington Heart & Vascular Institute, and the Angela and James Hambrick Chair in Innovation.
Prior studies have explored the relationship between race and premature CV mortality or individual socioeconomic factors (income, high school education) and CV mortality.
“To our knowledge, this is the first study to demonstrate a longitudinal association between multiple integrated metrics of socioeconomic deprivation and premature cardiovascular mortality adjusted for traditional cardiovascular risk factors, while also showing potentially worsening disparities,” said Dr. Al-Kindi.

University of Queensland researchers have demonstrated a genetic link between endometriosis and ovarian cancer subtypes enabling them to identify potential drug targets for therapy and increasing the understanding of both diseases.
Previous studies have shown that endometriosis sufferers have a slightly increased risk of developing epithelial ovarian cancer.
Dr Sally Mortlock and Professor Grant Montgomery from UQ’s Institute for Molecular Bioscience carried out a large genetic study to identify a genetic basis for this risk with a view to better understand the biological overlap between these reproductive disorders.
“More information about how they develop, their associated risk factors, and the pathways shared between endometriosis and different types of ovarian cancer has been needed,” Dr Mortlock said.
Endometriosis is a chronic debilitating disease that affects the health of 1 in 9 women of reproductive age, where tissue similar to the uterus lining grows in other parts of the body, causing pain and infertility.
“Our research shows that individuals carrying certain genetic markers that predispose them to having endometriosis also have a higher risk of certain epithelial ovarian cancer subtypes, namely clear cell and endometrioid ovarian cancer.”
Dr Mortlock said that although the diseases are genetically linked, the risk of ovarian cancer for those with endometriosis is not substantially increased.
“Overall, studies have estimated that 1 in 76 women are at risk of developing ovarian cancer in their lifetime and having endometriosis increases this slightly to 1 in 55, so the overall risk is still very low,” she said.
The study found genes that could be drug targets to treat both endometriosis and epithelial ovarian cancer in the future.
“We explored specific areas of DNA that increase the risk of both diseases and identified genes in ovary and uterus tissue that could be targets for therapy and may be valuable to understand the link between the disorders and to disrupt biological pathways initiating cancer.”
The researchers combined large datasets comparing the genomes of 15,000 people with endometriosis and 25,000 with ovarian cancer to find an overlap in risk factors between the two diseases.
The collaboration also involved Associate Professor Kate Lawrenson at Cedars-Sinai Medical Center and Dr Siddhartha P. Kar from the University of Bristol.
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Immune cells could help predict the prognosis of patients with the rare neurological disease amyotrophic lateral sclerosis (ALS), says a study published today in eLife.
The findings suggest that measuring changes in immune cell populations may help physicians monitor the status of patients with ALS. They also hint at a protective role that some immune cells might play in the disease, while others speed up disease progression. These new insights could help scientists find novel ways to treat ALS.
There are currently no effective treatments or cures for ALS, and the exact cause of the disease remains unclear. “Some studies implicate the immune system in ALS, but few have tracked immune cell populations in patients over time,” explains first author Can Cui, a PhD graduate at the Unit of Integrative Epidemiology, Karolinska Institutet, Stockholm, Sweden. “We set out to track immune changes in patients with ALS and determine if they could predict the patients’ prognosis.”
Cui and colleagues recruited 288 ALS patients living in Stockholm to participate in the study. They collected blood samples from the patients at the start of the study and at regular intervals afterward. They then tracked the relationship between immune cells in the samples and the participants’ disease progression for up to five years.
They found that the number of immune cells called leukocytes, neutrophils and monocytes increased in the participants during this period. As this happened, it became more difficult for the patients to complete basic physical tasks such as swallowing, holding utensils, or walking up and down stairs. However, there was no link between the levels of these cells in the body and a patient’s risk of death.
In a subsample of 92 patients — the ‘FlowC cohort’, in which 88% of participants were also included in the main cohort of 288 — the team measured 23 subpopulations of lymphocytes (a type of white blood cell) in the patients’ blood. They found that those with higher counts of natural killer cells and higher proportions of Th2-differentiated CD4+ T cells were likely to have better survival. However, higher proportions of CD8+ T cells and CD4+ EMRA T cells were associated with worse survival.
“Immune cells appear to play a dual role in ALS,” Cui explains. “Higher numbers of neutrophils and monocytes reflect worsening motor function in patients, while higher T-cell levels may be associated more clearly with survival.”
“These discoveries have important implications for understanding ALS and may contribute to the development of treatments that target specific immune cells,” adds co-author Caroline Ingre, Head of the ALS Center at Karolinska University Hospital, Solna, Sweden.
The authors add that there are a number of limitations to their study. For example, their analysis of cell types and proportions in the participants should be interpreted with caution, as not all patients were able to contribute repeated cell measurements due to high mortality rates in ALS.
Despite the limitations, the research paves the way for learning more about how ALS progresses and finding potential new ways for monitoring patients. “Our results also suggest the need for further studies on whether targeting specific immune cells could help improve patient outcomes,” Ingre concludes.
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Fusing human retinal cells with adult stem cells could be a potential therapeutic strategy to treat retinal damage and visual impairment, according to the findings of a new study published in the journal eBioMedicine. The hybrid cells act by awakening the regenerative potential of human retinal tissue, previously only thought to be the preserve of cold-blood vertebrates.
Cell fusion events — the combination of two different cells into one single entity — are known to be a possible mechanism contributing to tissue regeneration. Though rare in humans, the phenomenon has been consistently detected in the liver, brain, and gastrointestinal tract.
A team led by ICREA Research Professor Pia Cosma at the Centre for Genomic Regulation (CRG) in Barcelona and funded by Fundació “la Caixa” has now found that cell fusion events also take place in the human retina.
The researchers tested whether cell fusion events could differentiate into cells that turn into neurons, which would show potential for tissue regeneration. The team fused Müller glia, cells that play a secondary but important role in maintaining the structure and function of the retina, with adult stem cells derived from human adipose tissue or bone marrow.
“We were able to carry out cell fusion in vitro,creating hybrid cells. Importantly, the process was more efficient in the presence of a chemical signal transmitted from the retina in response to damage, resulting in rates of hybridisation increasing twofold. This gave us an important clue for the role of cell fusion in the retina,” says Sergi Bonilla, postdoctoral researcher at the CRG at the time of publication and first author of the study.
The hybrid cells were injected into a growing retinal organoid, a model that closely resembles the function of the human retina. The researchers found that the hybrid cells successfully engrafted into the tissue and differentiated into cells that closely resemble ganglion cells, a type of neuron essential for vision.
“Our findings are important because they show that the Müller Glia in the human retina have the potential to regenerate neurons,” says Pia Cosma. “Salamanders and fish can repair damage caused to the retina thanks to their Müller glia, which differentiate into neurons that rescue or replace damaged neurons. Mammalian Müller glia have lost this regenerative capacity, which means retinal damage or degradation can lead to visual impairment for life. Our findings bring us one step closer to recovering this ability.”
The authors caution that much work remains to be done before the development of any potential treatments. One of the next steps is understanding why hybrid cells — with four complete sets of chromosomes — don’t result in chromosomal instability and cancer development. The authors of the study believe the retina may have a mechanism regulating chromosome segregation similar to the liver, which contains tetraploid cells that act as a genetic reservoir, undergoing mitosis in response to stress and injury.
The study was led by the Centre for Genomic Regulation in collaboration with the Institute for Bioengineering of Catalonia (IBEC) and the Barraquer Ophthalmology Center. The work is mainly funded by the CaixaResearch Health Research Call from Fundació “la Caixa” awarded to Pia Cosma (CRG), Nuria Montserrat (IBEC) and Justin Christopher D’Antin (Barrraquer). It is also funded by the European Union’s FET-Open EcaBox project, Velux Stiftung, the Spanish Ministry of Science and Innovation and the Catalan Agency for Management of University and Research (AGAUR).
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The risk of suffering an ischaemic stroke, the most common type of cerebrovascular event, is 16% less in people who have green spaces less than 300 metres from their homes. This has been revealed in a joint study by the Hospital del Mar Medical Research Institute, Hospital del Mar, the Catalan Health Quality and Assessment Agency (AQuAS) from the Catalan Government’s Department of Health and the Barcelona Institute for Global Health (ISGlobal), a centre promoted by the “la Caixa” Foundation. It is the most important work in this field to date in Europe, analysing data on the entire population of Catalonia between 2016 and 2017. It has been published in the journal Environment International.
The study took into account information on exposure to three atmospheric pollutants linked to vehicle traffic in more than three and a half million people selected from among the 7.5 million residents of Catalonia, over the age of eighteen who had not suffered a stroke prior to the start of the study. Specifically, it analysed the impact of the levels of particulate matter under 2.5 microns (PM2.5), nitrogen dioxide (NO2) and soot particles at the place of residence of each of the people studied. The number and density of green spaces within a 300-metre radius of their homes was also studied. The data was obtained via geographic referencing and by designing models of exposure to the two determinants, using population data obtained by reusing health information generated in Catalonia and anonymised by the Data Analytics Programme for Research and Innovation in Health (Programa d’Analítica de Dades per a la Recerca i la Innovació en Salut; PADRIS) and managed by the Catalan Agency for Health Quality and Assessment (Agència de Qualitat i Avaluació Sanitàries de Catalunya; AQuAS).
More pollution, a higher risk of stroke
The results indicate a direct relationship between increased levels of NO2 in the atmosphere and the risk of ischaemic stroke. For every increase of 10 micrograms (µg) per cubic metre, this risk increases by 4%. The same happens when PM2.5 levels increase by 5 µg/m3. In the case of soot particles, the risk increases by 5% for every 1 µg/m3 increase in the atmosphere. These figures are the same for the entire population, irrespective of other socio-economic factors, age or smoking habits.
“It should be borne in mind that, unlike other air pollutants, which have various sources, NO2 is mainly caused by road traffic. Therefore, if we really want to reduce the multiple risks that this pollutant poses to people’s health, we need to implement bold measures to reduce car use”, says Cathryn Tonne, a researcher at ISGlobal.
“The study demonstrates the importance of environmental determinants in stroke risk. Given that it is predicted that the incidence, mortality and disability attributed to the disease will increase in the coming years, it is important to understand all the risk factors involved”, explains Dr. Carla Avellaneda, a researcher in the Neurovascular Research Group at IMIM-Hospital del Mar and one of the main authors of the study. Previous studies by the same group had already provided evidence on the relationship between factors such as soot or noise levels and the risk of suffering a stroke and its severity. All these factors act as stroke triggers.
In contrast, having an abundance of green spaces within the same radius from the home directly reduces the risk of suffering a stroke. Specifically, up to 16%. In this sense, “People who are surrounded by greater levels of greenery at their place of residence are protected against the onset of stroke”, says Dr. Avellaneda. Exposure to green spaces is generally considered to have beneficial effects through a variety of mechanisms, such as stress reduction, increased physical activity and social contact, and even exposure to an enriched microbiome.
Rethinking established air pollutant limits
In view of this data, the researchers point out that it is necessary to reflect on the current levels of atmospheric pollution that are considered safe. At the moment, the thresholds set by the European Union are 40 µg/m3 for NO2, which the World Health Organisation reduces to 10 µg/m3, and 25 µg/m3 for PM2.5, which the WHO limits to 5 µg/m3. Currently, no levels have been set for soot particles. In fact, the levels recorded during the period analysed were lower, on average, than those set by the European authorities (17 µg/m3 for PM2.5, 35 µg/m3 for NO2 and 2.28 µg/m3 in the case of soot).
“Despite compliance with the levels set by the European Union, we are faced with the paradox that there is still a health risk, such as the one we identified in this study, where there is a direct relationship between exposure to pollutants in our environment and the risk of suffering a stroke”, explains Dr. Rosa Maria Vivanco, lead author of the study and researcher at AQuAS and IMIM-Hospital del Mar. “The danger is still present and many more measures need to be taken”, considering the increase in the urban population and its ageing, she adds.
In this sense, Dr. Jaume Roquer, head of the Neurology Service at Hospital del Mar and coordinator of the Neurovascular Research Group at IMIM-Hospital del Mar, points out that “This study demonstrates the real impact that environmental aspects have on the health of the Catalan population. In view of the effects of atmospheric pollution, the lack of green spaces, noise, and so forth, more efforts and populational strategies are needed to reduce its impact. Its harmful effects are permanently and globally damaging. We must strive to achieve more sustainable towns and cities where living does not mean an increased risk of disease.”

The blood-brain barrier plays an essential role in protecting the central nervous system from harmful bacteria, toxins, and other blood-borne pathogens.
Composed of a tight row of endothelial cells, the barrier is semipermeable and highly selective. It allows small molecules and nutrients to pass from the blood into the central nervous system, while blocking substances that might cause infection, inflammation, and otherwise disrupt the system’s delicate balance.
However, what exactly controls the permeability of the blood-brain barrier is a question that has long bedeviled scientists — and one that Chenghua Gu, professor of neurobiology in the Blavatnik Institute at Harvard Medical School and a Howard Hughes Medical Institute investigator, has been studying for almost a decade.
Previously, Gu and her team at HMS established that a cellular trafficking system called transcytosis plays a key role in controlling blood-brain barrier permeability by determining how easily molecules can be transported across it. Now, new research in mice has revealed more details about how this process is regulated.
In this new research, published March 15 in Neuron, the scientists describe a mechanism by which cells in the surrounding environment, or microenvironment, signal to cells that make up the blood-brain barrier. They found that this intercellular communication inhibits transcytosis to keep the barrier less permeable and ensure that molecules cannot easily pass through.
“Our work opens the door to better understand how and why the microenvironment is important for maintaining the blood-brain barrier,” Gu said, which could inform the development of better laboratory models to study the blood-brain barrier.

The parasites that cause a disfiguring skin disease affecting about 12 million people globally may have met their match in vaccines developed using CRISPR gene-editing technology, new research suggests.
Phase 1 human trials are set to start later this year with a vaccine designed to prevent infection by Leishmania major, the parasite species that causes cutaneous leishmaniasis in tropical and subtropical regions of the Eastern Hemisphere.
The same research team, co-led by Abhay Satoskar, professor of pathology in The Ohio State University College of Medicine, has used CRISPR technology to develop a vaccine targeting Leishmania mexicana, the species of the parasite that is found in South, Central and North America.
In mice, the vaccine — created with a mutated live parasite — posed no threat of causing skin lesions and provided long-term infection prevention.
This “New World” species causes a more chronic infection that, unlike skin lesions generated by L. major infection, will not self-heal. Researchers expect the L. major mutant parasite vaccine to be effective against the L. mexicana species, but have developed the second vaccine as a backup — and to find out whether their technique could tame the more virulent organism.
“The main thing we wanted to see was if this approach, removing a specific gene, could break this tough cookie, which has always been a problem. It’s not an easy parasite,” said Satoskar, also a professor of microbiology at Ohio State. “Based on our experimental data, we should be able to use the L. major vaccine in the New World. But if it doesn’t work, we have a plan b.”
The study is published in the journal NPJ Vaccines.