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International research led by the Translational Synthetic Biology Laboratory of the Department of Medicine and Life Sciences (MELIS) at Pompeu Fabra University has succeeded in efficiently engineering Cutibacterium acnes -a type of skin bacterium- to produce and secrete a therapeutic molecule suitable for treating acne symptoms. The engineered bacterium has been validated in skin cell lines and its delivery has been validated in mice. This finding opens the door to broadening the way for engineering non-tractable bacteria to address skin alterations and other diseases using living therapeutics.
The research team is completed by scientists from the Bellvitge Biomedical Research Institute (Idibell), the University of Barcelona, the Protein Technologies Facility of the Centre for Genomic Regulation, Phenocell SAS, Medizinische Hochschule Brandenburg Theodor Fontane, Lund University, and Aarhus University.
Acne is a common skin condition caused by the blockage or inflammation of the pilosebaceous follicles. Its appearance can vary, ranging from whiteheads and blackheads to pustules and nodules, mainly on the face, forehead, chest, upper back and shoulders. Although acne is most common among adolescents, it can affect people of all ages.
The most severe cases of acne are treated with antibiotics to kill bacteria living in the follicles, or isotretinoin (known as Accutane), a vitamin A derivative, which induces the death of sebocytes, the epithelial skin cells that produce sebum. However, these treatments can cause serious side effects such as breaking skin microbiome homeostasis -because they are not selectively killing bacteria- or photosensitivity, in the case of antibiotics, or birth defects or extreme scaling of skin, in the case of isotretinoin.
The results of the study, published today in Nature Biotechnology, show that researchers have successfully edited the genome of Cutibacterium acnes to secrete and produce NGAL protein known to be a mediator of the acne drug, isotretinoin, that has been shown to reduce sebum by inducing the death of sebocytes.
“We have developed a topical therapy with a targeted approach, using what nature already has. We engineered a bacterium that lives in the skin and make it produce what our skin needs. Here, we focused on treating acne, but this platform can be extended to several other indications,” says Nastassia Knödlseder, first author of the study.
Broadening the way of engineering bacteria
“Until now, C. acnes was considered an intractable bacterium. It was incredibly difficult to introduce DNA and get proteins produced or secreted from an element inserted into its genome,” explains Knödlseder, who is a postdoc in the UPF Translational Synthetic Biology Laboratory.

However, since C. acnes seems an attractive synthetic biology chassis for treating skin diseases due to its niche environment deep inside hair follicles -practically where sebum is released-, its importance for skin homeostasis, its close contact to relevant therapeutic targets, plus the fact that it has been shown to successfully engraft when applied to human skin, led them to insist on editing the genome of this non-engineerable bacterium.
To edit the genome of C. acnes, the research team led by Marc Güell has focused on improving DNA delivery to the cell, DNA stability inside the cell, and gene expression. The scientists have considered regulatory measures by developing a biocontainment strategy to avoid the use of elements that generate regulatory concerns such as mobile genetic elements, plasmids or antibiotic resistance. Hence, the resulting synthetic bacterium has safety features to enable “real-life application” and consider it for future human therapeutics.
Synthetic C. acnes is able to secrete and produce NGAL to modulate sebum production in cell lines. When applied to the skin of mice -the only animal model able to test engineered bacteria to date- they engraft, live and produce the protein. However, mice skin it is not comparable to humans’. It has more hair, is looser, has less lipids and a different sweat mechanism. Hence the need for an alternative model, better representing human skin, such as 3D skin models.
The road to therapeutics
“We have developed a technology platform that opens the door to editing any bacteria to treat multiple diseases. We are now focused in using C. acnes to treat acne but we can deliver genetic circuits to create smart microbes for applications related to skin sensing, or immune modulation,” points out Marc Güell, who has led the research.
Following the same strategy, this research line will continue under the European Project ‘SkinDev’ in which scientists from the Translational Synthetic Biology lab together with its partners will engineer C. acnes to address atopic dermatitis, a chronic cutaneous inflammatory condition characterized by dry skin, eczema and severe irritation, especially common among young children.
Although any living therapeutics strategy should be validated individually, the researchers show their optimism in applying these smart microbes to humans because non-engineered C. acnes has already been tested on the skin of patients safely and effectively.

Brown fat cells convert energy into heat — a key to eliminating unwanted fat deposits. In addition, they also protect against cardiovascular diseases. Researchers from the University Hospital Bonn (UKB) and the Transdisciplinary Research Area “Life & Health” at the University of Bonn have now identified the protein EPAC1 as a new pharmacological target to increase brown fat mass and activity. The long-term aim is to find medicines that support weight loss. The results of the study have now been published in the journal Nature Cell Biology.
Obesity is defined as a pathological increase in white fat, and has become a major problem worldwide, with a greatly increased risk of cardiovascular diseases such as heart attack and stroke. “Exercise and dieting are not enough to effectively and permanently shed the pounds,” says corresponding author Prof. Alexander Pfeifer, Director of the Institute of Pharmacology and Toxicology at the University Hospital Bonn and member of the Transdisciplinary Research Areas (TRA) “Life & Health” and “Sustainable Futures” at the University of Bonn. “Our energy-dense foods lead to energy being stored in white fat. But losing weight isn´t that easy, as the body saves energy in response to a low-calorie diet. So our goal is to achieve additional energy release.”
Aim are therapies that keep the energy balance in equilibrium
Brown fat cells, on the other hand, act as a biological oven and ensure, for example, that newborn babies can cope with cold exposure after birth. However, adults hardly have any brown fat, and it can be found mainly in young and slim people. “We therefore asked how brown fat mass can be increased while simultaneously reducing bad white fat,” says Bonn postdoctoral researcher and first author Dr. Laia Reverte-Salisa.
Together with researchers from the University Medical Center Hamburg-Eppendorf, Helmholtz Munich and the University of Toulouse-Paul Sabatier, the Bonn team investigated the cAMP signaling pathway in fat metabolism that plays a central role in fat cells. Using a mouse model, they discovered that the relatively unknown protein “exchange proteins directly activated by cAMP” (EPAC1), is responsible for the growth of brown fat. In addition, EPAC1 even increases the formation of brown fat cells in white fat, which are also known as “beige” cells. Prof. Pfeifer’s team also showed that the signaling pathway is also active in human fat cells. In addition, they confirmed the function of EPAC1 in human organoids — organ-like microstructures that serve as a human brown fat model.
The Bonn researchers further found that a non-functional human EPAC1 gene variant is associated with an increased body mass index (BMI). “Our study shows that EPAC1 is an attractive target to increase brown fat mass and thus also energy expenditure,” says Prof. Pfeifer. In view of the worldwide increase in obesity, he hopes to develop novel therapies that help those affected to combat metabolic diseases. This study was conducted in the context of the DFG Collaborative Research Center Transregio-SFB 333 “Brown and Beige Fat — Organ Interactions, Signaling Pathways and Energy Balance (BATenergy),” which is pursuing a better understanding of the different types of adipose tissue and their role in metabolic diseases.

Decisions on treatment for patients with acute myeloid leukemia (AML) — a highly aggressive form of leukemia — are based, among other things, on a series of certain genetic features of the disease; but at the time when a diagnosis is made, this information is not available. However, evidence of these genetic anomalies is crucial in providing targeted treatment for patients at an early stage. As genetic testing is expensive and time-consuming, there is a great need for inexpensive, fast and broadly accessible tests to predict such anomalies.
A team of IT specialists and physicians at the University of Münster and the University Hospital Münster has now published a study showing how a method based on artificial intelligence (AI) can be used to predict various genetic features on the basis of high-resolution microscopic images of bone marrow smears. As a result, decisions on a more precise treatment can be made in future directly on the day of the diagnosis, without the need to wait for genetic analyses. The results have been published in the journal Blood Advances.
In this new method, the genetic aberrations were extracted directly from extremely high-resolution multi-gigabyte scans from whole bone marrow smears taken from more than 400 AML patients. The scans had a resolution of 270,000 times 135,000 pixels on average, with one image being several gigabytes in size. Proceeding from this enormous dataset, it was possible to extract more than two million single-cell images. “We developed a new type of Deep Learning method, fully automatic, which was trained for a complex task by means of machine learning technology,” explains Prof. Benjamin Risse, who headed the work on algorithmic developments on the IT side. “In our case, the basic algorithm can automatically recognise the genetic features and the very fine patterns in big cytological images. The method then filtered the single-cell images into categories of different cell types, and it also showed any genetic aberrations. Interestingly, several patterns recognized by the algorithm can not be identified by human observers. This is for example because the patterns may be too faint or because extremely fine textures are involved which remain hidden to the human eye, despite excellent imaging,” says Risse.
One key advantage of the method presented is in the end-to-end AI pipeline which enables monitoring of the (interim) results and reduces to a minimum the manual preliminary work often necessary for machine learning. This is made possible by a combination of so-called unsupervised, self-supervised and supervised learning processes. The first two processes require no manual data selection at all but try to extract relevant content automatically from the image data instead. “Using a so-called incremental approach, we carried out intermediary steps with a human expert to examine the images. This is necessary for example in cell images categorised as problematic,” says Dr. Linus Angenendt, who heads the Personalised Cancer Therapy and Digital Medicine working group at Münster University Hospital. Problematic cell images can occur as a result of incorrect staining, for example. The model trained was subsequently evaluated on an independent dataset relating to a further 70 patients with over 440,000 single-cell images — as a test cohort.
Although the new method cannot replace genetic analyses, it nevertheless helps at a very early stage in the diagnostic clarification process for a leukaemia patient, by providing an idea of which genetic aberrations might underlie the disease. This would be especially helpful in the case of aggressive diseases when there is no time to wait for the complete genetic analyses.
The researchers are confident that in future digital methods and artificial intelligence will become increasingly important for large medical datasets when it is a question of making personalised recommendations for treatment for patients with malignant diseases. This study contributes an important basis for this, for example in the development of similar approaches for other bone marrow diseases.

Endocrine resistance — a major cause of breast cancer deaths — can be underpinned by an epigenetic change called DNA methylation, researchers at the Garvan Institute of Medical Research have discovered. The team successfully reversed this methylation to reduce cancer growth in patient-derived animal models.
Using a low dose of the epigenetic therapy drug decitabine, which is currently used to treat some blood cancers, the researchers significantly suppressed the growth of endocrine-resistant breast tumours in mice and increased survival time by 90%. The finding, which will be tested in a future Phase I clinical trial, is a potential gamechanger for the more than 4,000 people who are diagnosed with endocrine-resistant breast cancer each year in Australia alone.
“This research has uncovered a completely new approach to treating endocrine-resistant breast cancer. In our study, we have not only pinpointed a new molecular mechanism that explains how endocrine resistance might develop — we have identified a treatment currently used in the clinic that can target this mechanism precisely,” says Professor Susan Clark, Head of the Cancer Epigenetics Laboratory at Garvan and senior author of the paper published in Nature Structural & Molecular Biology.
Epigenetic change drives breast cancer treatment resistance
An estimated 70% of all diagnosed breast cancers are oestrogen receptor positive (ER+), which means their growth is activated by oestrogen — a hormone that plays a key role in sexual and reproductive health in women. While endocrine therapy that suppresses oestrogen in the body can slow or stop the growth of these tumours, more than 30% of patients develop resistance, with their tumours no longer requiring oestrogen to grow.
In a 2020 study, the Garvan team investigated the endocrine-resistant cancer’s epigenome, the layer of instructions that organises and regulates DNA’s activity, and revealed that endocrine resistance is linked to methyl groups attaching to regulatory regions of DNA and changing the 3D structure of DNA inside cancer cells.
New approach to breast cancer therapy
“In this current study, we set out to reverse the abnormal methylation patterns and restore the 3D DNA structure in the endocrine-resistant ER+ breast cancers using epigenetic therapy,” says first author Dr Joanna Achinger-Kawecka, Head of the 3D Epigenome in Cancer Group at Garvan. “We found that decitabine removed methyl groups at specific DNA regulatory regions, rewiring the 3D structure of DNA to not only reactivate the production of oestrogen receptors, but also activate tumour suppressor genes that can reduce cancer growth.”

“After treating patient-derived endocrine resistant breast cancer tumours with decitabine alone, we were surprised to see cancer growth significantly reduced in mice,” says co-first author Associate Professor Clare Stirzaker, Head of the Epigenetic Biomarker Group. “This highlights the importance of studying fundamental molecular mechanisms to best guide targeted treatments.”
Decitabine is an FDA- and TGA-approved epigenetic therapy currently used to successfully treat certain blood cell cancers, including myelodysplastic syndromes, but there are limited studies in other cancers. While the current study focused on ER+ breast cancer, the researchers say the drug may also have potential for other endocrine-resistant cancers driven by epigenetic changes.
“The next stage of our research will be to test decitabine together with endocrine therapy, which could be even more effectively target this difficult-to-treat cancer,” says Professor Clark. “We hope that such a combination approach is a turning point that enables significantly better clinical outcomes.”
This research was supported by Australia’s National Health and Medical Research Council (Project Grant #1128916), the National Breast Cancer Foundation (IIRS-21-047), Cancer Council NSW (RG20-04 and RG16-02) and the Van Andel Institute Stand Up To Cancer Epigenetics Dream Team.
Professor Susan Clark is a Conjoint Professor, Dr Joanna Achinger-Kawecka is a Conjoint Lecturer and Associate Professor Clare Stirzaker is a Conjoint Associate Professor at St Vincent’s Clinical School, Faculty of Medicine and Health, UNSW Sydney.

It may sound strange, but we can actually learn more about ourselves by studying pigs.
Pigs and humans are pretty similar. Our organs, our skin and the way many diseases develop are largely the same.
Pigs have therefore long been used to develop and test new medicines, even though pigs are larger, more expensive and more difficult to use in experiments than rats and mice.
And now pigs may become even more valuable as laboratory animals, because researchers from the Center for Quantitative Genetics and Genomics at Aarhus University have mapped the most important genetic similarities between pigs and humans.
The researchers have not only identified the genes that are the same in humans and pigs; they have also identified the so-called ‘transcriptome’ across a number of tissue types. Where the genome includes all the genes found in the DNA of our cells, whether active or inactive, the transcriptome includes the genes that are active in the different types of cells in our body, says Lingzhao Fang, one of the main researchers behind the new findings.
“We examined which genes are active and how they are regulated in 34 different types of tissue in pigs, and compared this with similar studies in humans. We looked at everything from testicular tissue to skin cells and various brain cells,” he says and continues:
“No one has ever conducted a study at this scale and comprehensiveness, and we hope the new knowledge can make a difference in agriculture as well as in the pharmaceutical industry.”
More useful knowledge from RNA

A little more than 20 years ago, a group of more than 1,000 researchers succeeded in mapping the entire human genome. After completing the project, the researchers hoped they could now develop treatments for nearly all diseases, because they now knew the code and could identify the errors.
But that is not how the story went.
The researchers soon discovered that there is a big difference between the genes in an individual’s recipe book and the recipes that are actually used and translated in the various cell types.
This is what is also referred to as genotype and phenotype, with phenotype referring to the traits or symptoms that can be observed in an individual. Because of the greater role played by the transcriptome, a person can have the genetic disposition for a disease without actually suffering from the disease.
In other words, two people who, on paper, have the same disease mutation do not necessarily become ill to the same extent. With greater knowledge about the role of the transcriptome in various diseases, it is possible to develop better and more targeted medicines.
And this is one area in which the results from Lingzhao Fang’s study can be useful when it comes to pigs as laboratory animals.

“Pigs become more suited as animals for testing new medicines. As the various tissue types in pigs and humans are very similar, in fact more similar than we thought, the pharmaceutical industry can test the safety of new medicines in pigs with much higher accuracy,” he says.
Can also help agriculture become greener
The pharmaceutical industry is not the only industry to potentially benefit from the new results. Agriculture can also use the results in their efforts to breed pigs with a reduced climate impact, according to Lingzhao Fang.
“There’s never before been such a comprehensive mapping of the genes that are active in various tissue types. Our results make it possible to more precisely pinpoint the genetic mechanisms that lead to different desirable traits in pigs,” he says and continues:
“For example, traits that make them more climate-friendly. Our mapping also paves the way for researchers to edit pig genes far more precisely and in this way develop entirely new properties in the future. Because we now know more about a wide range of traits in pigs, other researchers can more easily use gene-editing techniques such as CRISPR to change genes or insert new sequences with greener properties.”
Mapping other animals as well
Pigs are actually not the first animal whose transcriptome Lingzhao Fang and his colleagues have mapped. They started with cows a few years ago, and they plan to map a number of other animals in the coming years.
“We already have a study on chickens in the pipeline. It’s currently being peer-reviewed, but we hope to publish it early next year,” he says.
In addition to chickens, pigs and cows, the research team is studying goats, sheep, horses and ducks using the same method. He explains that the ultimate objective is not only to make agriculture greener but also to obtain a better understanding of fundamental animal and human biology.
“Once we’ve completed the project, we’ll have gained a greater basic understanding of the biology and evolution of a number of animals. This knowledge can be useful in other areas,” he says and continues:
“For example, we have problems with disease transmission between humans and farm animals. Our mapping may provide us with the necessary knowledge to limit and prevent outbreaks in the future.
One of the reasons why Lingzhao Fang is studying farm animals and not wild animals is that it is easy to access tissue samples and large amounts of data. However, the knowledge obtained can also be used in relation to wild and even extinct animals.
“We will gain a fundamental understanding of the biology of several different animals, and these all have wild cousins who basically function in the same way,” he concludes.
DNA, RNA and transcriptomes
In the centre of every human and pig cell, inside a small nucleus, are the long, two-stranded DNA molecules that make up the chromosomes. The strands consist of almost endless rows of four small molecules that we abbreviate to A, C, G and T.
The sequence of the four molecules is what forms our genes. A gene is a sequence of the four molecules and it serves as a recipe for a protein.
However, before the cell can produce one of the many different proteins for which it has recipes in its DNA, the sequence must be translated. This happens when the two strands of DNA unwind where the recipe is located and a so-called RNA strand binds to this place and copies the part of the code that makes up the gene. In simple terms, RNA is single-stranded DNA.
RNA leaves the cell nucleus and transports the code to the cell’s protein factories, the ribosomes, where the code is then translated into a protein.
All cells in our body have the same DNA, but the parts of the DNA code that are translated and activated differ from cell to cell. Liver cells have other active genes than skin cells, for example. Not all RNA sequences transport code to the protein factories. Instead, some bits attach themselves to other RNA sequences to stop them from being translated into proteins, or to ensure that the body produces even more of the protein in question.
The RNA sequences that are active in a specific type of cell are called the transcriptome. This is what the researchers have been studying in this research project.

Researchers from Binghamton University, State University of New York are unraveling the workings of Group B Strep (GBS) infections in pregnant women, which could someday lead to a vaccine.
One in five pregnant women carry Streptococcus agalactiae (Group B Strep or GBS) in the vaginal tract, which is typically harmless — except when it isn’t.
The bacterial infection poses serious and even fatal consequences for newborns, including pneumonia, sepsis and meningitis, which can have long-term effects on the child’s cognitive function.
Researchers from Binghamton University’s Biofilm Research Center and the School of Pharmacy and Pharmaceutical Sciences (SOPPS) are unraveling the workings of GBS infections, which could someday lead to a vaccine. Their article, “In silico and experimental analysis of the repeated domains in BvaP, a protein important for GBS vaginal colonization,” was recently published in Infection and Immunity.
“This research has identified and characterized a novel protein that could serve as a vaccine candidate to fight a bacterium that impacts women’s reproductive health and neonatal outcomes,” said first author Lamar Thomas PhD ’23, now a postdoctoral fellow at the University of California, San Diego, in the Department of Pediatrics. “I hope this work will inspire others to explore other novel proteins and microbial agents that may potentially aid in improving global health.”
When most people think of “strep,” they have in mind Streptococcus pyogenes — Group A Strep or GAS, which causes strep throat and necrotizing fasciitis, a “flesh-eating” infection, explained Assistant Professor of Biological Sciences Laura Cook, a co-author of the paper along with Nicholas Faiola of the Biofilm Research Center and Emily Canessa and Yetrib Hathout of SOPPS.
“There are many other pathogenic species of Streptococcus as well, including GBS and Streptococcus pneumoniae, which also causes many diseases, especially in the elderly,” she said.

GBS can pass from mother to child in utero, potentially causing preterm birth, or after birth via close contact like breastfeeding, but these infections are rare. Most commonly, the infection is transmitted from mother to child during the birthing process, likely due to the aspiration of contaminated bodily fluids. Because of the risks, pregnant women in the United States are tested during their last trimester and treated with antibiotics if they are found to be positive. While antibiotics have decreased the rates of neonatal GBS disease in developed countries, the World Health Organization has placed a high priority on developing a vaccine.
To successfully colonize, the bacteria create a biofilm that allows them to stick to each other and the human host. Key to that biofilm is a protein known as BvaP, which Cook’s lab established in previously published research.
Blocking surface proteins such as BvaP could be key to developing a successful vaccine, protecting newborns from infection. Cook’s lab is now looking at the regulation of this protein, how this affects its function and how it may interact with other GBS proteins and the host.
“Even if BvaP does not prove to be a viable vaccine candidate, the process of host colonization is essential to understand for developing treatment strategies against bacterial pathogens,” Cook said.

From a wartime spread of antimicrobial resistant disease in Ukraine, to superbugs in China causing “white lung” pneumonia in children, 2023 brought no shortage of new evidence that antimicrobial resistance (AMR) continues to be a pressing problem globally, and this pattern shows no sign of abating in 2024 unless a radical shift occurs.
To truly tackle the issue of AMR, York University researchers with the Global Strategy Lab (GSL) argue it needs to be understood as a socio-ecological challenge that accepts AMR as a phenomenon stemming from natural evolutionary processes. In other words, the war on bugs can’t be won; what’s needed is a major change in how people live with it.
“For the past hundred years, we’ve tried to address AMR like a medical problem. But we haven’t really made much progress in actually mitigating the deeper drivers of the issue,” says Isaac Weldon, a recent York PhD political science graduate and lead author of a new peer-reviewed article published today in the journal Perspectives on Politics journal. “We argue that there’s a lot of potential to make progress by instead looking at it as a problem with our relationship with the microbial world and sustainability.”
AMR stems from both the natural tendency of bacteria, viruses and fungi to evolve as well as the acceleration of that process through human interventions such as an over-reliance or misuse of antibiotics in medical settings, to the routine use of antimicrobials in the livestock industry. Global data from 2019 showed more than a million deaths a year directly related to AMR, and the COVID-19 pandemic seems to have accelerated this process.
Last year, GSL set up the AMR Policy Accelerator with $8.7 million from Wellcome Trust to deal with this urgent threat. While Weldon acknowledges that medical and technological innovation will be a crucial component in managing the issue, new antimicrobial drugs alone will not be the solution.
“What we’re currently doing is treating the symptoms and not the causes of AMR,” says Weldon, also an investigator with GSL. “Without addressing the underlying social relationships that drive our use, innovation would have to operate at an unsustainable speed as these microbes evolve faster than we can make new drugs.”
Weldon and co-author Steven J. Hoffman, director of GSL and Dahdaleh Distinguished Chair in Global Governance & Legal Epidemiology with York’s Faculty of Health and Osgoode Hall Law School, outline major problems with the current governance approach to AMR. They introduce five principles for designing institutions for a better ecological fit of human-microbial ecosystems to minimize drug resistance: There’s no silver bullet. Recognizing that there is no easy fit or one-fits all solution for AMR means problem-solving must always be tailored to specific ecological situations and health challenges of diverse populations. Create institutions that can adapt over time. Future proofing doesn’t mean creating institutions that are strong enough to withstand change, but ones flexible enough to evolve with the changing nature of AMR and our relationship to it. Diversify practices. As the best way to tackle AMR is still unknown, diversifying practices can help us discover what works, when, and where. Create records. As practices are diversified, records need to be kept of what works to enable learning and adjustments in policy. Involve stakeholders. This involves everyone from the public at large, to government and decision makers.”What we are proposing is a completely different way of looking at the issue,” says Hoffman. “We are hoping this journal article will be a foundational piece that will inspire further AMR research in this direction.”

Chronic exposure to arsenic, often through contaminated groundwater, has been associated with Type 2 diabetes in humans, and there are new clues that males may be more susceptible to the disease when exposed.
A new Cornell University study — using lab mice genetically modified with a human gene to shed light on the potential link — revealed that while the male mice exposed to arsenic in drinking water developed diabetes, the female mice did not.
These results would not have been possible without using a mouse model engineered to express a human enzyme for metabolizing arsenic, since normal mice process arsenic much more efficiently than humans and require very high levels of exposure before they become diabetic.
“Our paper lays the foundation for future investigations into the mechanism of how arsenic exposure leads to diabetes, why there are striking male-female differences, and potential therapeutic strategies,” said Praveen Sethupathy, professor of physiological genomics and the study’s senior author.
Endemic levels of arsenic above safe limits in both Bangladesh and Mexico led to studies that showed an association between higher levels of arsenic exposure and Type 2 diabetes. Though these studies had very small sample sizes, they offered clues for further research.
Mice in the study were exposed for a month to doses of arsenic in drinking water that were nonlethal but sufficient to potentially promote Type 2 diabetes. The researchers then examined liver and white adipose tissues that are implicated in diabetes. In the humanized male mice alone, they found increased expression in genes related to insulin resistance. Also, in both liver and white adipose tissues of the humanized male mice, they identified a biomarker called miR-34a, which is highly associated with insulin resistance in Type 2 diabetes and other metabolic diseases.
“This would suggest miR-34a is potentially a way to screen individuals who live in areas that have endemic arsenic levels,” said Jenna Todero, first author of the study and doctoral student in Sethupathy’s lab. “If you have elevated miRNA-34a, you might be at risk for Type 2 diabetes onset or other metabolic dysfunction.”
The study was funded by the Superfund Research Program at the National Institute of Environmental Health Sciences.

Leukemia is a common term used to refer to a form of blood cancer. However, there are different types of leukemia depending on the cell type involved. One unique form is myeloid/natural killer (NK) cell precursor acute leukemia (MNKPL). Because of its rarity, there is no consensus on the specific characteristics needed to clinically identify this disease. In a recent article published in Science Advances, a team led by researchers at Tokyo Medical and Dental University (TMDU) used various approaches to better assess the molecular profile and drug sensitivity characteristics of MNKPL.
MNKPL was only first proposed as a leukemia subtype in 1997. Extramedullary involvement is one of the hallmarks of MNKPL. It is prevalent in East Asian countries. Although the immunological phenotype of MNKPL was explored previously, a full genetic characterization of this cancer type had not been performed. These details would help support more accurate diagnoses for patients, which would lead to more appropriate therapeutic decisions. Therefore, the TMDU group aimed to investigate MNKPL on a single-cell level.
“A single-cell exploration of MNKPL would not only help us better understand its clinical and genomic features, but also clarify the specific cellular origin of this disease,” says Dr. Akira Nishimura, lead author of the study.
The team first used what is known as a multiomics approach to investigate MNKPL patient samples. They used various sequencing technologies to determine if there were any relevant mutations in specific genes, look for expression differences in certain signaling pathways at the RNA level, and examine any unique DNA methylation patterns.
“Our results demonstrate that MNKPL has molecular qualities that are distinct from other similar cancers, such as acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia,” explains Dr. Masatoshi Takagi, senior author. “Specific hallmarks of MNKPL include activation of the NOTCH1 and RUNX3, as well as lower expression of the BCL11B.”
Further work at the single-cell level in MNKPL cells showed that NK cells and myeloid cells come from a common progenitor cell type.
The researchers also conducted in vitro drug sensitivity assays where they measured MNKPL cell responses to 79 individual anti-cancer drugs.
“We observed that MNKPL cells were highly sensitive to a drug called L-asparaginase, which has already shown clinical effectiveness for this disease,” says Dr. Nishimura. “Mechanistically, we found that this was from low expression of asparagine synthetase, a quality that was distinct from other similar types of leukemia.”
Overall, the robust and comprehensive analysis performed in this study provides crucial molecular details for characterizing MNKPL. This work will undoubtedly help clinicians more effectively diagnose MNKPL and choice of therapeutic option. Additionally, this work provides data that will assist with novel therapeutic target identification and drug development in this leukemia.

In early 2020, the Food and Drug Administration responded to decades of escalating concerns about a commonly prescribed drug for asthma and allergies by deploying one of its most potent tools: a stark warning on the drug’s label that it could cause aggression, agitation and even suicidal thoughts.The agency’s label, which was primarily aimed at doctors, was supposed to sound an alert about the 25-year-old medication, Singulair, also known by its generic name, montelukast. But it barely dented use: The drug was still prescribed to 12 million people in the United States in 2022.Children face the greatest risks of the drug’s ill effects, and while usage by minors did decline, it was still taken by 1.6 million of them — including Nicole Sims’s son. Ms. Sims had no idea why, at 6, her son started having nightmares and hallucinations of a woman in the window. When he told her that he wanted to die, Ms. Sims went online, desperate for answers.Only then did she learn about the F.D.A. warning. She also found a Facebook support group with 20,000 members for people who had experienced side effects of the drug. Members of the group recounted a haunting toll that they linked to the drug with the help of peers, not their doctors.Singulair’s Boxed WarningThe Food and Drug Administration added a boxed warning to Singulair in 2020.