Publisher Health

Researchers have characterised the seasonal effects on human social behaviour to provide new insights on the risk of respiratory disease transmission.
Their large-scale analysis, published today in eLife, provides a framework of seasonal behaviour across the US that could be used in the construction of more evidence-based models of disease transmission.
The impact of the time of year on disease transmission is a familiar and widespread phenomenon, but the processes that cause this seasonality in transmission rates are still largely unclear.
“Models of infectious disease transmission have traditionally used environmental data-driven approaches. However, the seasonality of influenza, COVID-19 and other respiratory pathogens depends on people’s social behaviour as well as the environment,” explains first author Zachary Susswein, who was a Research Associate at senior author Shweta Bansal’s lab, Georgetown University, Washington, DC, US, at the time the study was carried out, and is now a Data Analyst at the Rockefeller Foundation, Washington, DC. “A key gap in understanding the role that social behaviour plays in respiratory disease seasonality is our incomplete knowledge of how the time of year impacts indoor mixing among people.”
To address this gap, the team used novel data on human mobility to characterise activity in indoor versus outdoor environments in the US. The data was taken from the SafeGraph Weekly Patterns dataset, which provides information on foot traffic at public locations, or ‘points of interest’ (POIs), across the US based on the usage of mobile apps with GPS. The data range from 2018-2020 and cover more than five million locations nationally. For their study, the team used 4.6 million POIs from the dataset over those three years.
From this data, they classified the locations that people visited as primarily ‘indoor’ (for example, stores and offices) or ‘outdoor’ (such as playgrounds and farmers’ markets). They then disentangled location-specific visits into indoor and outdoor to construct a novel metric that measures the tendency of people to mix indoors on a weekly scale. They found that the proportion of indoor to outdoor activity during a baseline year (2018 or 2019) is seasonal, peaking in the winter months. The measure shows stronger seasonality of indoor mixing at northern regions and an additional summer peak in southern regions.
Next, the team characterised the shift that occurred in these baseline patterns of seasonal indoor activity during the COVID-19 pandemic. To do this, they compared the mobility patterns they identified in 2018 and 2019 with those during the pandemic in 2020. They found that the pandemic disrupted the patterns identified in the baseline years: in early 2020, when there were substantial social distancing measures across the US (including remote work and school closures), activity was more likely to be outdoors than in previous years. In four case-study locations — Maricopa County, Arizona; Baltimore County, Maryland; Travis County, Texas; and Charleston County, South Carolina — most saw a shift in their indoor activity patterns from 2018 and 2019, while others (such as Maricopa County) did not. The authors say that the patterns identified in their analysis are necessary for predicting how the dynamics of different diseases might differ across locations and time of year, and how different communities may respond to behavioural interventions.
“Our results suggest that such public health strategies should be implemented in a targeted manner, informed by real-time data and with clear communication of the goals,” says author Eva Rest, who was a Master’s Degree student and Global Health Institute fellow at the Bansal Lab, Georgetown University, at the time the study was carried out, and is now an M.D.-Ph.D. student at the Yale School of Medicine, New Haven, Connecticut, US.
The authors acknowledge that while novel data streams offer opportunities to address long-unanswered questions, these data must be interpreted carefully. The SafeGraph data, although significant in its size, does not represent the activities of children under 16 years of age due to privacy laws, and may be less representative for elderly individuals due to lower smartphone usage.
“Additionally, our novel metric of indoor mixing may average across the experience of all groups, particularly by socioeconomic status,” explains senior author Shweta Bansal, Provost’s Distinguished Associate Professor at Georgetown University. Previous research has shown that low-income and racially marginalised communities can have systematically less access to outdoor, natural spaces and can spend more time indoors due to structural inequities such as lack of paid leave. “So, we may very well be underestimating the risk of infection experienced by individuals in these vulnerable communities, and we commit to continued work to better characterise this.”
Bansal concludes: “Our current work helps to improve our understanding of the relationship between the indoor environment and infection risk in the context of global change. While the COVID-19 pandemic and climate change may impact indoor activity in different ways, a greater understanding of the seasonality of indoor activity would allow policymakers and emergency preparedness experts to effectively address future disruptions.”

Researchers have long known that many animals live longer in colder climates than in warmer climates. New research in C. elegans nematode worms suggests that this phenomenon is tied to a protein found in the nervous system that controls the expression of collagens, the primary building block of skin, bone and connective tissue in many animals.
Since the C. elegans’ protein is similar to nervous system receptor proteins found in other species including humans, the discovery potentially brings scientists closer to finding ways to harness collagen expression to slow down human aging and increase lifespan in the midst of global warming. Led by scientists at Washington State University, the study was published in the journal Aging Cell.
“Based on animal studies, scientists anticipate that human lifespan will go down in the future as climate change drives up the ambient temperature,” said senior author Yiyong (Ben) Liu, an assistant professor in the WSU Elson S. Floyd College of Medicine and director of the university’s Genomics Service Center. “We have found that warm temperatures leading to short lifespan is not a passive, thermodynamic process as previously thought, but a regulated process controlled by the nervous system. Our findings mean that down the road, it may be possible to intervene in that process to extend human lifespan as temperatures rise.”
The researchers looked at a nervous system protein known as NPR-8 in the tiny soil-dwelling worm Caenorhabditis elegans (C. elegans), a commonly used model organism in aging research. During their study, they observed that worms lacking NPR-8 had fewer skin wrinkles as they aged. They also made the unexpected discovery that mutant worms kept at a warm temperature of 25 C (77 F) had increased collagen expression and lived longer than wild-type worms, which did not happen when the worms were kept at 20 C or 15 C (68 F and 59 F, respectively). To determine whether the neural regulation of collagens may play a role in aging and longevity, they conducted a series of additional experiments and analyses.
“What we saw was that the absence of NPR-8 caused an increase in collagen expression, which increased the worms’ stress resistance and lifespan and made them look younger than wild-type worms that were the same biological age,” said co-first author Durai Sellegounder, a former postdoctoral research associate in the WSU Elson S. Floyd College of Medicine who is now a scientist at the Buck Institute for Research on Aging.
In one experiment, the researchers reintroduced NPR-8 in mutant worms kept at 25 C and saw that this reverted the worms’ skin from smooth to wrinkled and significantly reduced the animals’ extended lifespan. Next, they showed that the extended lifespan of npr-8 mutant worms also held up under heat stress conditions, with mutant worms surviving significantly longer than wild-type worms when moved into a 35 C (95 F) environment. Additional experiments identified specific neurons responsible for regulating lifespan in response to warm temperatures and pointed to increased expression of collagens as a driver of the improved lifespan at warm temperatures.
The phenomenon of heat shortening lifespan has traditionally been explained by the rate of living theory, which suggests that heat speeds up an organism’s metabolism, causing it to use up its finite store of metabolic energy more quickly. While the researchers still found limited evidence supporting this idea, their study findings indicate that the nervous system also plays an active role in this process.
Given earlier findings that showed that worms lacking NPR-8 were more resistant to infection and oxidative stress, the researchers believe that the NPR-8-controlled increase in collagen expression boosts the animals’ resistance to stressful conditions such as excessive heat. Their next step is to delve deeper into the underlying mechanisms of how increased collagen production enhances stress resistance.
In addition to Liu and Sellegounder, co-authors on the current study include co-first author and postdoctoral research associate Sankara Naynar Palani and postdoctoral research associate Phillip Wibisono, both of the WSU Elson S. Floyd College of Medicine.

A team at the Technical University of Munich (TUM) has induced stem cells to emulate the development of the human heart. The result is a sort of “mini-heart” known as an organoid. It will permit the study of the earliest development phase of our heart and facilitate research on diseases.
The human heart starts forming approximately three weeks after conception. This places the early phase of heart development in a time when women are often still unaware of their pregnancy. That is one reason why we still have little knowledge of many details of how the heart is formed. Findings from animal studies are not fully transferable to humans. An organoid developed at TUM could prove helpful to researchers.
A ball of 35,000 cells
The team working with Alessandra Moretti, Professor of Regenerative Medicine in Cardiovascular Disease, has developed a method for making a sort of “mini-heart” using pluripotent stem cells. Around 35,000 cells are spun into a sphere in a centrifuge. Over a period of several weeks, different signaling molecules are added to the cell culture under a fixed protocol. “In this way, we mimic the signaling pathways in the body that control the developmental program for the heart,” explains Alessandra Moretti. The group has now published its work in the journal Nature Biotechnology.
First-ever “epicardioids”
The resulting organoids are about half a millimeter in diameter. Although they do not pump blood, they can be stimulated electrically and are capable of contracting like human heart chambers. Prof. Moretti and her team are the first researchers in the world to successfully create an organoid containing both heart muscle cells (cardiomyocytes) and cells of the outer layer of the heart wall (epicardium). In the young history of heart organoids — the first were described in 2021 — researchers had previously created only organoids with cardiomyocytes and cells from the inner layer of the heart wall (endocardium).

“To understand how the heart is formed, epicardium cells are decisive,” says Dr. Anna Meier, first author of the study. “Other cell types in the heart, for example in connecting tissues and blood vessels, are formed from these cells. The epicardium also plays a very important role in forming the heart chambers.” The team has appropriately named the new organoids “epicardioids.”
New cell type discovered
Along with the method for producing the organoids, the team has reported its first new discoveries. Through the analysis of individual cells they have determined that precursor cells of a type only recently discovered in mice are formed around the seventh day of the development of the organoid. The epicardium is formed from these cells. “We assume that these cells also exist in the human body — if only for a few days,” says Prof. Moretti.
These insights may also offer clues as to why the fetal heart can repair itself, a capability almost entirely absent in the heart of an adult human. This knowledge could help to find new treatment methods for heart attacks and other conditions.
Producing “personalized organoids”
The team also showed that the organoids can be used to investigate the illnesses of individual patients. Using pluripotent stem cells from a patient suffering from Noonan syndrome, the researchers produced organoids that emulated characteristics of the condition in a Petri dish. Over the coming months the team plans to use comparable personalized organoids to investigate other congenital heart defects.
With the possibility of emulating heart conditions in organoids, drugs could be tested directly on them in the future. “It is conceivable that such tests could reduce the need for animal experiments when developing drugs,” says Alessandra Moretti.
Organoid research is a key research area at TUM
The researchers have registered an international patent for the process of creating heart organoids. The Epicardioid model is one of several organoid projects at TUM. At the Center for Organoid Systems work groups from various departments and chairs will collaborate. They will conduct interdisciplinary research into pancreas, brain and heart organoids with state-of-the-art imaging and cellular analysis to study the formation of organs, cancer and neurodegenerative diseases and achieve progress for medicine with human 3D systems.

The saliva of mosquitoes infected with dengue viruses contains a substance that thwarts the human immune system and makes it easier for people to become infected with these potentially deadly viruses, new research reveals.
Dengue has spread in recent years to Europe and the Southern United States in addition to longstanding hotspots in tropical and subtropical areas such as Southeast Asia, Africa and Latin America. The new discovery, from a University of Virginia School of Medicine scientist and his collaborators, helps explain why the disease is so easily transmitted and could eventually lead to new ways to prevent infection.
“It is remarkable how clever these viruses are — they subvert mosquito biology to tamp down our immune responses so that infection can take hold,” said Mariano A. Garcia-Blanco, MD, PhD, who recently joined UVA as chair of the Department of Microbiology, Immunology and Cancer Biology. “There is no doubt in my mind that better understanding of the fundamental biology of transmission will eventually lead to effective transmission-blocking measures.”
Further, Garcia-Blanco suspects that researchers will find similar immune-dampening substances accompanying other mosquito-borne infections such as Zika, West Nile and yellow fever. “Our findings are almost certainly going to be applicable to infections with other flaviviruses,” Garcia-Blanco said. “The specific molecules here are unlikely to apply to malaria, but the concept is generalizable to viral infections.”
Understanding Dengue
Approximately half the world’s population is at risk for dengue, and roughly 400 million people are infected every year. Dengue’s symptoms, including fever, nausea and skin rash, are often mistaken for other diseases. Most people will have mild cases, but about 1 in 20 will develop severe illness that can lead to shock, internal bleeding and death. Unfortunately, it’s possible to contract dengue repeatedly, as it is caused by four related viruses transmitted primarily by the Aedes aegypti species of mosquito. There is no treatment, but the new discovery from Garcia-Blanco and his colleagues identifies an important contributor to the disease’s spread as researchers seek to find better ways to combat it.
Garcia-Blanco and his team found that infected mosquitoes’ saliva contained not just the expected dengue virus but a powerful conspirator: molecules produced by the virus that can blunt the body’s immune response. The injection of these molecules, called sfRNAs, during the mosquito bite makes it more likely that the victim will become infected with dengue, the scientists conclude.
“By introducing this RNA at the biting site, dengue-infected saliva prepares the terrain for an efficient infection and gives the virus an advantage in the first battle between it and our immune defenses,” the researchers write in a new scientific paper outlining their findings.
Scientists who study mosquitoes previously had suspected that the insects’ saliva might contain some type of payload to enhance the potential for infection. Garcia-Blanco’s team’s new findings pinpoints one weapon in the viruses’ arsenal and opens the door to finding new ways to help reduce transmission and control the disease’s spread. For now, the best way to avoid getting seriously sick with dengue remains to avoid getting bitten.
“It’s incredible that the virus can hijack these molecules so that their co-delivery at the mosquito bite site gives it an advantage in establishing an infection,” said researcher Tania Strilets, a graduate student with Garcia-Blanco and co-first author of the scientific paper. “These findings provide new perspectives on how we can counteract dengue virus infections from the very first bite of the mosquito.”

Humans have complex social behavior, diverse communication skills, and a capacity for highly developed tool use. Researchers argue that human evolution may resemble the process of animal domestication, where less aggressive animals are favoured. In the same way, human evolution may be the result of natural selection for more prosocial and cooperative individuals. Such individuals are more likely to interact with others and form complex communities, in which they can learn from each other.
“The theory of self-domestication is hard to test,” says first author Limor Raviv. “This is because only one other species besides humans has been argued to be self-domesticated: bonobos.” Could elephants be the first non-primate animal model for self-domestication? Raviv and her colleagues set out to study the similarities between elephants, bonobos, and humans, and followed up with a genetic analysis.
Hallmarks of domestication
The team found that elephants show many hallmarks of domestication. Similar to humans and bonobos, they have low levels of aggression, high levels of empathic and prosocial behaviour, an extended juvenile period, and increased playfulness and curiosity. Elephants form coalitions, ‘babysit’ calves, offer protection and comfort to others, and help dying or ill members of their herds — and even the occasional outsider. There is also evidence that elephants are both self-aware and sensitive to the needs and wants of others.
Another important hallmark is elephants’ ability to learn from each other. Behaviours that are often innate in other animals — such as what to eat or how to raise offspring — are socially transmitted in elephants. Elephants also have a sophisticated multimodal communication system with an extensive vocal repertoire, ranging from trumpets and roars to low-frequency rumbles. For example, elephants in Kenya have different alarm calls for humans and for bees. Their varied and combined calls even show signs of grammar. Finally, the team found several candidate genes associated with domestication in elephants.
Safe environment
The authors propose that self-domestication in elephants could be related to their massive size and relative strength. “This means that elephants are generally less worried about evading or fighting other animals for their survival,” Raviv explains. “This kind of ‘safe environment’ could relax selective pressures for aggression, free cognitive resources, and open up more opportunities for exploration, communication, and play.”
“Our hypothesis of self-domestication in elephants has exciting potential for future research in other species,” concludes Raviv. “It can inform our understanding of the evolution of prosocial behaviour across evolutionarily distant species, providing important insights into convergent evolution.”

A recent study in the Journal of Biological Chemistry revealed the key to a protein that commonly causes blindness. The biological process involves a protein that is essential for transporting toxic compounds out of the eye, similar to a garbage recycling service. The challenge is that, like food and the waste it generates, these compounds are essential for the eye to function properly — until they build up and cause blindness.
The scientists behind the study research a protein transporter, called ABCA4, that lines the edges of specialized photoreceptor cells in the retina and is normally poised to remove toxic, fatty retinal byproducts called N-Ret-PE. Retinal is a derivative of vitamin A, which is found in foods such as leafy green vegetables.
“Retinal is critical for vision,” said Robert Molday, a professor of biochemistry and molecular biology at the University of British Columbia who oversaw the work. “But, it’s also potentially very toxic because it has a very reactive element. So, cells have to be able to balance between using retinal for sustained vision as well as managing its toxicity .”
Mutations in ABCA4 can cause N-Ret-PE buildup, which leads to vision loss in diseases such as Stargardt disease. Stargardt disease is the most common inherited form of macular degeneration and affects approximately 30,000 people nationwide. There is currently no therapy or cure for the disease.
The researchers were interested in finding out how the ABCA4 transporter malfunctions to cause vision loss. They found that a portion of the protein that interacts with N-Ret-PE, known as the binding pocket, is inert in some patients with Stargardt disease. Therefore, the toxic compounds slip out of the ABCA4 transporter and cannot be removed from the retina.
Next, by changing the makeup of ABCA4, the researchers showed they could mimic the effect of the Stargardt mutations.
“We were able to elucidate the mechanism of binding, which paves the way for treatments for Stargardt disease,” Tongzhou Xu, a postdoctoral fellow at UBC and lead author of the study, said.
The team is optimistic that one day there will be a targeted therapeutic for patients with Stargardt disease that may use gene therapy and specialized particles for delivery to the eye. Gene therapy approaches have already been successfully used to correct mutations in a similar transporter, which causes cystic fibrosis.
“We are now applying two types of technologies to alter ABCA4,” Molday said. “One which was developed to specifically correct the DNA with gene-editing approaches. We are coupling that with lipid nanoparticles, which have been used in the COVID-19 vaccine to encapsulate mRNA. So, by combining these two technologies, we envision being able to potentially correct the defects in individuals with Stargardt’s disease that have specific point mutations.”

An abdominal aortic aneurysm (AAA) causes the wall of a person’s aorta, the largest artery in the body, to weaken and bulge outward. If left untreated, it can continue to grow and eventually rupture, which can lead to life-threatening bleeding.
According to some estimates, up to 80% of patients who experience a ruptured AAA will die before they reach the hospital or during surgery. But early intervention can prevent rupture, improve outcomes, and avoid death.
In Physics of Fluids, by AIP Publishing, researchers from the Indian Institute of Technology (BHU) Varanasi and Indian Institute of Technology Kanpur made a computational model of the cardiovascular system in order to predict early AAA rupture and monitor patients’ blood vessel conditions. The team investigated the effect of realistic, patient-specific AAA shapes on the hemodynamics of pulsatile Newtonian fluids in an aortofemoral artery under normal and diseased conditions.
Predicting the risk of AAA rupture involves a combination of imaging studies, such as ultrasound, CT scans, and MRI, and hemodynamics, as well as clinical factors such as age, sex, smoking history, and family history of AAA.
“If an AAA is detected early, treatment options such as surgical repair or endovascular stent grafting are available to prevent rupture,” said the authors. “These treatments are both effective at reducing the risk of rupture and improving survival rates.”
Using image-based computational blood dynamics, the researchers mimicked specific health conditions and investigated various hemodynamic parameters. Their patient-specific geometric models of a human aortofemoral artery were constructed from 3D medical imaging data. To solve the blood flow governing equations under the pulsating conditions caused by the heart’s beating, they used finite element-based simulations.
The team found that aneurysm size alters the blood flow velocity distribution. In addition, flow separation occurs during systolic deceleration, and the vortex begins to travel in the aneurysm sac. Among other complex dynamics, this may influence the blood circulation of lower extremities.
“In the future, such computational work will help in development of digital twins of the cardiovascular system,” said Kumar.
Digital twins are virtual patient representations that receive real-time updates on a variety of data variables and help doctors better forecast disease and choose the best course of therapy.

A team led by engineers at the University of California San Diego has developed a biodegradable polymer system to treat rheumatoid arthritis, an autoimmune and inflammatory disease, by working in concert with the power of the human immune system.
The research builds on increasing clinical interest in modulating the immune system to treat cancers and autoimmune disease, as well as previous work with all-trans retinoic acid (ATRA) which is produced naturally in the body and helps cells grow and develop. By approaching these challenges from the perspective of a biomaterials engineering lab, the team adds two key innovations to previous methods: local release and harnessing the joint microenvironment for sustained effectiveness.
With this method, encapsulated ATRA is injected directly into a joint affected by rheumatoid arthritis, where it remains in effect for at least several weeks. During that time, ATRA transforms disease-causing cells into disease-stopping cells, known as regulatory T cells, which can treat or prevent the disease elsewhere in the body.
“Essentially, our system turns the disease site into a factory that produces regulatory T cells,” said David A. McBride, a chemical engineering graduate student at UC San Diego supervised by nanoengineering professor Nisarg Shah. “It uses a biodegradable biomaterial to facilitate the timed release of ATRA, which reprograms T cells so they can treat disease.”
The research was published in the March 8, 2023 issue of Advanced Science. McBride is a coauthor on the paper.
“This is a very promising line of research utilizing the latest and greatest technology in immunoengineering to combat arthritis,” said Iannis Adamopoulous, an associate professor of medicine at Harvard’s Beth Israel Deaconess Medical Center, Department of Medicine, Division of Rheumatology.

What is ATRA?
ATRA is a small molecule currently FDA approved to treat acute promyelocytic leukemia (APML). Research over the last two decades has suggested that it also has promise in treating autoimmune arthritis and relieving inflammation. However, that method relies on ATRA traveling freely throughout the body, which can cause immunosuppression and potentially significant off-target toxicity, along with other unwanted side effects.
“Previous work established that ATRA has potential in treating autoimmune arthritis, but the route of administration precluded the work from being relevant to clinical translation,” said McBride.
When ATRA is encapsulated using biodegradable materials, it can be injected directly into joints at therapeutic concentrations but as it diffuses out of the joint, it enters circulation at much lower concentrations, minimizing or preventing unwanted effects. Without the controlled release afforded by the biomaterial encapsulation, patients would require multiple injections per day to achieve the same effects, which would be impractical in most cases.
How it works
When the human immune system functions properly, helper T cells patrol the body in search of disease-causing pathogens. When a pathogen is detected, a helper T cell can recruit additional cells to help fight it. “It’s kind of similar to how you might have police cars roaming the city, and when one sees a crime occurring, they call for backup to get the situation under control,” said McBride.

Many autoimmune diseases result from cases of “mistaken identity,” in which these cells attack a perceived danger target that is in fact a part of normally functioning cells in the body. The subsequent proliferation of such pathogenic T cells, which McBride calls “bad apples,” can result from a combination of genetic and environmental factors and wreak havoc on the body when they summon large teams of immune cells for unnecessary standoffs.
For example, “in type 1 diabetes, you have bad apples that call in reinforcements against your pancreas,” said McBride. “In multiple sclerosis, it is against your neurons. In rheumatoid arthritis, it is against your joints. So, your immune system recognizes this as something to be attacked, and it goes and recruits a bunch of additional immune cells to these places and fights a war until all the pathogens are gone. Except that, in this case, it’s not attacking pathogens, but healthy parts of the body.”
Many current approaches block the chemical signals that immune cells use to communicate, effectively preventing the pathogenic T cells from calling in reinforcements without eliminating the “bad apples.” Time-released ATRA reprograms them to act as regulatory T cells, or “good apples.” These cells still have the ability to recognize and activate in the joints, but rather than calling in additional immune cells, they help to resolve the inflammation. In areas such as joints, which aren’t recommended for repeated injections, the sustained-release formulation allows sufficient therapeutic exposure to flip the balance.
ATRA makes lasting modifications to the ability of cellular machinery to read cell DNA, improving the function of the anti-inflammatory regulatory T cells. This treats T cells at the site of disease and generates regulatory T cells specific to that diseased tissue. Then, when these cells move to other disease locations, they can help resolve inflammation and promote healing. Because the cells are specific to the disease, they don’t interfere with normal immune function, allowing them to supplement existing therapies or provide alternatives for patients who need them.
“The coolest part about this is that the treated site of disease, where the bad apples were previously proliferating, now becomes a place that can generate regulators that can now go patrol the body and actually prevent disease,” said McBride.
The limitations of existing approaches
Patients with rheumatoid arthritis are frequently treated with disease-modifying anti-rheumatic drugs (DMARDs) and in many patients this approach works well. However, about a third of patients don’t adequately respond to front-line DMARDs, and they come with some significant disadvantages.
First, while using DMARDs, some patients become more susceptible to infectious disease and exhibit weaker responses to vaccines. In this regard, “the COVID-19 pandemic has brought a lot more understanding on the risks of immunosuppression into public awareness,” said McBride.
Additionally, because most immunosuppressives currently used to treat rheumatoid arthritis stay in the system for up to two weeks, there is no option to discontinue treatment if a dangerous infection occurs. This is compounded when patients use two or more treatments simultaneously, which is not uncommon due to the complexity of the disease. Using multiple powerful immunosuppressants can exacerbate the risks of infections or cancer.
“If you can instead have a treatment option that doesn’t have an immunosuppressive effect, you can really reduce the risk for patients that need multiple treatment modalities to keep their autoimmune disease in check,” McBride said.
Finally, for some patients, immunosuppressives work well for a time and then lose their effectiveness. This can happen when their bodies develop antibodies that neutralize the medications or new disease pathways emerge. New treatments like this one could potentially supplement DMARDs, compensating for waning effectiveness or requiring lower doses to start with.
“In well controlled patients, reducing or eliminating the need for immunosuppressive drugs is desirable,” said Shah. “However, when it is attempted, studies have shown that the disease can flare up again. So having a non-immunosuppressive option could go a long way.”
Research methods, challenges and next steps
The team tested its biomaterial-encapsulation method using a combination of mouse and human cells. After this achieved positive results, they transitioned to mouse models of autoimmune arthritis, coming closer to simulating the remarkable complexity of a real-life case of autoimmune disease in a human subject.
The work required multiple models of disease, each designed to demonstrate a specific aspect of the team’s hypothesis, as well as rigorously tracking the cells from their origin points at injection to the other locations where they recirculated and proved effective in fighting disease.
Currently, the researchers are actively working toward commercialization. “As this is my first experience with something like this, it is difficult for me to estimate, but we are currently targeting approval to start clinical trials within five years,” said McBride. To evaluate possible commercialization routes, McBride has participated in the UC San Diego Institute for the Global Entrepreneur (IGE) NSF I-Corps and MedTech Accelerator programs.
The power of a multidisciplinary approach
When he entered graduate school at UC San Diego, McBride was focused on modeling complex signaling patterns in biological systems, for which rheumatoid arthritis provided many intriguing examples. He became more engaged as he gained awareness of the human side of the disease.
“I’m always surprised at how many people know someone fighting an autoimmune disease or are struggling with one themselves,” he said. “These experiences have really moved it from an interesting problem on paper that I’m trying to solve to a real, difficult problem in the lives of friends and family,”
This research required a highly interdisciplinary approach, relying on input from experts in biomaterials design, immunology, clinical rheumatology and beyond. McBride credits the highly collaborative environment on the UC San Diego campus as a crucial factor in its success.
“UC San Diego doesn’t only promote academic collaboration, but also provides several resources for translating our discoveries beyond the lab and into the clinic,” he said. “Most recently, we are excited to have been awarded a UC San Diego internal grant under the Accelerating Innovations to Market program.”
Shah, McBride and paper co-senior author Nunzio Bottini, MD, PhD, a former Professor of Medicine at UC San Diego, now with Cedars-Sinai Medical Center, received the Accelerating Innovation to Market (AIM) award for 2023. “By including high-caliber industry and investment experts in the selection process, it provides precious validation of the commercial potential of our idea,” Bottini said. “Plus, it supports the laboratory in completing proof of concept validation work needed to accelerate translation.”

Jumping genes are short sections of DNA that have been incorporated randomly into the human genome over the long course of evolution. Also called transposable elements, these pieces of DNA have been implicated in the development of cancer.
But new research from Washington University School of Medicine in St. Louis suggests that transposable elements in various cancers potentially may be used to direct novel immunotherapies to tumors that don’t typically respond to immune-based treatments.
The study is available online in the journal Nature Genetics.
Immunotherapy is often most effective in tumors with numerous mutations, such as skin and lung cancers. Mutations in DNA cause cancer cells to produce unusual proteins that distinguish tumor cells from normal cells and serve as targets — called tumor antigens — for immunotherapies, such as antibodies, vaccines and genetically engineered CAR-T cell therapies. But many tumor types don’t contain large numbers of mutations and are therefore harder for the immune system to identify as a threat.
“Immunotherapy is an extremely promising approach for cancer treatment, but current therapies don’t work in many tumor types in which the mutation burden is low,” said senior author Ting Wang, PhD, the Sanford C. and Karen P. Loewentheil Distinguished Professor of Medicine. “We are excited about this research, because it opens up an entirely new way to identify tumor antigens in types of cancer that have previously been invisible to immunotherapy.”
Jumping genes — believed to have possibly originated from viruses — usually are found in parts of the genome that are inactive in adult tissues. But past work by Wang and his colleagues showed that these transposable elements sometimes can function as hidden on switches, forcing a gene to be turned on all the time, even though it should not be. As these stealthy on switches drive cancer growth, they also can churn out unusual pieces of proteins that are unique to the tumor and not present in normal cells.
In an analysis of 33 tumor types from the National Cancer Institute’s The Cancer Genome Atlas Program, the researchers identified 1,068 transposable element-derived transcripts — or sections of RNA made by the cancer cells — with the potential to produce tumor antigens that could serve as targets for new immunotherapies.
Wang and his colleagues determined that these possible tumor antigens were present on the surfaces of cancer cells, making them ideal for targeting with immunotherapies. Importantly, they found that almost 98% of the more than 10,000 tumors analyzed had at least one potential antigen target arising from a transposable element. Most tumors had from two to 75 possible antigens.
In another important finding, the researchers showed that many of the candidate proteins that could serve as antigens were present in multiple tumors and, in some cases, across tumor types. Wang and his colleagues speculated that this raises the possibility of a universal antigen-based therapy that could treat multiple tumors with a single cocktail targeting several of the most common tumor antigens that arise from jumping genes. For example, the data suggest that a vaccine with a combination of 20 of the most common protein targets could cover about 75% of patients across 27 cancer types.
“With this analysis, we can envision the design of a cancer vaccine that targets the top five or top 10 most common tumor proteins that are caused by transposable elements,” said Wang, also a research member of Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “This type of vaccine is still just an idea, but we are excited about the potential, because these common targets could cover a large fraction of tumors. Much more work is necessary, but we are hopeful that this analysis can serve as a starting point for the development of effective immunotherapies across many more cancer types.”

Over 80% of predicted heat-related deaths in the Middle East and North Africa (MENA) by the end of the century could be prevented if global warming is limited to 2°C, according to a modelling study published in The Lancet Planetary Health.
Under high-emissions scenarios, approximately 123 people per 100,000 in MENA are predicted to die annually from heat-related causes by the end of the century — approximately 60-fold greater than current figures and much higher than predictions under similar scenarios worldwide.
However, if global warming is instead limited to 2°C, over 80% of these deaths could be avoided, highlighting the urgent need for better adaption policies and a switch to renewable technologies.
The findings come as the world prepares for COP28 in Dubai in November.
MENA is one of the most climate-vulnerable regions of the world, with maximum temperatures predicted to rise to almost 50°C by the end of the century, potentially making some areas unliveable.
However, despite this vulnerability, the impact of heat stress in this region, which is worsening due to climate change, remains underexplored.

In the current study, an international team of researchers, including from the London School of Hygiene & Tropical Medicine (LSHTM), modelled current (2001 to 2020) and future (2021 to 2100) trends in heat-related mortality in 19 countries in the MENA region. In their analyses, the team considered variations in the levels of potential greenhouse gas emissions over time and different socioeconomic scenarios.
Under high emissions scenarios (defined by the Intergovernmental Panel on Climate Change Shared Socioeconomic Pathways (SSP) 5-8.5), most of the MENA region will experience substantial levels of warming by the 2060s.
Indeed, under SSP5-8.5, annual heat-related deaths will rise from approximately two per 100,000 currently to 123 per 100,000 by the period between 2081 and 2100. Although current heat-related deaths in MENA are relatively low compared to other regions (two per 100,000 compared to 17 per 100,000 in Western Europe or 10 per 100,000 in Australasia, for example), this rise is expected to be much higher than other regions of the world under similar climate change scenarios. The UK, for example, is expected to see a rise from current figures of three per 100,000 to nine per 100,000 by the 2080s.
Iran is expected to have the highest annual death rate in MENA under SSP5-8.5 (423 per 100,000), with other countries such as Palestine, Iraq and Israel also predicted to have high rates (186, 169 and 163 per 100,000, respectively). Smaller Gulf states, such as Qatar and the United Arab Emirates, will see the greatest relative increases in heat-related deaths.
However, for the MENA region as a whole, if global warming can be limited to 2°C as defined by SSP1-2.6, the team estimate that over 80% of the total 123 annual predicted heat-related deaths per 100,000 people could be avoided.

With COP28 on the horizon, the authors conclude that there is an even greater urgency for stronger mitigation and adaptation policies to be agreed upon, both at the conference and beyond, if MENA is to avoid the worst possible impacts of future warming.
Reliance on traditional heat-adaption solutions such as air-conditioning will not be enough, they warn. Air-conditioning, for example, is used to a relatively high extent in countries where rates of heat-related mortality are higher than the regional average, such as in Israel and Cyprus.
As population growth in MENA will be a substantial driver of predicted heat-related deaths, demographic policies and healthy ageing will also be vital if MENA is to successfully adapt to a changing climate.
Shakoor Hajat, lead author and Professor of Global Environmental Health at LSHTM, said: “Global warming will need to be limited to 2°C to avoid the catastrophic health impacts estimated in our study. Even with stronger action, countries in the region need to develop ways other than air-conditioning to protect their citizens from the dangers of extreme heat.
“Strengthening health systems and better coordination between MENA countries will be key in tackling the health impacts of climate change in the region. With COP28 coming up, discussions are needed to consider how countries in the region can better work together to improve resilience in the face of climate change.”