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Researchers at the AIDS Institute, Department of Microbiology, School of Clinical Medicine, and the State Key Laboratory of Emerging Infectious Diseases, LKS Faculty of Medicine of the University of Hong Kong (HKUMed), in collaboration with HKU-Shenzhen Hospital, Foshan University and The Third People’s Hospital of Shenzhen, found that PD-1-enhanced DNA vaccination can induce sustained virus-specific CD8+ T cell immunity in an AIDS monkey model. The vaccinated monkeys remained free of AIDS for six years and achieved virologic control without the need for combination antiretroviral therapy (cART), a treatment used to suppress viral replication in individuals living with human immunodeficiency virus (HIV).
The study also found that polyfunctional and broadly reactive effector-memory virus-specific T cells were maintained in the protected experimental macaques for over six years. The findings provide supporting evidence that the PD-1-enhanced DNA vaccine strategy holds promise as a third-generation DNA vaccine for AIDS prevention and immunotherapy. The peer-reviewed study was published in the journal Microbiology Spectrum, by The American Society for Microbiology.
Background
Using cART for both pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) contributes efficiently to reducing AIDS-related deaths and HIV-1 transmission cases. Despite the effectiveness of cART, HIV-1 can persist in latent reservoirs. This has made it challenging to achieve complete or sustained cART-free virologic control of HIV-1 infection for the past 40 years since the discovery of AIDS and its causative agent HIV-1 in the early 1980s. Moreover, the extensive HIV-1 genetic diversity facilitates the formation of mutational escape variants that resist cART drugs, resulting in the clinical failure of viral control. The huge number of viral variants also hampers AIDS vaccine development. Identifying novel vaccination strategies, including the induction of robust cross-reactive T cell responses, will enhance the arsenal against HIV/ AIDS epidemic.
Research methods and findings
The researchers developed a vaccine technology known as the programmed death-1 (PD-1)-enhanced DNA vaccine strategy, which involves using a DNA vector to encode specific antigens fused with the soluble domain of PD-1 protein. Our previous murine studies found that this strategy allows more efficient antigen delivery targeting to professional antigen-presenting cells, called dendritic cells. It results in the superiority of immunogenicity and the protective efficacy against both viral infection and tumorigenesis over conventional vaccines. Notably, PD-1-enhanced DNA vaccines elicit strong CD8+ T cell responses.
In 2021, the researchers reported the findings of a rhesus monkey study, which evaluated the potential of a PD-1-enhanced DNA vaccine against the simian — human immunodeficiency virus (SHIV). The rhesus monkeys were vaccinated with a DNA vaccine, pRhPD1-p27, designed based on the PD-1-enhanced DNA vaccine strategy. The vaccine resulted in sustained virological control against pathogenic SHIVSF162P3CN challenge, which was mediated by a strong polyfunctional vaccine-induced effector-memory CD8+ T cell response. In a group of four pRhPD1-p27-vaccinated macaques, an aviremic state (absence of detectable virus in the blood) was maintained for two years, indicating that potential cART-free virologic control could be achievable with the PD-1-enhanced DNA vaccine. The recent follow-up study demonstrated extended cART-free virologic control for over six years.
Efficient strategies for HIV-1 cART-free virologic control are crucial for ending the AIDS epidemic. ‘Our innovative PD-1-enhanced DNA vaccine was effective not only in inducing polyfunctional effector-memory CD8+ T cells for AIDS prevention in rhesus monkeys, but also in sustaining cART-free virologic control for over six years,’ remarked Professor Chen Zhiwei, Director of the AIDS Institute and Chair Professor of the Department of Microbiology, School of Clinical Medicine, HKUMed, who led the study. ‘The encouraging outcomes validate the continuation of ongoing clinical trials investigating the potential of the PD-1-enhanced DNA vaccine for achieving HIV-1 cART-free virologic control. Hopefully, the vaccine can be employed independently or in conjunction with other biomedical interventions for individuals living with the virus in the future.’
If this efficacy can be replicated in humans, a therapeutic vaccine for cART-free HIV-1 control will be on the horizon. Currently, a Phase I clinical trial, in which the HKUMed team is collaborating with The Third People’s Hospital of Shenzhen to test whether the non-human primate data can be replicated in humans, is underway. The report of the trial results is expected to be available in the second quarter this year.

For the first time, researchers from The University of Queensland (UQ) have mapped out the proteins implicated in the early stages of motor neurone disease (MND).
Dr Rebecca San Gil from Associate Professor Adam Walker’s lab at UQ’s Queensland Brain Institute has developed a longitudinal map of the proteins involved in MND across the trajectory of the disease, identifying potential therapeutic pathways for further investigation.
“The map is a springboard for many more projects exploring the proteins activated and repressed during the onset, early and late stages of MND,” Dr San Gil said.
“These proteins are biological factors that drive disease onset and progress its development over time.
“We measured differences in protein levels in the brain across the trajectory of the disease and collated this information into a longitudinal map.”
The map is now available for scientists worldwide and will accelerate investigations into MND.
Dr San Gil has been working in mouse models of MND to understand the mechanisms driving TDP-43 pathology in the brain, which accounts for 95% of amyotrophic lateral sclerosis (ALS) cases and 50% of frontotemporal lobar degeneration (FTLD).

Building on the mapping project, Dr San Gil chose to focus on a protein-folding factor called DNAJB5.
“Before the onset of MND in mouse models, we observed a marked increase in protein groups responsible for physically assisting in the protein folding process.
“One of these ‘chaperone’ proteins, DNAJB5, was particularly abundant early on, sparking our curiosity about its role in disease progression.
“In human brain tissue, we found DNAJB5 enriched in areas where TDP-43 aggregates.
“The short-term elevation of DNAJB5 is likely a protective mechanism by neurons in an attempt to control TDP-43 as it begins to dysfunction.
“This protective response to TDP-43 needs further investigation because it may help us identify preventative and therapeutic approaches to MND.”
A/ Prof Walker envisions that the lab will continue to follow other identified protein pathways, using gene therapy and repurposing medicine, to see if they can alter or prevent the disease.
This paper was published in Nature Communications.
Compiling the TDP map was a collaborative project with researchers from Macquarie University, the University of Auckland, and the Children’s Medical Research Institute.

Society learned about the value of mRNA during the COVID-19 pandemic when we saw scientists and medical professionals harness its power to deliver a vaccine for the virus within a year.
Now, University of Waterloo pharmacy associate professor Emmanuel Ho has developed a novel nanomedicine loaded with genetic material called small interfering RNAs (siRNA) to fight human immunodeficiency virus (HIV) using gene therapy. These siRNAs regulate which genes or proteins are turned on or off in our cells and showed a 73 per cent reduction in HIV replication.
“This opens the door for new therapeutics in the fight against HIV,” said Dr. Ho, who is among Waterloo’s researchers and entrepreneurs leading health innovation in Canada.
Autophagy, also known as the body’s recycling process, plays an important role in our body to eliminate microbes such as viruses and bacteria inside cells. HIV is quite smart and produces a protein, Nef, that prevents cells from activating autophagy.
This is the first research to develop a combination nanomedicine that can reactivate autophagy and prevent HIV entry into cells, allowing our body to re-initiate its defence system.
Additionally, HIV has a gene, CCR5, that allows the virus to enter a cell. The siRNAs target both Nef and CCR5 to reduce HIV infection.
This nanomedicine is intended to be applied vaginally to protect against sexual transmission of HIV. As a result, the nanomedicine is designed to be stable without leakage of siRNAs in the acidic vaginal environment but release the siRNA once inside cells.
“Viruses are smart. They produce Nef proteins to prevent autophagy from occurring,” Ho said. “Our process allows our body to fight the viral infection without needing additional drugs,”
Ho confirms that the next steps include further optimizing the process and improving our understanding of how autophagy plays a role in how our cells protect us from viruses.
“We also hope this will shed some light to develop more alternative approaches to effectively reduce antimicrobial resistance,” Ho said.

Drugs that treat conditions like depression and anxiety often come with varying side effects, as they regulate various functions within the human body at the same time. What if these drugs could activate only the functions that target the specific conditions that they are designed to treat?
A team of researchers has found a potential way to treat these conditions with fewer side effects. Led by Professor Gavin Dawe, Head of the Department of Pharmacology at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), the team conducted modifications of relaxin-3 — a neuropeptide, or molecule, found mainly in the human brain and nervous system — which regulates a wide range of physiological functions, including stress responses, appetite, mood and pain perception. When relaxin-3 is released in the brain, it binds to a target receptor RXFP3 — to trigger a variety of signalling responses among the cells, which affect the body’s physiological processes.
However, as RXFP3 is involved in many different functions, a drug developed to treat certain conditions may cause unwanted side effects — because several of RXFP3’s signalling pathways are activated at the same time. For example, a drug that treats depression may cause adverse effects related to another function, such as feeding behaviour, which is related to eating disorders and obesity. The receptor has also been demonstrated in much existing research, including earlier work by Prof Dawe, to be a potential new target for drugs to treat these conditions. To develop better drug treatments with fewer side effects, the key is to activate only specific signalling pathways of RXFP3 that target specific conditions.
Prof Dawe’s team modified the relaxin-3 molecules, such that they activated only a part of the RXFP3 response in their interaction, instead of all the different signalling pathways. Their work, published in Science Signaling, is the first discovery that modifications of relaxin-3 can lead to selective activation of some RXFP3-led signalling pathways, which is a mechanism known as biased agonism.
Prof Dawe said, “Our study has pointed to potential ways of developing drugs by modifying relaxin-3, or other neuropeptides, that can selectively activate specific functions within the body. This is important as it means drugs could be designed to have more specific effects and less undesired, adverse effects, making them more effective in managing a range of conditions like anxiety, depression, eating disorders, obesity, and addiction.”
Through a technique known as peptide stapling, the research team modified the B-chain of relaxin-3, replacing blocks of amino acids within them with artificial ones that introduce ‘chemical bridges’ between them. Alone, the B-chain is highly flexible and can twist and bend into many different shapes, reducing its ability to be stabilised for more effective binding and activation of the receptor RXFP3. The stapling process locks the shape of the specific B-chain in relaxin-3, stabilising it for a more efficient interaction with the receptor RXFP3, where it triggers certain signalling pathways in the brain that affect the body’s physiological functions.
Dr Tharindunee Jayakody, first author of the study and PhD alumna of the Department of Pharmacology at NUS Medicine, said, “We are at very early stages in terms of the journey in making clinically useful drugs. However, the promising findings from our study are a significant step in our aspiration to separately design stapled peptides that have selective effects on anxiety, depression, eating disorders and addiction. Our collaborative work would also strive to understand how proteins like RXFP3 function at a molecular level, with the help of biased agonists.” She is leading a team of researchers to understand the molecular properties of proteins such as RXFP3 at the Department of Chemistry, Faculty of Science, University of Colombo, Sri Lanka, where she is a lecturer in biochemistry and molecular biology.
With the conclusion of the study, the research team plans to use different stapled peptides to understand how the signalling functions, activated by the interactions between relaxin-3 and RXFP3, affect the body’s physiological functions and human behaviour.

The recent approval of a CRISPR-Cas9 therapy for sickle cell disease demonstrates that gene editing tools can do a superb job knocking out genes to cure hereditary disease. But it’s still not possible to insert whole genes into the human genome to substitute for defective or deleterious genes.
A new technique that employs a retrotransposon from birds to insert genes into the genome holds more promise for gene therapy, since it inserts genes into a “safe harbor” in the human genome where the insertion won’t disrupt essential genes or lead to cancer.
Retrotransposons, or retroelements, are pieces of DNA that, when transcribed to RNA, code for enzymes that copy RNA back into DNA in the genome — a self-serving cycle that clutters the genome with retrotransposon DNA. About 40% of the human genome is made up of this “selfish” new DNA, though most of the genes are disabled, so-called junk DNA.
The new technique, called Precise RNA-mediated INsertion of Transgenes, or PRINT, leverages the ability of some retrotransposons to efficiently insert entire genes into the genome without affecting other genome functions. PRINT would complement the recognized ability of CRISPR-Cas technology to disable genes, make point mutations and insert short segments of DNA.
A description of PRINT, which was developed in the laboratory of Kathleen Collins, a professor of molecular and cell biology at the University of California, Berkeley, will be published Feb. 20 in the journal Nature Biotechnology.
PRINT involves the insertion of new DNA into a cell using delivery methods similar to those used to ferry CRISPR-Cas9 into cells for genome editing. For PRINT, one piece of delivered RNA encodes a common retroelement protein called R2 protein, which has multiple active parts, including a nickase — an enzyme that binds and nicks double-stranded DNA — and reverse transcriptase, the enzyme that generates the DNA copy of RNA. The other RNA is the template for the transgene DNA to be inserted, plus gene expression control elements — an entire autonomous transgene cassette that R2 protein inserts into the genome, Collins said.
A key advantage of using R2 protein is that it inserts the transgene into an area of the genome that contains hundreds of identical copies of the same gene — each coding for ribosomal RNA, the RNA machine that translates messenger RNA (mRNA) into protein. With so many redundant copies, when the insertion disrupts one or a few ribosomal RNA genes, the loss of the genes won’t be missed.

Putting the transgene into a safe harbor avoids a major problem encountered when inserting transgenes via a human virus vector, which is the common method today: The gene is often inserted randomly into the genome, disabling working genes or messing with the regulation or function of genes, potentially leading to cancer.
“A CRISPR-Cas9-based approach can fix a mutant nucleotide or insert a little patch of DNA — sequence fixing. Or you can just knock out a gene function by site-specific mutagenesis,” said Collins, who holds the Walter and Ruth Schubert Family Chair. “We’re not knocking out a gene function. We’re not fixing an endogenous gene mutation. We’re taking a complementary approach, which is to put into the genome an autonomously expressed gene that makes an active protein — to add back a functional gene as a deficit bypass. It’s transgene supplementation instead of mutation reversal. To fix loss-of-function diseases that arise from a panoply of individual mutations of the same gene, this is great.”
‘The real winners were from birds’
Many hereditary diseases, such as cystic fibrosis and hemophilia, are caused by a number of different mutations in the same gene, all of which disable the gene’s function. Any CRISPR-Cas9-based gene editing therapy would have to be tailored to a person’s specific mutation. Gene supplementation using PRINT could instead deliver the correct gene to every person with the disease, allowing each patient’s body to make the normal protein, no matter what the original mutation.
Many academic labs and startups are investigating the use of transposons and retrotransposons to insert genes for gene therapy. One popular retrotransposon under study by biotech companies is LINE-1 (Long INterspersed Element-1), which in humans has duplicated itself and some hitchhiker genes to cover about 30% of the genome, though fewer than 100 of our genome’s LINE-1 retrotransposon copies are functional today, a miniscule fraction of the genome.
Collins, along with UC Berkeley postdoctoral colleague Akanksha Thawani and Eva Nogales, UC Berkeley Distinguished Professor in the Department of Molecular and Cell Biology and a Howard Hughes Medical Institute investigator, published a cryoelectron microscopy structure of the enzyme protein encoded by the LINE-1 retroelement on Dec. 14 in the journal Nature.

That study made it clear, Collins said, that the LINE-1 retrotransposon protein would be hard to engineer to safely and efficiently insert a transgene into the human genome. But previous research demonstrating that genes inserted into the repetitive, ribosomal RNA encoding region of the genome (the rDNA) get expressed normally suggested to Collins that a different retroelement, called R2, might work better for safe transgene insertion.
Because R2 is not found in humans, Collins and senior researcher Xiaozhu Zhang and postdoctoral fellow Briana Van Treeck, both from UC Berkeley, screened R2 from more than a score of animal genomes, from insects to the horseshoe crab and other multicellular eukaryotes, to find a version that was highly targeted to rDNA regions in the human genome and efficient at inserting long lengths of DNA into the region.
“After chasing dozens of them, the real winners were from birds,” Collins said, including the zebra finch and the white-throated sparrow.
While mammals do not have R2 in their genomes, they do have the binding sites needed for R2 to effectively insert as a retroelement — likely a sign, she said, that the predecessors to mammals had an R2-like retroelement that somehow got kicked out of the mammalian genome.
In experiments, Zhang and Van Treeck synthesized mRNA-encoding R2 protein and a template RNA that would generate a transgene with a fluorescent protein expressed by an RNA polymerase promoter. These were cotransfected into cultured human cells. About half the cells lit up green or red due to fluorescent protein expression under laser light, demonstrating that the R2 system had successfully inserted a working fluorescent protein into the genome.
Further studies showed that the transgene did indeed insert into the rDNA regions of the genome and that about 10 copies of the RNA template could insert without disrupting the protein-manufacturing activity of the rDNA genes.
A giant ribosome biogenesis center
Inserting transgenes into rDNA regions of the genome is advantageous for reasons other than it gives them a safe harbor. The rDNA regions are found on the stubby arms of five separate chromosomes. All of these stubby arms huddle together to form a structure called the nucleolus, in which DNA is transcribed into ribosomal RNA, which then folds into the ribosomal machinery that makes proteins. Within the nucleolus, rDNA transcription is highly regulated, and the genes undergo quick repairs, since any rDNA breaks, if left to propagate, could shut down protein production. As a result, any transgene inserted into the rDNA region of the genome would be treated with kid gloves inside the nucleolus.
“The nucleolus is a giant ribosome biogenesis center,” Collins said. “But it’s also a really privileged DNA repair environment with low oncogenic risk from gene insertion. It’s brilliant that these successful retroelements — I’m anthropomorphizing them — have gone into the ribosomal DNA. It’s multicopy, it’s conserved, and it’s a safe harbor in the sense that you can disrupt one of these copies and the cell doesn’t care.”
This makes the region an ideal place to insert a gene for human gene therapy.
Collins admitted that a lot is still unknown about how R2 works and that questions remain about the biology of rDNA transcription: How many rDNA genes can be disrupted before the cell cares? Because some cells turn off many of the 400+ rDNA genes in the human genome, are these cells more susceptible to side effects of PRINT? She and her team are investigating these questions, but also tweaking the various proteins and RNAs involved in retroelement insertion to make PRINT work better in cultured cells and primary cells from human tissue.
The bottom line, though, is that “it works,” she said. “It’s just that we have to understand a little bit more about the biology of our rDNA in order to really take advantage of it.”
Other co-authors of the Nature Biotechnology paper are UC Berkeley graduate students Connor Horton, Jeremy McIntyre, Sarah Palm and Justin Shumate. The work was supported by the National Institutes of Health (F32 GM139306, DP1 HL156819, T32 GM07232) and the Shurl and Kay Curci Foundation. Collins has filed for patents on PRINT, and co-founded a company, Addition Therapeutics, to develop PRINT further as a gene therapy.

Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat in humans, resulting in a lower biological age, according to a new USC Leonard Davis School of Gerontology-led study.
The study, which appears in Nature Communications on Feb. 20, adds to the body of evidence supporting the beneficial effects of the fasting-mimicking diet (FMD).
The FMD is a five-day diet high in unsaturated fats and low in overall calories, protein, and carbohydrates and is designed to mimic the effects of a water-only fast while still providing necessary nutrients and making it much easier for people to complete the fast. The diet was developed by the laboratory of USC Leonard Davis School Professor Valter Longo, the senior author of the new study.
“This is the first study to show that a food-based intervention that does not require chronic dietary or other lifestyle changes can make people biologically younger, based on both changes in risk factors for aging and disease and on a validated method developed by the Levine group to assess biological age,” Longo said.
Previous research led by Longo has indicated that brief, periodic FMD cycles are associated with a range of beneficial effects. They can: Promote stem cell regeneration Lessen chemotherapy side effects Reduce the signs of dementia in miceIn addition, the FMD cycles can lower the risk factors for cancer, diabetes, heart disease and other age-related diseases in humans.
The Longo lab also had previously shown that one or two cycles of the FMD for five days a month increased the healthspan and lifespan of mice on either a normal or Western diet, but the effects of the FMD on aging and biological age, liver fat, and immune system aging in humans were unknown until now.

Lower disease risks & more youthful cells
The study analyzed the diet’s effects in two clinical trial populations, each with men and women between the ages of 18 and 70. Patients who were randomized to the fasting-mimicking diet underwent 3-4 monthly cycles, adhering to the FMD for 5 days, then ate a normal diet for 25 days.
The FMD is comprised of plant-based soups, energy bars, energy drinks, chip snacks, and tea portioned out for 5 days as well as a supplement providing high levels of minerals, vitamins, and essential fatty acids. Patients in the control groups were instructed to eat either a normal or Mediterranean-style diet.
An analysis of blood samples from trial participants showed that patients in the FMD group had lower diabetes risk factors, including less insulin resistance and lower HbA1c results. Magnetic resonance imaging also revealed a decrease in abdominal fat as well as fat within the liver, improvements associated with a reduced risk of metabolic syndrome. In addition, the FMD cycles appeared to increase the lymphoid-to-myeloid ratio — an indicator of a more youthful immune system.
Further statistical analysis of the results from both clinical studies showed that FMD participants had reduced their biological age — a measure of how well one’s cells and tissues are functioning, as opposed to chronological age — by 2.5 years on average.
“This study shows for the first time evidence for biological age reduction from two different clinical trials, accompanied by evidence of rejuvenation of metabolic and immune function,” Longo said.
The study, conducted by first authors Sebastian Brandhorst, USC Leonard Davis research associate professor, and Morgan E. Levine, founding principal investigator of Altos Labs and USC Leonard Davis PhD alumna, lends more support to the FMD’s potential as a short-term periodic, achievable dietary intervention that can help people lessen their disease risk and improve their health without extensive lifestyle changes, Longo said.
“Although many doctors are already recommending the FMD in the United States and Europe, these findings should encourage many more healthcare professionals to recommend FMD cycles to patients with higher than desired levels of disease risk factors as well as to the general population that may be interested in increased function and younger age,” Longo said.

Any drug that is taken orally must pass through the lining of the digestive tract. Transporter proteins found on cells that line the GI tract help with this process, but for many drugs, it’s unknown which of those transporters they use to exit the digestive tract.
Identifying the transporters used by specific drugs could help to improve patient treatment because if two drugs rely on the same transporter, they can interfere with each other and should not be prescribed together.
Researchers at MIT, Brigham and Women’s Hospital, and Duke University have now developed a multipronged strategy to identify the transporters used by different drugs. Their approach, which makes use of both tissue models and machine-learning algorithms, has already revealed that a commonly prescribed antibiotic and a blood thinner can interfere with each other.
“One of the challenges in modeling absorption is that drugs are subject to different transporters. This study is all about how we can model those interactions, which could help us make drugs safer and more efficacious, and predict potential toxicities that may have been difficult to predict until now,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study.
Learning more about which transporters help drugs pass through the digestive tract could also help drug developers improve the absorbability of new drugs by adding excipients that enhance their interactions with transporters.
Former MIT postdocs Yunhua Shi and Daniel Reker are the lead authors of the study, which appears today in Nature Biomedical Engineering.
Drug transport
Previous studies have identified several transporters in the GI tract that help drugs pass through the intestinal lining. Three of the most commonly used, which were the focus of the new study, are BCRP, MRP2, and PgP.

For this study, Traverso and his colleagues adapted a tissue model they had developed in 2020 to measure a given drug’s absorbability. This experimental setup, based on pig intestinal tissue grown in the laboratory, can be used to systematically expose tissue to different drug formulations and measure how well they are absorbed.
To study the role of individual transporters within the tissue, the researchers used short strands of RNA called siRNA to knock down the expression of each transporter. In each section of tissue, they knocked down different combinations of transporters, which enabled them to study how each transporter interacts with many different drugs.
“There are a few roads that drugs can take through tissue, but you don’t know which road. We can close the roads separately to figure out, if we close this road, does the drug still go through? If the answer is yes, then it’s not using that road,” Traverso says.
The researchers tested 23 commonly used drugs using this system, allowing them to identify transporters used by each of those drugs. Then, they trained a machine-learning model on that data, as well as data from several drug databases. The model learned to make predictions of which drugs would interact with which transporters, based on similarities between the chemical structures of the drugs.
Using this model, the researchers analyzed a new set of 28 currently used drugs, as well as 1,595 experimental drugs. This screen yielded nearly 2 million predictions of potential drug interactions. Among them was the prediction that doxycycline, an antibiotic, could interact with warfarin, a commonly prescribed blood-thinner. Doxycycline was also predicted to interact with digoxin, which is used to treat heart failure, levetiracetam, an antiseizure medication, and tacrolimus, an immunosuppressant.
Identifying interactions
To test those predictions, the researchers looked at data from about 50 patients who had been taking one of those three drugs when they were prescribed doxycycline. This data, which came from a patient database at Massachusetts General Hospital and Brigham and Women’s Hospital, showed that when doxycycline was given to patients already taking warfarin, the level of warfarin in the patients’ bloodstream went up, then went back down again after they stopped taking doxycycline.

That data also confirmed the model’s predictions that the absorption of doxycycline is affected by digoxin, levetiracetam, and tacrolimus. Only one of those drugs, tacrolimus, had been previously suspected to interact with doxycycline.
“These are drugs that are commonly used, and we are the first to predict this interaction using this accelerated in silico and in vitro model,” Traverso says. “This kind of approach gives you the ability to understand the potential safety implications of giving these drugs together.”
In addition to identifying potential interactions between drugs that are already in use, this approach could also be applied to drugs now in development. Using this technology, drug developers could tune the formulation of new drug molecules to prevent interactions with other drugs or improve their absorbability. Vivtex, a biotech company co-founded in 2018 by former MIT postdoc Thomas von Erlach, MIT Institute Professor Robert Langer, and Traverso to develop new oral drug delivery systems, is now pursuing that kind of drug-tuning.
The research was funded in part by the National Institutes of Health, the Department of Mechanical Engineering at MIT, and the Division of Gastroenterology at Brigham and Women’s Hospital.

Researchers have developed a revolutionary biosensor using terahertz (THz) waves that can detect skin cancer with exceptional sensitivity, potentially paving the way for earlier and easier diagnoses. Published in the IEEE Transactions on Biomedical Engineering, the study presents a significant advancement in early cancer detection, thanks to the collaboration of multidisciplinary teams from Queen Mary University of London and the University of Glasgow.
“Traditional methods for detecting skin cancer often involve expensive, time-consuming, CT, PET scans and invasive higher frequencies technologies,” explains Dr Shohreh Nourinovin, Postdoctoral Research Associate at Queen Mary’s School of Electronic Engineering and Computer Science, and the study’s first author. “Our biosensor offers a non-invasive and highly efficient solution, leveraging the unique properties of THz waves — a type of radiation with lower energy than X-rays, thus safe for humans — to detect subtle changes in cell characteristics.”
The key innovation lies in the biosensor’s design. Featuring tiny, asymmetric resonators on a flexible substrate, it can detect subtle changes in the properties of cells. Unlike traditional methods that rely solely on refractive index, this device analyses a combination of parameters, including resonance frequency, transmission magnitude, and a value called “Full Width at Half Maximum” (FWHM). This comprehensive approach provides a richer picture of the tissue, allowing for more accurate differentiation between healthy and cancerous cells and to measure malignancy degree of the tissue.
In tests, the biosensor successfully differentiated between normal skin cells and basal cell carcinoma (BCC) cells, even at different concentrations. This ability to detect early-stage cancer holds immense potential for improving patient outcomes.
“The implications of this study extend far beyond skin cancer detection,” says Dr Nourinovin. “This technology could be used for early detection of various cancers and other diseases, like Alzheimer’s, with potential applications in resource-limited settings due to its portability and affordability.”
Dr Nourinovin’s research journey wasn’t without its challenges. Initially focusing on THz spectroscopy for cancer analysis, her project was temporarily halted due to the COVID-19 pandemic. However, this setback led her to explore the potential of THz metasurfaces, a novel approach that sparked a new chapter in her research.
Professor Qammer H. Abbasi, Co-director for Communication Sensing & Imaging Hub at University of Glasgow’s James Watt School of Engineering said: “Integrating terahertz imaging technology into this type of flexible, portable, reuseable sensor could make cancer screening a quicker and more comfortable procedure for patients. We’re excited to build on the potential of this breakthrough technology with future collaborative research.
“Despite the initial difficulties, the potential impact of this technology kept us motivated,” says Professor Akram Alomainy, Head of the Antennas & Electromagnetics Research Group at Queen Mary. “We believe this biosensor has the potential to save countless lives by enabling early detection and intervention for various cancers.”

Returning to moderate to vigorous physical activity (MVPA) after a concussion may play a vital role in helping teens feel less anxious while recovering from the injury, according to a new study from researchers in the Department of Orthopedics at the University of Colorado School of Medicine.
Experts estimate around 20% of adolescents have been diagnosed with at least one concussion in their lifetime. Managing symptoms — which can be physical, cognitive, and emotional — is important and means learning more about how mental health can lead to better health outcomes after concussion.
“Independent of concussion, people who exercise more tend to have less anxiety, so it’s not surprising that the same thing would be seen after concussion,” says Katherine Smulligan, PT, DPT, and PhD candidate, lead author of the study.
She and her colleagues at the Colorado Concussion Research Laboratory say patients commonly believe that they should be sedentary and avoid physical activity altogether after experiencing a concussion, but a growing body of research points to that not being necessary in many cases.
While the researchers say that post-concussion anxiety is multifactorial and physical activity isn’t the only variable that influences mental health, they observed a correlation between more time spent in MVPA during the recovery process and less self-reported anxiety symptoms at a follow-up evaluation.
“MVPA performed in the subacute period after concussion predicted lower self-reported anxiety ratings at a follow-up,” they write in their findings published in the journal Medicine and Science in Sports and Exercise. “…A higher intensity of physical activity than is frequently prescribed as standard-of-care during concussion recovery may be beneficial for those experiencing anxiety symptoms after concussion.”
Why anxiety matters
Researchers have previously observed an association between mental health problems in adolescents and concussion, although the cause/effect relationship is not known. This new paper may act as a guideline to help prevent potential post-concussion anxiety by showing that returning to exercise can have benefits.

“If you’re a high school athlete and you’re used to exercising a moderate to vigorous level every day without a concussion and you’re put in a dark room to rest, you may be anxious, drowsy, or have trouble sleeping because of that activity modification,” says David Howell, PhD, ATC, associate professor of orthopedics and director of the Colorado Concussion Research Laboratory. “A teen’s whole life may be uprooted, so we honed in on what happens in this situation when a concussion is part of the equation.”
Addressing anxiety in the concussion recovery process can have an impact on schoolwork, relationships, and general well-being. Researchers also acknowledged that concussion can intensify mental health issues that existed before the injury. These patients are “more likely to develop persistent symptoms compared to those without a pre-injury anxiety history.”
“As such, interventions to help manage anxiety may be beneficial in promoting recovery and improving mental health outcomes after concussion,” the researchers write.
Uncovering new evidence for better care
There’s still more research needed to determine exactly how much physical activity is most beneficial for recovery and how soon patients should return to moderate to vigorous exercise.
The 48 participants in the study were given wrist-worn activity monitors to track their physical activity, but not specific recommendations on what kinds of exercise they should do. That guidance was left to the participant’s treating physician. Researchers tracked MVPA based on percentage of age predicted max heart rate recorded by the monitor.

On average, for every hour engaged in MVPA during the activity monitoring week, anxiety scores according to the PROMIS anxiety T-score decreased by 5.3 points.
“The biggest questions to focus on next is to what intensity should a person exercise after a concussion, and how much and how soon,” Smulligan says. Currently, care standards recommend one to two days of rest following the concussion.
“There is so much in the body that can be affected by concussion, and everybody experiences symptoms a little differently, so it can be hard to study,” Howell adds. “That means we must design studies that focus on understanding specific relationships and associations in a rigorous manner. Over time, when we do enough studies, we can begin to replicate findings and put a whole story together that can help inform best practices and standard of care.”

Our immune system is remarkably powerful. It quickly assembles teams of cells to eliminate threats inside our bodies. But sometimes, it hits the wrong target. Autoimmune diseases like lupus and multiple sclerosis result from friendly fire — immune cells attacking healthy tissues and organs by mistake. New treatments and therapeutic targets are direly needed for these conditions.
Now, Cold Spring Harbor Laboratory (CSHL) Professor Christopher Vakoc may have stumbled upon a new therapeutic target — one hidden in plain sight. Vakoc and his team discovered that IκBζ, a well-studied protein in the immunology field, contains an overlooked sequence, which lets it activate key proteins in immune cells. While the sequence — the OCA peptide — is tiny, targeting it may have significant effects in reeling in immune cells gone haywire.
For years, IκBζ was known for one important job — controlling NFκB, a protein that’s crucial for mounting an immune response. But it turns out IκBζ has dual functions. Vakoc’s team found it also activates another important family of immune proteins called POUs. And it does this through the OCA peptide. Firing up both immune reactions may ensure the quickest response to encroaching dangers — a vital trademark of our natural defenses.
“The immune system is held in check most of the time,” Vakoc says. “But the moment a pathogen arrives, it needs to very quickly adapt. The ability to respond within seconds is critical to eliminating bacteria, an invading virus, or even cancer. Time is of the essence.”
Why has evolution assigned IκBζ this moonlight job? Vakoc suspects it has something to do with the enormous number of tasks immune systems perform. While immune cells activate many of the same proteins, each cell also has its own duties. The duality of IκBζ might provide our body’s defenders the versatility to rapidly switch between roles.
“Evolution often finds creative and efficient solutions to problems in life,” Vakoc explains. “We think the OCA peptide allows different types of immune cells to respond quickly, with the right genes at the right time and place. It’s all about personalizing the immune response for different cells in the body.”
The discovery might form the basis for future immunotherapies against autoimmune disorders. Since the OCA peptide is well-defined and found in many immune cells, it could make for a prime drug target. And that’s where Vakoc will set his sights next.
“Targeting IκBζ via its OCA peptide would be expected to have interesting impacts on the immune system, with highly cell-type-specific effects,” Vakoc says. “Our future research will explore this question.”