Mystery solved: New study reveals how DNA repair genes play a major role in Huntington's disease

Dr. Xiangdong William Yang
Photo Credit: Courtesy of UCLA/Health

A new UCLA Health study has discovered in mouse models that genes associated with repairing mismatched DNA are critical in eliciting damages to neurons that are most vulnerable in Huntington's disease and triggering downstream pathologies and motor impairment, shedding light on disease mechanisms and potential new ways to develop therapies. 

Huntington’s disease is one of the most common inherited neurodegenerative disorders that typically begins in adulthood and worsens over time. Patients begin to lose neurons in specific regions of the brain responsible for movement control, motor skill learning, language and cognitive function. Patients typically live 15 to 20 years after diagnosis with symptoms worsening over time. There is no known cure or therapy that alters the course of the disease.

The cause of Huntington's disease was discovered over three decades ago--a "genetic stutter" mutation involves repeats of three letters of the DNA, cytosine-adenine-guanine (CAG), in a gene called huntingtin. Healthy individuals usually have 35 or fewer CAG repeats, but people inherited with mutation of 40 or more repeats will develop the disease. The more CAG repeats a person inherits, the earlier the disease onset occurs. However, how the mutation causes the disease remains poorly understood. 

Opening for a new type of drug for Alzheimer’s Disease

Kaj Blennow and Tohidul Islam.
Photo Credit: Johan Wingborg

A complementary drug to combat Alzheimer’s disease could target a specific part of the nerve cell protein tau. This is the finding of research from the University of Gothenburg, which also offers a better way to measure the effect of treatment among patients.

Researchers from the University of Gothenburg, together with colleagues from the University of Pittsburgh in the US, published their findings in the journal Nature Medicine.

The study provides insights into what happens during the earliest phase when the protein tau is transformed into thread-like strands (fibrils) in the nerve cells. This is one of the processes in Alzheimer’s disease and occurs alongside the formation of amyloid plaques. In healthy individuals, the protein tau stabilizes the tubular building blocks (microtubules) that make up the long projections of the nerve cells.

During the development of Alzheimer’s disease, tau undergoes pathological changes. First, tau forms small, soluble aggregates that are secreted from the nerve cells and are thought to be able to spread these changes to other nerve cells. The protein is then converted into larger, harmful, thread-like strands in the nerve cells.

Research Pinpoints Weakness in Lung Cancer’s Defenses

A microscope image of lung cancer cells (purple) containing the activated form of a metabolic enzyme called GUK1 (brown) that supports cancer growth.
Image Credit: Haigis lab

Lung cancer is a particularly challenging form of cancer. It often strikes unexpectedly and aggressively with little warning, and it can shapeshift in unpredictable ways to evade treatment.

While researchers have gleaned important insights into the basic biology of lung cancer, some of the disease’s molecular maneuvers have remained elusive.

Now, a team led by scientists at Harvard Medical School has made strides in understanding how a genetic flaw in some lung cancers alters cancer cell metabolism to fuel the disease.

Working with mouse models and human cancer cells, the researchers identified a metabolic enzyme called GUK1 in lung cancers harboring an alteration in the ALK gene. Their experiments showed that GUK1 plays an important role in boosting metabolism in tumor cells to help them grow.

The findings, reported in Cell and supported in part by federal funding, provide a clearer picture of how metabolism works in lung cancer.

The research could set the stage for developing therapies that target GUK1 to curb cancer growth, the team said.

UCLA researchers find high levels of the industrial chemical BTMPS in fentanyl

Image Credit: Colin Davis

A UCLA research team has found that drugs being sold as fentanyl contain high amounts of the industrial chemical bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate, or BTMPS. This new substance of concern emerged in the illicit drug supply nearly simultaneously in multiple U.S. locations from coast-to-coast.

From June through October 2024, the team quantitatively tested samples of drugs sold as fentanyl that had high levels of the chemical, which belongs to a class of compounds called hindered amine light stabilizers and has a variety of applications including as a sealant, adhesive, and additive to plastics. 

The paper is published in the peer-reviewed journal JAMA.

“The emergence of BTMPS is much more sudden than previous changes in the illicit drug supply, and the geographic range where it was detected nearly simultaneously suggests it may be added at a high level in the supply chain,” said study lead Chelsea Shover, an assistant professor-in-residence at the David Geffen School of Medicine at UCLA. “This is concerning because BTMPS is not approved for human consumption, and animal studies have shown serious health effects such as cardiotoxicity and ocular damage, and sudden death at certain doses.” 

Women of Science: A Legacy of Achievement

Future generations to pursue their passions and break down barriers in the pursuit of knowledge.
Image Credit: Scientific Frontline stock image

Throughout history, women have made groundbreaking contributions to science, despite facing significant societal barriers and a lack of recognition. Their relentless pursuit of knowledge and innovation has shaped our understanding of the world and paved the way for future generations of scientists. This article celebrates the achievements of some of these remarkable women, highlighting their struggles and the impact of their work.

The women featured in this article, along with countless others throughout history, have made invaluable contributions to the advancement of science. Their achievements, often accomplished in the face of adversity and societal barriers, have shaped our understanding of the world and paved the way for future generations of scientists. These women demonstrate the power of perseverance, the importance of challenging established norms, and the profound impact that individual dedication can have on scientific progress. By recognizing and celebrating their legacies, we not only honor their contributions but also inspire future generations to pursue their passions and break down barriers in the pursuit of knowledge.

Mutations in two gene pairs point to a promising drug target in 5 percent of adult cancers

Illustration Credit: Natalie Velez, Broad Communications

Scientists from the Cancer Dependency Map (DepMap) at the Broad Institute of MIT and Harvard and Columbia University have discovered that about 5 percent of adult cancers rely heavily on a gene called PELO to survive and that disabling the gene kills those cancer cells. These cancers have mutations in one of two genes, FOCAD or TCC37.

The finding, described in Nature, is a new synthetic lethality — a pair of genetic changes that together kill cancer cells. The researchers say that PELO is a promising target, and that genetic testing could identify cancer patients with FOCAD or TCC37 mutations who would benefit from new PELO-targeting drugs.

“These cancers are a huge unmet medical need, because we don’t have effective drugs for them,” said Francisca Vazquez, co-senior author on the study along with postdoctoral researcher Edmond Chan, now an assistant professor at Columbia University. Vazquez is also director of DepMap, which systematically probes cancer cell lines for genetic vulnerabilities. 

“Targeting synthetic lethalities is a good way to expand the repertoire of tumors we’re able to treat,” Vazquez said. “This new synthetic lethality we found shows how powerful the DepMap datasets can be.”

Patricia Borck, a DepMap research scientist in Broad’s Cancer Program, is first author on the study.

Cutting edge technology shows promise in tackling deadly brain tumors

Delivering advanced gene-editing tools directly to the tumor site can improve the body’s defense against glioblastoma
Image Credit: Gemini

A new study led by Khuloud Al Jamal, Professor of Drug Delivery & Nanomedicine, has found an innovative strategy to combat glioblastoma (GB), a fast-growing and aggressive type of brain tumor.

GB is a brain tumor originating in the brain or spinal cord. Despite advances in cancer treatment, it can remain resistant to therapies, including immune checkpoint (ICP) blockade therapies. ICP blockade works by targeting specific proteins on immune or tumor cells to prevent tumors from evading the immune system. While effective in other cancers, this approach has shown limited success in treating GB. The is due to complex interactions between immune cells and glioblastoma stem cells (GSCs), which suppress the immune response and reduce the effectiveness of these therapies.

In the study, published in Advanced Science, Professor Al Jamal and her team revealed how they have taken a novel approach to overcome this challenge by focusing on the mesenchymal subtype of GSCs, which is particularly aggressive and therapy resistant. The study employed lipid nanoparticles (LNPs) — tiny, fat-based carriers — to transport CRISPR RNAs, an advanced gene-editing tool, to GSC and immune cells in therapeutically relevant tumor models. 

Spinal cord stimulation: A transformative option for chronic pain management

Image Credit: cottonbro studio

Chronic back and lower extremity pain are leading causes of disability worldwide, significantly impacting the quality of life and productivity of the patients affected by them. For these patients, spinal cord stimulation (SCS) — a non-pharmacological, neurostimulation treatment that involves the surgical implantation of electrodes and a power source to deliver electrical current to the spinal cord to reduce pain signals to the brain — offers an advanced, safe and minimally invasive treatment option.

SCS is not a new medical technology, but has evolved considerably since its introduction in the 1960s. “It was historically used for patients who had undergone spine surgery but continued to experience pain,” explains Jonathan Droessler, MD, a specialist in interventional physiatry at UCLA’s Department of Orthopedic Surgery.

“Today, it’s used for patients with intractable pain lasting more than six months.”

Omega-3s Can Slow Down Aging Process

In addition to the well-documented health benefits, a recent evaluation of the DO-HEALTH study indicates that the intake of omega-3 fatty acids can also slow down the ageing process.
Photo Credit: Polina Tankilevitch

A daily intake of one gram of omega-3s can slow down biological aging by up to four months, according to an analysis of clinical data from the international DO-HEALTH study led by the University of Zurich. For the first time, epigenetic clocks were used to measure the aging process.

Many people would like to delay or even stop the aging process. Previous clinical studies have shown that a reduced calorie intake can slow down the aging process in humans. Taking vitamin D or omega-3 fatty acids has also shown promising results in slowing biological aging in animals. However, it was unclear whether these measures would also work in humans.

The therapies previously tested in the DO-HEALTH study led by Heike Bischoff-Ferrari are also associated with a slowing of the aging process. These showed that vitamin D and omega-3 fatty acids, as well as regular physical activity, reduce the risk of infections and falls, and prevent cancer and premature frailty. “These results inspired us to measure the direct influence of these three therapies on the biological aging process in the Swiss DO-HEALTH participants,” says Bischoff-Ferrari, professor of geriatrics and geriatric medicine at the University of Zurich.

OHSU researchers identify protective properties of amniotic fluid

A multidisciplinary team of OHSU researchers collaborates to better understand the mechanism of amniotic fluid’s role in fetal development. Their goal is to identify how its properties can be harnessed to address prenatal health concerns.
Photo Credit: Christine Torres Hicks/OHSU

Researchers at Oregon Health & Science University have made new discoveries about amniotic fluid, a substance historically not well understood in medical research due to the difficulty in obtaining it during pregnancy, especially across gestation.

Amniotic fluid is the vital fluid that surrounds and protects a fetus during pregnancy. In addition to providing much-needed cushion and protection for the fetus, it also aids in development of vital organs — especially the lungs, digestive tract and skin— and stabilizes the temperature inside the womb.

The new study, published in the journal Research and Practice in Thrombosis and Haemostasis, found that the addition of amniotic fluid to plasma — the liquid portion of blood — improves the blood’s ability to thicken and clot, which is a critical and likely a protective function throughout pregnancy and during delivery for both the birthing parent and the baby.

The mechanism of amniotic fluid’s role in fetal development is not well understood and is understudied: The OHSU study is one of the first to identify how the features and properties of amniotic fluid change over time, especially those properties that play a role in thickening the blood, and how those changes can affect how maternal blood coagulates. If a pregnant person’s blood does not clot properly, it can create life-threatening complications for the fetus and birthing parent, including excessive bleeding during pregnancy and delivery.  

Powerful anticancer compound might also be the key to eradicating HIV

Study co-authors Jennifer Hamad and Owen McAteer prepare for a cellular assay, a lab technique used to study living cells. The assay will yield information about the location of EBC-46 compounds that have been introduced into cells in the lab.
Photo Credit: Paul Wender

A compound with the unpresuming designation of EBC-46 has made a splash in recent years for its cancer-fighting prowess. Now a new study led by Stanford researchers has revealed that EBC-46 also shows immense potential for eradicating human immunodeficiency virus (HIV) infections. 

Compared to similar-acting agents, EBC-46 excels at activating dormant cells where HIV is hiding, the study found. These “kicked” cells can then be targeted (“killed”) by immunotherapies to fully clear the insidious virus from the body. By pursuing this “kick and kill” strategy with EBC-46, researchers think achieving permanent elimination of HIV in patients—in other words, a cure—is possible.

"We’re pleased to report that EBC-46 performed extremely well in preclinical experiments as part of a ‘kick and kill’ therapeutic," said study senior author Paul Wender, the Bergstrom Professor of Chemistry at Stanford’s School of Humanities and Sciences. "While we still have a lot of work to do before treatments based on EBC-46 might reach the clinic, this study marks unprecedented progress toward the as-yet-unrealized goal of eradicating HIV.” 

OHSU researchers use AI machine learning to map hidden molecular interactions in bacteria

Andrew Emili, Ph.D., professor of systems biology and oncological sciences, works in his lab at OHSU. Emili is part of a multi-disciplinary research team that uncovered how small molecules within bacteria interact with proteins, revealing a network of molecular connections that could improve drug discovery and cancer research.
Photo Credit: OHSU/Christine Torres Hicks

A new study from Oregon Health & Science University has uncovered how small molecules within bacteria interact with proteins, revealing a network of molecular connections that could improve drug discovery and cancer research.

The work also highlights how methods and principles learned from bacterial model systems can be applied to human cells, providing insights into how diseases like cancer emerge and how they might be treated. The results are published today in the journal Cell.

The multi-disciplinary research team, led by Andrew Emili, Ph.D., professor of systems biology and oncological sciences in the OHSU School of Medicine and OHSU Knight Cancer Institute, alongside Dima Kozakov, Ph.D., professor at Stony Brook University, studied Escherichia coli, or E. coli, a simple model organism, to map how metabolites — small molecules essential for life — interact with key proteins such as enzymes and transcription factors. These interactions control important processes such as cell growth, division and gene expression, but how exactly they influence protein function is not always clear.

Child mortality has risen since pandemic, new study shows

Photo Credit: Josue Michel

While child deaths in England fell temporarily during the COVID-19 pandemic, they have now risen to new heights, a new study from researchers at the University of Bristol and based on unique National Child Mortality Database (NCMD) data has found.

The study, published in PLOS Medicine, has shown that children were less likely to die during the pandemic lockdown (April 2020–March 2021) than at any time before or since, with 377 fewer deaths than expected from the previous year.  

The number of deaths in the following year (2021-2022) was similar to before the pandemic, but in 2022−2023, there were 258 more deaths than expected from the pre-pandemic period. 

The aim of the research was to quantify the relative rate, and causes, of childhood deaths in England, before, during, and after national lockdowns for COVID-19 and its social changes.

The researchers identified all those children in England who died between April 2019 and March 2023 and calculated what the rate of death was for each year, for each group of children (e.g., infants or older children) and cause of death.

T cells rise up to fight infections in the gut

An image produced through Xenium analysis of mouse small intestines. Protruding “villi” stick up from the lining of the small intestine. Valley-like “crypts” fill in the gaps.
Image Credit: Reina Lab, La Jolla Institute for Immunology

Your gut is a battleground. The cells that line your small intestine have to balance two seemingly contradictory jobs: absorbing nutrients from food, while keeping a wary eye out for pathogens trying to invade your body.

“This is a surface where pathogens can sneak in,” says La Jolla Institute for Immunology (LJI) Assistant Professor Miguel Reina-Campos, Ph.D. “That’s a massive challenge for the immune system.”

So how do immune cells keep the gut safe? New research led by scientists at LJI, UC San Diego, and the Allen Institute for Immunology shows that pathogen-fighting immune cells called tissue-resident memory CD8 T cells (TRM cells) go through a surprising transformation—and relocation—as they fight infections in the small intestine.

In fact, these cells literally rise up higher in the tissue to fight infections before pathogens can spread to deeper, more vulnerable areas.

Study explains why some osteoporosis drugs may protect against Covid-19

Drugs already in-use for other conditions could help in the fight against Covid-19 and its variants
Photo Credit: Courtesy of University of York

Researchers have provided the molecular explanation for why some osteoporosis drugs offer protection against Covid-19.

Drugs already in-use for other conditions could help in the fight against Covid-19 and its variants

The study, by researchers at the University of York, builds on work conducted by Harvard Medical School that compared more than 450,000 users of a class of drugs, called bisphosphonates, with non-users during the months leading up to the pandemic in 2020. 

The Harvard study showed that those who used drugs, such as alendronate and zoledronate, had lower odds of testing for SARS-CoV-2 infection, Covid-19 diagnosis and Covid-19-related hospitalization, but the study didn’t explain why this was the case.

NIH-funded study finds cases of ME/CFS increase following SARS-CoV-2

Photo Credit: Bruno Aguirre

New findings from the National Institutes of Health’s (NIH) Researching COVID to Enhance Recovery (RECOVER) Initiative suggest that infection with SARS-CoV-2, the virus that causes COVID-19, may be associated with an increase in the number of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) cases. According to the results, 4.5% post-COVID-19 participants met ME/CFS diagnostic criteria, compared to 0.6% participants that had not been infected by SARS-CoV-2 virus.  RECOVER is NIH’s national program to understand, diagnose, prevent, and treat Long COVID.

The research team, led by Suzanne D. Vernon, Ph.D., from the Bateman Horne Center in Salt Lake City, examined adults participating in the RECOVER adult cohort study to see how many met the IOM clinical diagnostic criteria for ME/CFS at least six months after their infection. Included in the analysis were 11,785 participants who had been infected by SARS-CoV-2 and 1,439 participants who had not been infected by the virus. Findings appear in the Journal of General Internal Medicine.

Oxford researchers develop blood test to enable early detection of multiple cancers

Photo Credit: Fernando Zhiminaicela

Oxford University researchers have unveiled a new blood test, powered by machine learning, which shows real promise in detecting multiple types of cancer in their earliest stages, when the disease is hardest to detect.

Named TriOx, this innovative test analyses multiple features of DNA in the blood to identify subtle signs of cancer, which could offer a fast, sensitive and minimally invasive alternative to current detection methods.

The study, published in Nature Communications, showed that TriOx accurately detected cancer (including in its early stages) across six cancer types and reliably distinguished those people who had cancer from those that did not.

Cancers are more likely to be cured if they’re caught early, and early treatment is also much cheaper for healthcare systems. While the test is still in the development phase, it demonstrates the promise of blood-based early cancer detection, a technology that could revolutionize screening and diagnostic practices.

A team of researchers at the University of Oxford have developed a new liquid biopsy test capable of detecting six cancers at an early stage. The cancer types evaluated in this study were colorectal, esophageal, pancreatic, renal, ovarian and breast.

New study identifies how blood vessel dysfunction can worsen chronic disease

OHSU researchers have uncovered how specialized cells surrounding small blood vessels, known as perivascular cells, contribute to blood vessel dysfunction in chronic diseases such as cancer, diabetes and fibrosis. The findings could change how these diseases are treated.
Photo Credit: OHSU/Christine Torres Hicks

Researchers at Oregon Health & Science University have uncovered how specialized cells surrounding small blood vessels, known as perivascular cells, contribute to blood vessel dysfunction in chronic diseases such as cancer, diabetes and fibrosis. The findings, published in Science Advances, could change how these diseases are treated.

The study, led by Luiz Bertassoni, D.D.S., Ph.D., founding director of the Knight Cancer Precision Biofabrication Hub and a professor at the OHSU Knight Cancer Institute and the OHSU School of Dentistry, shows that perivascular cells sense changes in nearby tissues and send signals that disrupt blood vessel function, worsening disease progression.

Scientists engineer CRISPR enzymes that evade the immune system

Image Credit: Natalie Velez, Broad Communications

The core components of CRISPR-based genome-editing therapies are bacterial proteins called nucleases that can stimulate unwanted immune responses in people, increasing the chances of side effects and making these therapies potentially less effective. 

Researchers at the Broad Institute of MIT and Harvard and Cyrus Biotechnology have now engineered two CRISPR nucleases, Cas9 and Cas12, to mask them from the immune system. The team identified protein sequences on each nuclease that trigger the immune system and used computational modeling to design new versions that evade immune recognition. The engineered enzymes had similar gene-editing efficiency and reduced immune responses compared to standard nucleases in mice.

Appearing today in Nature Communications, the findings could help pave the way for safer, more efficient gene therapies. The study was led by Feng Zhang, a core institute member at the Broad and an Investigator at the McGovern Institute for Brain Research at MIT.

“As CRISPR therapies enter the clinic, there is a growing need to ensure that these tools are as safe as possible, and this work tackles one aspect of that challenge,” said Zhang, who is also a co-director of the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics, the James and Patricia Poitras Professor of Neuroscience, and a professor at MIT. He is an Investigator at the Howard Hughes Medical Institute.

Researchers discover how to mimic hibernation in non-hibernating animals

OHSU researcher Domenico Tupone, Ph.D., has discovered a method to control human body temperature, mimicking hibernation in non-hibernating animals. His research is focused on how controlled hypothermia may reduce tissue damage following a cardiac attack or stroke.
Photo Credit: OHSU/Christine Torres Hicks

In the same way a bear instinctively lowers its body temperature to survive the winter’s chill, scientists have discovered a groundbreaking method to control human body temperature —potentially saving lives in emergency situations.

Oregon Health & Science University researchers have identified a process that could one day help clinicians lower body temperature in people experiencing life-threatening events, such as heart attacks or strokes.

If applied in humans, who can’t naturally hibernate, the discovery could mimic the natural ability of certain animals to lower their body temperature during hibernation.

“The idea is to reduce the body temperature to a lower level so that tissues like the brain or heart don't need as much oxygen, allowing them to survive the ischemia [lack of oxygen to tissues] longer and improve the functional outcomes of strokes or heart attacks,” said Domenico Tupone, Ph.D., senior author of the study and research assistant professor of neurological surgery in the OHSU School of Medicine.