McMaster University: SFL Spotlight

McMaster University, located in Hamilton, Ontario, operates as a research-intensive academic institution structurally designed to bridge fundamental discovery, clinical translation, and commercialization. Relocating to Hamilton in 1930 and establishing its medical school in 1965, the institution pioneered problem-based learning and evidence-based medicine, prioritizing mathematically validated epidemiological data over traditional hierarchical medical authority.

Today, the research ecosystem integrates the principles of Indigenous data sovereignty, adhering to OCAP (ownership, control, access, and possession) principles through digital infrastructure initiatives like the Digital Research Commons Pilot. The administrative structure actively enforces equity, diversity, and inclusion mandates across clinical trial design and faculty onboarding. McMaster utilizes the Canada Research Chairs program to broaden its epistemological approaches, targeting representation goals for women, racialized individuals, persons with disabilities, and Indigenous peoples by 2029.

IMPDH2 Inhibitors: Blocking Metastatic Brain Cancer

Researchers Jakob Magolan (left) and Sheila Singh (right) have identified a new therapeutic approach to preventing metastatic brain cancer.
Photo Credit: Faculty of Health Sciences / McMaster University

Scientific Frontline: Extended "At a Glance" Summary: Selective IMPDH2 Inhibition in Metastatic Brain Cancer

The Core Concept: Researchers have developed novel, preventive therapeutics designed to intercept and destroy metastasizing cancer cells before they can form secondary tumors in the brain. This approach targets specific enzymatic mechanisms to block the neurological spread of primary lung, breast, skin, and other cancers.

Key Distinction/Mechanism: Previous oncological treatments targeted the general inosine monophosphate dehydrogenase (IMPDH) enzyme, which caused severe side effects by inhibiting healthy cellular function. This new approach selectively inhibits the IMPDH2 isoform; because IMPDH2 is vital for cancer cells initiating brain metastases but remains scarce in healthy tissue, the new compounds eliminate rogue cells without widespread toxicity.

Major Frameworks/Components:

• Isoform-Selective Inhibition: Targeting only the IMPDH2 enzyme variant to achieve a high degree of safety and selectivity over traditional pan-IMPDH inhibitors.
• Metastatic Interception: Shifting the treatment paradigm for metastatic brain cancer from palliative care to a preventive model that stops migrating cancer cells in transit.
• Pharmacokinetic Optimization: Designing and synthesizing compounds capable of maintaining effective half-lives, penetrating the blood-brain barrier, and functioning synergistically with existing oncological therapies.

Ancient Soil DNA Rewrites Mammoth Extinction Timeline

Anthropology PhD student Tyler Murchie is a lead author on research
about a new DNA recovery technique that pulls genomes of thousands
of ancient species from less than a gram of soil.
Photo by Emil Karpinski/McMaster University

Scientific Frontline: Extended "At a Glance" Summary: Ancient Environmental DNA

The Core Concept: Ancient environmental DNA (eDNA) recovery is the extraction and sequencing of microscopic genomic fragments preserved in permafrost, allowing scientists to reconstruct ancient ecosystems from a single gram of sediment.

Key Distinction/Mechanism: Instead of relying on intact bones or fossils, DNA capture-enrichment technology isolates genetic material directly from soil samples, providing a comprehensive genomic census of the plant and animal life that existed at a specific point in time.

Origin/History: In December 2021, a study published in Nature Communications analyzed a 30,000-year genomic record from the Klondike region of the Yukon, proving that woolly mammoths and North American horses survived into the mid-Holocene.

Major Frameworks/Components:

• Pleistocene-Holocene Transition: An era of extreme climatic instability 11,000 to 14,000 years ago, which triggered steep population declines in megafauna like mastodons and saber-toothed cats.
• Mid-Holocene Survival: Genomic data refutes the theory that human overhunting caused immediate extinction, showing that isolated populations persisted until roughly 5,000 years ago.
• Ecological Engineering: The loss of large grazing herbivores transformed the rich "Mammoth Steppe," previously an expansive grassland, into landscapes overrun by mosses and shrubs.
• Permafrost Archiving: The urgent collection and preservation of ancient genetic data before rising global temperatures thaw the Arctic permafrost.

Researchers find deadly fungus can multiply by having sex, which could produce more drug-resistant, virulent strains

 Jianping Xu, professor in McMaster University’s
Department of Biology and researcher with Canada’s
Global Nexus for Pandemics and Biological Threats
Credit: McMaster University

Researchers at McMaster University have unlocked an evolutionary mystery of a deadly pathogen responsible for fueling the superbug crisis: it can reproduce by having sex.

And while such fraternizing is infrequent, scientists report it could be producing more drug-resistant and more virulent strains of Candida auris, capable of spreading faster.

C. auris is a fungus that can cause severe infections and sometimes death, often striking immunocompromised hospital patients.

Unlike animals and plants, microorganisms of this nature usually divide and reproduce asexually, so one produces two, two produce four and so on, all genetically identical to each other, through a process of very simple division and without the exchange of genetic material.

“One of the really complex and puzzling questions about this fungal pathogen is its origin and how it reproduces in nature,” says Jianping Xu, a professor in McMaster’s Department of Biology and researcher with Canada’s Global Nexus for Pandemics and Biological Threats.

For the study, recently published online in Computation and Structural Biotechnology Journal, researchers analyzed nearly 1,300 strains available on a public database of C. auris genome sequences. They searched for and confirmed recombination events, or sexual activity.

The findings will help to further research because scientists can now replicate those sexual behaviors in the lab.

“The research tells us that this fungus has been recombined in the past and can recombine in nature, which enables it to generate new genetic variants rather quickly,” explains Xu. “That may sound frightening, but it’s a double-edged sword. Because we learned they could recombine in nature, we could possibly replicate the process in the lab, which could allow us to understand the genetic controls of virulence and drug resistance and potentially other traits that make it such a dangerous pathogen, much faster.”

The Skin Microbiome: A New Antimicrobial Source

McMaster University researcher Lindsay Kalan (right) and MSc student Jordana Ferro examine a dish containing skin-associated bacteria.
Photo Credit: Courtesy of McMaster University

Scientific Frontline: Extended "At a Glance" Summary: The Skin Microbiome as an Antimicrobial Reservoir

The Core Concept: The human skin microbiome constitutes a vast, diverse community of bacteria, fungi, and viruses that acts as a protective barrier against external pathogens. Recent research indicates that these endogenous microbial populations naturally produce novel antimicrobial compounds to defend their host.

Key Distinction/Mechanism: Unlike traditional antibiotic discovery, which typically relies on isolating microbes from environmental soil samples, this framework investigates the human body's native flora. Certain newly discovered skin-associated bacterial species act as "fungal specialists," synthesizing previously uncharacterized chemical molecules to directly inhibit drug-resistant pathogens.

Major Frameworks/Components:

• Epithelial Isolate Collection (EPIC): A comprehensive microbial library gathered from eight distinct microenvironments on the human body, representing an estimated 95 percent of the entire human skin microbiome.
• Biosynthetic Gene Clusters: Genetic sequences responsible for producing antimicrobial chemicals. Analysis revealed that 96 percent of the identified clusters in these specific skin microbes remain uncharacterized, suggesting immense potential for novel molecular discovery.
• Fungal Specialists: Three of the newly discovered bacterial species demonstrate a highly effective ability to deter severe, drug-resistant fungal pathogens, including Candida auris and species within the Cryptococcus genus.
• Broad-Spectrum Defense: Validation experiments confirmed that these skin microbes possess chemical defenses active against over 20 human pathogens, including Escherichia coli and Staphylococcus aureus.

Metabolic Cause of Statin Muscle Pain Discovered

Photo Credit: David Levinson

Scientific Frontline: Extended "At a Glance" Summary: Statin-Induced Muscle Myopathy Mechanism

The Core Concept: Researchers at McMaster University have identified the specific immune and metabolic pathway responsible for the muscle pain and weakness frequently caused by statin medications, offering a route to mitigate these side effects without compromising the drugs' cardiovascular benefits.

Key Distinction/Mechanism: While statins effectively lower cholesterol, they simultaneously disrupt cellular energy production within muscle tissue. This metabolic disruption triggers an inflammatory immune response directly within the muscle cells, causing structural damage. Crucially, this immune-metabolic mechanism operates entirely independently from the biochemical pathway that lowers cholesterol.

Major Frameworks/Components:

• Metabolic Disruption: Statins interfere with the standard energy production cycles of muscle cells.
• Autoimmune Inflammatory Response: The altered metabolism within the cell triggers a localized immune response, establishing a direct link between cellular metabolism and intracellular immunity.
• Targeted Immune Blockade: Experimental models in mice and isolated muscle cells demonstrated that suppressing this specific immune response prevents subsequent muscle damage.

Adolescent Signs of Chronic Pelvic Pain

Chronic pelvic pain is a debilitating condition that can affect up to one in four women and gender diverse people. A new McMaster University study has found that early warning signs may appear in adolescence.
Image Credit: Scientific Frontline / stock image

Scientific Frontline: Extended "At a Glance" Summary: Chronic Pelvic Pain in Adolescence

The Core Concept: Chronic pelvic pain (CPP) is a debilitating condition involving ongoing pain in the lower abdomen or pelvis lasting for months or years, the early warning signs of which frequently manifest during adolescence.

Key Distinction/Mechanism: Rather than emerging spontaneously in adulthood, vulnerability to CPP is often foreshadowed years prior by adolescent reproductive health complaints, alongside related gastrointestinal problems, mental health conditions, and other chronic pain patterns.

Major Frameworks/Components:

• Longitudinal population tracking to identify early risk factors from adolescence into adulthood.
• Early gynecologic and reproductive health care encounters as primary predictive indicators.
• Comorbid symptom assessment, including associated gastrointestinal and mental health conditions.
• Integrated care modeling to recognize systemic vulnerabilities before chronic pain becomes established.

Phage Protein Disarms Bacteria

McMaster researcher Lori Burrows (left) and postdoc Nathan Roberge (right) have discovered the broad antibacterial effects of a phage-based protein.
Photo Credit: Courtesy of McMaster University

Scientific Frontline: Extended "At a Glance" Summary: Phage Protein Aqs1 and Bacterial Disarmament

The Core Concept: Researchers have discovered that Aqs1, a specialized protein produced by bacteriophages, can broadly disable the infectious capabilities of multiple disease-causing bacteria by shutting down their structural machinery.

Key Distinction/Mechanism: While the specific phage that produces Aqs1 naturally infects only Pseudomonas aeruginosa, the protein itself targets a conserved molecular region shared across many pathogenic species. Aqs1 jams the engine responsible for producing type IV pili, preventing the bacteria from moving, adhering to host tissues, and receiving subsequent viral infections.

Major Frameworks/Components:

• Bacteriophages: Viruses that exclusively infect and replicate within specific bacterial hosts.
• Aqs1 Protein: The viral protein expressed during infection that suppresses bacterial pili production.
• Type IV Pili: Fibrous, hair-like appendages on the bacterial surface essential for motility, adhesion, and pathogenesis.
• Pseudomonas aeruginosa: A multidrug-resistant pathogen that serves as the natural host for the Aqs1-producing phage.

Viral Infections Accelerate ALS Progression

From left to right: Master’s student Imran Ahmed, Professor Matthew Miller, and postdoctoral fellow Art Marzok examining the photographic results of their study.
Photo Credit: Courtesy of McMaster University

Scientific Frontline: Extended "At a Glance" Summary: Viral Infections and ALS Progression

The Core Concept: Common respiratory viral infections, such as influenza A and SARS-CoV-2, can hasten the onset and accelerate the progression of amyotrophic lateral sclerosis.

Key Distinction/Mechanism: The acceleration is driven not by direct viral infection of neurons, but by gliosis, an inflammatory immune response in the nervous system that elevates scar tissue in the spinal cord long after the virus clears.

Major Frameworks/Components:

• Animal models infected with influenza A and SARS-CoV-2 to monitor motor function decline.
• Mechanistic analysis of gliosis and inflammatory immune cell responses in the nervous system.
• Pre-clinical therapeutic intervention using antivirals and anti-inflammatories to reduce the rate of disease progression.

2025 Marburg Outbreak: Genomic Tracking in Ethiopia

Marburg virus, captured with the specific appearance of a colorized Transmission Electron Micrograph (TEM)
Image Credit: Scientific Frontline / AI generated

Scientific Frontline: Extended "At a Glance" Summary: The 2025 Ethiopian Marburg Virus Outbreak

The Core Concept: The 2025 Marburg virus outbreak in Ethiopia, a highly fatal viral hemorrhagic fever, was traced to a single zoonotic spillover event from animals to humans through rapid genomic analysis.

Key Distinction/Mechanism: Unlike outbreaks characterized by multiple independent animal-to-human transmission events, genetic sequencing of the virus revealed remarkably little variation between patient samples, proving the outbreak descended from a shared ancestral virus via a single chain of transmission.

Origin/History: The outbreak emerged in Ethiopia in November 2025, infecting 14 individuals and yielding a 64 percent case fatality rate, with the suspected patient zero having worked at a construction site colonized by Egyptian fruit bats (Rousettus aegyptiacus).

Major Frameworks/Components:

• Genomic-based surveillance to identify and map the viral genome.
• Rapid diagnostic sequencing workflows used to confirm the causative agent within 48 hours.
• Epidemiological contact tracing to track the localized, human-to-human transmission chain.
• Zoonotic pathogen transmission modeling from a known animal reservoir to human populations.

Ultra-Processed Foods and Silent Strokes

Photo Credit: Nico Smit

Scientific Frontline: Extended "At a Glance" Summary: Ultra-Processed Foods and Cerebrovascular Damage

The Core Concept: High consumption of ultra-processed foods by healthy middle-aged adults is directly associated with asymptomatic cerebrovascular damage, serving as an early warning sign for clinical stroke and future cognitive decline.

Key Distinction/Mechanism: Unlike acute cardiovascular events, this damage presents as microscopic "silent strokes" detectable only via magnetic resonance imaging (MRI). The neuropathology strongly correlates with increased abdominal adiposity, which initiates systemic inflammation and subsequent cerebral blood vessel degradation.

Major Frameworks/Components:

• Utilization of MRI technology to detect localized, asymptomatic brain lesions in a cohort of nearly 9,000 individuals aged 35 to 69 with no prior history of heart disease.
• Classification of dietary intake based on industrial processing levels, emphasizing diets high in sodium, added sugars, and saturated fats, while lacking essential vitamins and fiber.
• Identification of dietary displacement, demonstrating that high volumes of ultra-processed foods actively crowd out nutrient-dense, minimally processed whole foods rather than simply adding caloric surplus.
• Observation of a pronounced sex-based disparity, where women in the highest consumption quartile exhibited nearly double the risk of brain damage compared to those in the lowest consumption group.

EndoFusion: AI Speeds Up Endometriosis Diagnosis

Photo Credit: Courtesy of Adelaide University

Scientific Frontline: Extended "At a Glance" Summary: EndoFusion

The Core Concept: EndoFusion is an artificial intelligence diagnostic tool that rapidly and noninvasively detects signs of advanced endometriosis from a single pelvic scan.

Key Distinction/Mechanism: Unlike the current standard of visual identification through invasive, costly, and slow keyhole surgery, EndoFusion utilizes machine learning to integrate and analyze data from both magnetic resonance imaging (MRI) and transvaginal ultrasound scans. This circumvents the limitations of relying on single imaging methods and the variabilities of operator experience.

Major Frameworks/Components:

• Diagnostic Datasets: The system was trained using information gathered from four datasets, comprising more than 9,000 female pelvic MRI scans and over 800 transvaginal ultrasound sliding scans.
• Algorithmic Efficacy: The framework achieves an 83% accuracy rate in distinguishing between positive and negative cases of endometriosis, outperforming all competing models, and produces results in just 18 milliseconds.
• Interdisciplinary Collaboration: The ongoing development includes partnerships with Flinders University, Benson Radiology, Omni Ultrasound and Gynecological Care, the University of Surrey, the McMaster University Medical Center, and the Mohamed bin Zayed University of Artificial Intelligence.

Two-dimensional oxides open door for high-speed electronics

Furkan Turker, graduate student in the Department of Materials Sciences, works on a silicon carbide chip in the laboratory 
Photo Credit: Pennsylvania State University
 Creative Commons

Advances in computing power over the decades have come thanks in part to our ability to make smaller and smaller transistors, a building block of electronic devices, but we are nearing the limit of the silicon materials typically used. A new technique for creating 2D oxide materials may pave the way for future high-speed electronics, according to an international team of scientists.

“One way we can make our transistors, our electronic devices, work faster is to shrink the distance electrons have to travel between point A and B,” said Joshua Robinson, professor of materials science and engineering at Penn State. “You can only go so far with 3D materials like silicon — once you shrink it down to a nanometer, its properties change. So, there’s been a massive push looking at new materials, one of which are 2D materials.”

The team, led by Furkan Turker, graduate student in the Department of Materials Sciences, used a technique called confinement hetroepitaxy, or CHet, to create 2D oxides, materials with special properties that can serve as an atomically thin insulating layer between layers of electrically conducting materials.

“Now we can create essentially the world’s thinnest oxides — just a few atoms thick,” Turker said. “That allows you to bring conducting layers closer together than ever without letting them touch. This enables the formation of an ultrathin barrier between conducting layers, which is essential for the fabrication of next-generation electronic devices, such as diodes or transistors.”

Single drug injection wards off COVID-19 hospitalizations

A single injection of PEG-lambda interferon proved to be effective against all variants of the coronavirus tested by researchers at Stanford Medicine.
Image Credit: Gerd Altmann

In an international, multicenter, pivotal Phase 3 trial, a single under-the-skin injection of a biological drug given to patients within seven days of the onset of COVID-19 symptoms cut the likelihood they needed to be hospitalized in half. Patients treated within three days of showing symptoms fared even better. Among unvaccinated patients who were treated soon after symptom onset, hospitalization likelihood plummeted markedly.

The drug, pegylated lambda-interferon, or PEG-lambda, proved effective against all COVID-19 viral variants tested, including omicron. Side effects were no greater than those reported by placebo recipients.

A report on the success of the randomized, double-blind, placebo-controlled trial of nearly 2,000 newly infected COVID-19 patients was published online Feb. 9 in the New England Journal of Medicine.

PEG-lambda is a synthetic version of lambda-interferon, a naturally occurring protein that infected cells secrete as a first line of defense against viral infection.

Staying on long-term antidepressants reduces risk of relapse

 

When people stop taking antidepressants after a long period of use, just over half (56 per cent) experience a relapse within a year, compared to 39 per cent of those who stay on medication, finds a new study led by UCL and involving researchers from the universities of Bristol, Southampton, York and McMaster University in Canada.

The researchers say their findings, published in The New England Journal of Medicine, can help doctors and patients to make an informed decision together on whether or not to stop their antidepressants after recovery from a depressive episode.

The study is the first publication from a large discontinuation trial of people taking antidepressants for multiple years in primary care.

Lead author Dr Gemma Lewis (UCL Psychiatry) said: “Prescriptions of antidepressants have increased dramatically over recent decades as people are now staying on antidepressants for much longer. Until now we didn’t know whether antidepressant treatment was still effective when someone has been taking them for many years.

“We have found that remaining on antidepressants long-term does effectively reduce the risk of relapse. However, many people can stop their medication without relapsing, though at present we cannot identify who those people are.”

Prefrontal Brain Activity and Behavior

Image Credit: Courtesy of University of Nottingham

Scientific Frontline: Extended "At a Glance" Summary: Prefrontal Brain Activity and Behavioral Flexibility

The Core Concept: A new study demonstrates how both suppressed neural activity (hypofrontality) and excessive neural activity (disinhibition) in the prefrontal cortex disrupt the brain's ability to adapt behaviors to changing circumstances.

Key Distinction/Mechanism: Hypofrontality impairs the ability to adapt during the early stages of reversal learning when rules first change, whereas prefrontal disinhibition (caused by reduced GABA-mediated inhibition) impairs performance during later stages when subjects are otherwise proficient at adapting.

Origin/History: Published in the Journal of Neuroscience by researchers from the University of Nottingham and Boehringer Ingelheim Pharma GmbH, the study utilized animal models to investigate cognitive impairments commonly associated with conditions like schizophrenia.

Major Frameworks/Components:

• Hypofrontality: Abnormally low activity in the prefrontal cortex.
• Prefrontal Disinhibition: Excessive prefrontal neural activity resulting from a weakened GABAergic braking system.
• Reversal Learning: A cognitive testing paradigm requiring subjects to abandon a previously learned, correct strategy for a newly correct one.
• Chemogenetics: An adapted technology utilized by the researchers to selectively manipulate GABA-releasing inhibitory neurons within specific brain regions.