image: A MSK researcher at work.
Credit: Memorial Sloan Kettering Cancer Center
New research from Memorial Sloan Kettering Cancer Center (MSK) investigates how a natural antifungal compound produced by helpful gut bacteria might help protect vulnerable patients; finds that a protein “fingerprint” in blood could predict dangerous clots in cancer patients; uncovers Americans’ changing relationship with dietary supplements; and reveals how NK cells respond to infections so quickly.
Natural antifungal compound produced by helpful gut bacteria might protect vulnerable patients from deadly infections
Numerous fungal species quietly inhabit the intestines of healthy people without causing harm. But in patients undergoing bone marrow transplants or other intensive treatments that disrupt the microbiome, these fungi can expand rapidly and cause serious infections.
A new study from the labs of MSK physician-scientist Tobias Hohl, MD, PhD, and MSK computational biologist Joao Xavier, PhD, sheds light on how bacteria in the gut normally keep these fungi in check and points toward a potential new strategy to protect vulnerable patients. The work was led by Keiko Yasuma-Mitobe, MD, PhD, a research fellow in the Hohl Lab.
The study focused on cross-species interactions between bacteria and fungi that shape the microbial balance in the gastrointestinal tract. Using a machine learning approach, the team screened the secreted metabolites of hundreds of helpful (commensal) bacterial species to identify molecules capable of suppressing the growth of a common fungus called Candida parapsilosis. The analysis pinpointed valeric acid — a short-chain fatty acid produced by various gut bacteria — as a potent inhibitor of fungal growth. The team validated their findings in fecal samples from patients who had undergone bone marrow transplantation at MSK, finding that reduced levels of valeric acid were closely associated with higher levels of C. parapsilosis.
Further laboratory experiments revealed the underlying mechanisms: Valeric acid disrupts the internal pH balance of fungal cells, impairing their ability to grow. Notably, valeric acid was found to be more potent than other related compounds and worked against multiple Candida species, including C. albicans and C. auris, an emerging drug-resistant fungal pathogen.
When the researchers gave encapsulated valeric acid to mice colonized with Candida, it reduced fungal growth in the gut — a promising sign that the approach might help protect patients from fungal infections.
“These findings provide a proof-of-concept for using bacterial metabolites to reduce fungal overgrowth in the gut — a fairly simple idea, but one that could help protect our most vulnerable patients from life-threatening infections,” says Dr. Hohl, who also heads the Infectious Diseases and Allergy Service at MSK.
Read more in Cell Host & Microbe.
Protein “fingerprint” in blood could predict dangerous clots in cancer patients
Blood clots are a serious and common complication in cancer patients, but doctors have had limited tools to predict who is most at risk or understand why they occur. In a new multinational study, MSK Hematology Service Chief Jeffrey Zwicker, MD, and colleagues analyzed more than 1,000 proteins in blood samples from cancer patients and used machine learning to identify a panel of 11 proteins that can predict which patients would later develop dangerous blood clots, far outperforming the current standard prediction tool. Co-senior authors on the study include Ioannis Vlachos, PhD, of the Harvard University–affiliated Beth Isreal Deaconess Medical Center and the Broad Institute, and Sol Schulman, MD, PhD, of Beth Isreal Deaconess Medical Center.
Digging deeper into one of those proteins led the team to an unexpected discovery: An inflammatory pathway driven by a molecule called interleukin-17A (IL-17A) appears to play a key role in promoting clot formation. FDA-approved antibodies that block IL-17A are already used to treat autoimmune conditions like psoriasis but have never been studied for blood clot prevention. A meta-analysis in COVID-19 patients treated with these antibodies showed an 83% reduction in clot risk, suggesting significant therapeutic promise.
Read more in Science Translational Medicine.
More Americans are taking dietary supplements — and what they take is changing
Many adults in the United States report taking dietary supplements such as vitamins, minerals, botanicals, and probiotics, as well as products that claim to provide specific health benefits. A new study from researchers at MSK looked at 25 years of data to understand how the use of dietary supplements has changed over time. They analyzed information from more than 63,000 adults collected between 1999 and 2023 as part of a large, ongoing national health survey.
The research was led by postdoctoral fellow Chun Sing “Jason” Lam, PhD, who is a member of the lab of Jun Mao, MD, MSCE, in the Integrative Medicine and Wellness Service at MSK. The study’s senior author is Elizabeth Kantor, PhD, MPH, from MSK’s Department of Epidemiology and Biostatistics.
The researchers found that the percentage of American adults taking dietary supplements increased significantly — from about 51% in 1999 to 60% in 2023 — with most of this growth occurring in 2010 or later. The increase was particularly pronounced among older adults, whose usage rates rose from 62% to 78% over the study period.
Notably, the types of supplements that people take have changed. Traditional multivitamins have become less popular. Instead, people are reaching for more specialized supplements, including vitamins and minerals taken separately (like vitamin D, zinc, and magnesium) and formulated products for relieving joint pain, improving gut health, or combatting inflammation. There also has been a surge in supplements that claim to boost the immune system, particularly since the start of the COVID-19 pandemic.
“This type of epidemiologic research is important, because it helps us learn more about how supplement use is changing over time and which products people are actually taking,” Dr. Lam says. “While some of these supplements have solid research behind them, many others do not. It’s important that people discuss supplement use with a healthcare provider, because these products may have negative interactions with medications.”
Read more in JAMA Network Open.
How do NK cells respond to infections so quickly? MSK research uncovers the molecular mechanisms
Natural killer (NK) cells are a critical part of the body’s immune defenses, springing into action to kill invaders within minutes of detecting an infection, but exactly how they manage to respond so quickly hasn’t been clear. A new study from the lab of immunologist Joseph Sun, PhD, at MSK’s Sloan Kettering Institute sheds light on the molecular mechanisms behind this rapid response — which is critical given how fast many pathogens can replicate.
The research — led by Hyunu Kim, a graduate student at the Gerstner Sloan Kettering Graduate School of Biomedical Sciences — reveals that within minutes of NK cells encountering early inflammatory signals, a protein called RNA polymerase II (Pol II) rapidly repositions itself along the NK cell’s DNA. RNA Polymerase II is a cellular “scribe” that transcribes genomic information into messenger RNA for protein production, and by rapidly shifting its position along the NK cell’s DNA, it readies the cell to activate infection-fighting proteins almost immediately.
The team found that this repositioning is orchestrated by a protein called STAT4, which acts as a master regulator of the response to specific inflammatory signals like the cytokine interleukin-12 (IL-12). They also identified a previously unknown partner protein, DDX5, that works alongside STAT4 to fine-tune the process and enable NK cells to produce optimal amounts of interferon-gamma (IFN-γ) — a key molecule for fighting infections.
The insights could open new doors for treating diseases in which the immune system is overactive — as is the case in autoimmune conditions — or when it’s too weak, the researchers say.
Read more in the Journal of Experimental Medicine.