Findings

Dr. Kirk Deitsch, professor of microbiology and immunology, senior author of a study that showed how a parasite that causes malaria when transmitted through a mosquito bite can hide from the body’s immune system, sometimes for years.

It turns out that the parasite, Plasmodium falciparum, can shut down a key set of genes, rendering itself “immunologically invisible.”

The preclinical results, published in Nature Microbiology, reveal that in regions where malaria is endemic, asymptomatic adults likely harbor undetectable parasites that mosquitos may pick up and transfer to the next person they bite.

Addictive Screen Use Puts Youth at Risk

New research could signal a paradigm shift in how the impact of screen time on youth mental health is addressed. Unlike previous studies that focused on total screen time at one point in a child’s life, this one looked at how young people’s patterns of compulsive or “addictive” use changed over time. These patterns included feeling unable to stop using a device, experiencing distress when not using it or using it to escape from problems.

Scientists found that youth who become increasingly addicted to social media, mobile phones or video games are at greater risk of suicidal thoughts, suicide attempts and emotional or behavioral issues.

“For parents and educators, the discussion around mobile phones and social media has focused on limiting or banning use, but our results indicate more complex factors are involved,” says first author Dr. Yunyu Xiao, assistant professor of population health sciences.

The researchers’ takeaway? “Testing interventions that work against other types of addiction may be one way to approach this type of social media and mobile phone use,” says Dr. Xiao, whose team collaborated with researchers at Columbia University and University of California, Berkeley, for their study, which appeared in JAMA.

More Accurate Sorting of Cancer Patients

 A new artificial intelligence-based method accurately sorts cancer patients into groups that have similar characteristics before treatment and similar outcomes after treatment. The approach has the potential to enable better patient selection in clinical trials and better treatment selection for individual patients.

The study, published in Nature Communications, was a collaboration with Regeneron Pharmaceuticals, and addressed how to predict which patients will have the best responses to a drug. The results showed that the new method’s ability to predict treatment outcomes from health record data was better than that of any other method published to date.

“We’re hopeful that this approach ultimately will be useful for testing and targeting treatments across a wide range of diseases,” says senior author Dr. Fei Wang, founding director of the Institute of AI for Digital Health in the Department of Population Health Sciences and associate dean of artificial intelligence and data science.

Dr. Benjamin Hopkins, senior author of a preclinical study published in Cell Reports Medicine, which showed that a pairing of two experimental drugs inhibits tumor growth and blocks drug-induced resistance in ovarian cancer.

The research reveals a promising strategy against this hard-to-treat malignancy, and more generally demonstrates a powerful new approach for the identification of effective regimens to treat genetically diverse cancers.

Ovarian cancer is genetically diverse in the sense that it can be driven by mutations in many different genes. This complicates the standard strategy of developing drugs to target common driver mutations. In the study, the researchers applied a new precision medicine approach focused not on individual mutations but instead on the activation of growth signaling pathways specific to ovarian tumor cells. Using this pathway-level data, they identified a new combination treatment strategy that selectively targets ovarian tumor cells and reduces ovarian tumor growth in preclinical models.

Dr. Hopkins, an assistant professor of research in systems and computational biomedicine and a member of the Englander Institute for Precision Medicine and the Sandra and Edward Meyer Cancer Center, hopes that these results will spur drug developers’ interest in this approach.

Intervening Earlier in Breast Cancer

A large prospective, randomized clinical trial in patients with advanced breast cancer has found that the use of liquid biopsy blood tests for early detection of a treatment-resistance mutation, followed by a switch to a new type of treatment, substantially extends the period of tumor control compared to standard care.

“The main message here is that liquid biopsy technology allows us to intervene sooner when the tumor burden is lower and the chance of a good outcome is higher,” says study co-author Dr. Massimo Cristofanilli, professor of medicine at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center, of the SERENA-6 study, which appeared in The New England Journal of Medicine.

Tiny Tag, Big Implications

A tiny chemical modification commonly found on messenger RNAs plays a surprisingly large role in how cells respond to stress. The finding clarifies an important aspect of cell biology and may have clinical implications, since this messenger RNA modification, known as m6A, is the target of an emerging class of cancer treatments.

Messenger RNA (mRNA) — the molecule that carries genetic instructions to make proteins — is often marked with m6A, a chemical modification that acts like a “disposal tag.” Cell survival and other stress response messenger RNAs often contain many more m6As than average messenger RNAs. Under normal conditions, this tag helps break down these messenger RNAs, keeping stress response proteins at low levels.

In the study, published in Cell, the researchers uncovered surprising details of how this all works. They discovered that m6A triggers mRNA disposal while the mRNA is being read by the ribosome, the cellular machine that converts the instructions in mRNA into specific proteins. They found that the ribosome does more than just read the mRNA — it searches for m6A on the molecule and ensures that mRNAs with the modification are targeted for degradation. The scientists then found that this disposal process was put on hold when the cell is stressed — allowing stress response messenger RNAs to accumulate and produce proteins that help the cell recover.

“These findings answer fundamental questions about m6A, in ways that are going to shift how we think about its roles in cell stress responses and cancers,” says study senior author Dr. Samie Jaffrey, the Greenberg-Starr Professor in the Department of Pharmacology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

Illustrations: Grace Russell