image: An MSK researcher in the lab.
Credit: Memorial Sloan Kettering Cancer Center
New research from Memorial Sloan Kettering Cancer Center (MSK) develops a powerful new resource for studying gene regulation across eukaryotes; uncovers how “jumping genes” can drive cancer growth; describes how an unexpected oxygen sensor regulates ferroptosis; establishes a technique to map chromatin architecture in 3D; creates new models for studying schizophrenia-associated defects; and finds transcription factor 19 is critical for the responses of natural killer cells to viral infection.
A powerful new resource for studying gene regulation across eukaryotes
An international research team led by scientists at MSK and the University of Toronto has developed a new platform to facilitate the study of RNA-binding proteins (RBPs) across hundreds of species of plants, insects, and animals.
These proteins are essential for controlling how genes are turned off and on — influencing cellular functions and protein production, making them critical for understanding health and disease.
“Yet, despite their importance, we haven’t fully understood which RNA sequences these proteins bind to or how they do it,” says computational biologist Quaid Morris, PhD, who jointly oversaw the project with Timothy Hughes, PhD, from the University of Toronto. “Currently, less than 0.1% of all eukaryotic RBPs have any available RNA binding data, most of which are from mammals or fruit flies.”
The new, freely available resource, EuPRI (for Eukaryotic Protein-RNA Interactions), marks a significant expansion of our knowledge of these interactions. It offers a detailed map of RNA sequences, called motifs, for nearly 35,000 RBPs across nearly 700 species.
For example, it increases the number of known RBP motifs for Arabidopsis thaliana (a plant in the mustard family) seven-fold, from 14 to 105.
Further, the platform uses a cutting-edge computational method called Joint Protein-Ligand Embedding (JPLE) to predict the binding preferences of previously unknown RBPs by learning the patterns and rules of how proteins recognize and latch on to specific RNA sequences.
“By doing so, it provides insights into evolutionary history, highlighting how RNA-protein interactions have quickly adapted in certain groups, like worms and plants,” Dr. Morris adds. “And, on a more applied level, it will allow scientists to predict how changes or mutations in RNA or these proteins might influence different diseases and thus help to develop new therapies.” Read more in Nature Biotechnology.
MSK researchers discover how ‘jumping genes’ can drive cancer growth
A recent study led by MSK investigators has revealed how some healthy cells can become cancerous. Our DNA contains transposable elements, known as jumping genes, that move from one part of the genome to another. Unlike most genes that stay in one place, these genes can “jump” to new locations, acting as a switch that turns nearby genes on or off. In healthy cells, this is a tightly regulated system of checks and balances. But when this system breaks down, jumping genes can mistakenly activate genes that drive uncontrolled cell growth, which can lead to cancer.
Elissa Wai Pung Wong, PhD, Merve Sahin, PhD, Christina Leslie, PhD, Ping Chi, MD, PhD, and their collaborators studied how this process can contribute to melanoma. Nipped-B-like protein is one of many that fold DNA into 3D structures called chromosomes. These structures are dynamic and can expose or hide parts of DNA, determining which genes are switched on and off. The researchers observed that when cells produce too little nipped-B-like protein, chromosome structures weakened, exposing previously hidden genes. This change allows transposable elements to recruit nearby enhancers, which are segments of DNA that boost gene activity, and activate genes that promote cancer growth. The study sheds light on how disruptions in chromosome structure can promote cancer-driving genes, offering new clues for future therapies. Read more in Nature Genetics.
Unexpected oxygen sensor regulates ferroptosis
Ferroptosis is an iron-dependent cell death process that is important in various diseases, including cancer. While metabolic ingredients such as glucose, lipids, and various amino acids have been demonstrated to modulate ferroptosis, the role of oxygen in ferroptosis is not fully understood.
Now MSK researchers — led by co-first authors Alexander Minikes, PhD and Pei Liu, PhD in the lab of senior author Xuejun Jiang, PhD, at the Sloan Kettering Institute — have shown that cells that are acclimated to a prolonged low-oxygen environment develop significant resistance to ferroptosis, and this resistance is independent of a well-established oxygen-sensing pathway mediated by the master transcription regulator of hypoxia, HIF.
Instead, they found low oxygen suppresses ferroptosis by inhibiting KDM6A — a tumor suppressor and oxygen-dependent histone demethylase, which, through transcriptional regulation, rewires the cellular lipidome toward a ferroptosis-resistant status. Relevant to cancer therapy, blocking EZH2, a cancer-promoting enzyme that counteracts KDM6A activity, restored the vulnerability of tumors to ferroptosis in mice transplanted with bladder cancer tissue harboring KDM6A mutations. Read more in Molecular Cell.
Technique developed at MSK maps chromatin architecture in 3D
Chromatin — the material that makes up chromosomes — is crucial for controlling genome expression, maintaining the integrity of our genes and ensuring accurate DNA replication.
To delve deeply into chromatin organization, the MSK researchers — led by first author Axel Delamarre, PhD, a senior research scientist in the lab of senior author Iestyn Whitehouse, PhD — developed an innovative method called Proximity Copy Paste (PCP). This technique allowed the team to map how molecules interact in three-dimensional space within cells, particularly focusing on nucleosomes, which are structural units of chromatin.
Applying the technique to yeast cells allowed the researchers to see that chromatin primarily consists of regularly spaced arrays of nucleosomes, which can be tightly organized or spread out. They further showed that during cell division, chromosomes get condensed due to clusters of loop structures created by a protein called cohesin. Additionally, the team found that overlapping pairs of nucleosomes, which are not commonly recognized, are actually a stable aspect of chromatin architecture.
“Our study showed that PCP can be used to map chromatin with high resolution while also capturing interactions that happen over larger distances within the 3D space of the cell nucleus,” Dr. Whitehouse says. “The approach should pave the way for a more holistic understanding of many chromatin interactions that occur in cells.” Read more in Molecular Cell.
New brain models for studying schizophrenia-associated defects
A team led physician-scientist Lorenz Studer, MD, has created 3D brain models to shed light on the development of specific kinds of brain cells called fast-spiking human PVALB+ cortical interneurons. These cells, which can fire rapidly and repeatedly in response to stimuli, are often disrupted in disorders such as schizophrenia. The brain model allowed the researchers to identify defects at multiple stages of development in a more natural 3D environment compared with traditional 2D cell cultures.
The researchers, which included first author Ryan Walsh, PhD, grew the PVALB+ cortical interneurons in the lab by first creating two types of forebrain-like structures called forebrain assembloids: dorsal forebrain (dFB) and ventral forebrain (vFB) organoids. These organoids are created from human pluripotent stem cells. When fused, the forebrain assembloids supported the development of the fast-spiking human PVALB+ cortical interneurons. Identifying some defects associated with schizophrenia could provide new insights into the early stages of the disease and help in developing better treatments. Read more in Neuron.
This stem cell-related advance is the latest of many produced by Dr. Studer, Director of MSK’s Center for Stem Cell Biology, to study and potentially treat brain diseases. In April 2025, he was part of a collaboration reporting promising early results from a clinical trial testing stem cell–based therapy to treat Parkinson’s disease.
Transcription factor 19 is critical for the responses of NK cells to viral infection
Natural killer (NK) cells are considered to be part of the innate immune system and play a critical role in defending a host against viruses. Over the past decade, NK cells have also been discovered to behave like adaptive immune cells, responding to specific antigens and remembering past infections — but the transcriptional programs and regulators governing these responses are largely unknown.
Now researchers at MSK’s Sloan Kettering Institute have identified transcription factor 19 (TCF19) as one key player in driving a transcriptional program that coordinates the innate and adaptive NK cell responses against viral infection.
The study — led by first author Celeste Dang, a graduate student in the lab of senior author Joseph Sun, PhD — examined the process in mice infected with cytomegalovirus. The research team found that when TCF19 was removed in novel transgenic mice, NK cells weren’t able to properly mobilize to defend against the virus and that the calcium signaling crucial to the NK cells’ response was short-circuited.
The findings advance the understanding of immune responses in health and disease, and could inform the development of immunotherapies. Read more in Nature Immunology.