Warren Winick-Ng named 2024 Donnelly Centre Home Fellow

Warren Winick-Ng, a research associate at the Donnelly Centre for Cellular and Biomolecular Research, is the 2024 recipient of the Donnelly Centre Home Fellowship.

Established from the estate of Robert Bertram Home, the fellowship invests in bold research ideas that are enabled by interdisciplinary collaboration across the Donnelly Centre. Winick-Ng is conducting research with Benjamin Blencowe, Canada Research Chair in RNA Biology and Genomics, Banbury Chair in Medical Research and professor of molecular genetics.

“On behalf of the Donnelly Centre Home Fellowship selection committee, I would like to congratulate Warren on receiving the prestigious Home Fellowship,” said Stéphane Angers, director of the Donnelly Centre and chair of the Donnelly Centre Home Fellowship selection committee. “Warren is a highly motivated and independent researcher who is making the most of collaboration opportunities at the Donnelly Centre and beyond. As the Home Fellow, his collaborative efforts in technological innovation will lead to tools of significant value to researchers interested in genomics.”

Winick-Ng spent much of his early academic career at the University of Guelph, from where he received an undergraduate degree in biomedical science and a master’s degree in neuroscience. He then pursued a PhD in physiology and pharmacology at the University of Western Ontario. His interests in psychology and neuroscience evolved during this time to focus more on genomics and nuclear structure.

With these new focus areas in mind, Winick-Ng started a postdoctoral position in 2017 under the supervision of Ana Pombo at the Max Delbrück Center for Molecular Medicine in Berlin. He spent five years at the Center studying cellular identity in the brain and the impact of addiction on brain cell specialization; his goal was to learn how DNA structure influences cellular function. To this end, one of his projects involved mapping DNA in the brain to detect differences in neural DNA structure in individuals with disease.

Winick-Ng decided to pursue a research associate position with Blencowe at the Donnelly Centre in 2023 after meeting and discussing their common interests in the link between genome structure and function and how it may come into play in autism spectrum disorder (ASD).

ASD is a highly heritable neurodevelopmental disorder caused, in part, by the dysregulation of processes required for the synthesis and maturation of messenger RNAs, which provide the instructions needed for a cell to produce proteins. Winick-Ng believes that the spatial organization of genes encoding messenger RNAs linked to ASD may play a role in this dysregulation.

Almost 10 years ago, the Blencowe lab found that the SRRM4 protein, which is responsible for activating the splicing of microexons that are critical for neuron development, is disrupted in individuals with ASD. Winick-Ng is investigating how the unique function of this protein might be connected to the dysregulation of spatial gene organization and microexon splicing in ASD patients.

“Ben allows me to be very independent and creative,” said Winick-Ng. “In fact, he encourages me to use my time as a research associate at the Donnelly Centre to pursue passion projects within our shared interests. He is particularly interested in cutting-edge approaches, which pushes me to develop and refine techniques needed to answer the difficult questions at the center of my research.”

Winick-Ng previously developed a technique that combined Genome Architecture Mapping with immunodetection, called Immuno-GAM, to study chromatin organization across the entire genome in the mouse brain. The new tool revealed a relationship between transcriptional activity levels and the 3D structure of very long genes that play critical roles in neural physiology, where higher activity levels result in greater loss of structure. The tool was also integral to the discovery that a single exposure to cocaine can result in changes to genome structure that persist for days, even after transcriptional processes recover.

In collaboration with Ahilya Sawh, assistant professor of biochemistry, Sabine Cordes and Jeffrey Wrana, professors of molecular genetics and Senior Investigators at the Lunenfeld-Tanenbaum Research Institute, and Ana Pombo, Winick-Ng is using a single-cell spatial transcriptomics technique, called MERFISH, as well as Immuno-GAM and RNA detection, to identify gene disruptions in both mouse models and human patients following the loss of the SRRM4 protein. Structural changes to DNA associated with these gene disruptions could then potentially be targeted for disease treatment.

“Current autism therapies focus on symptoms, with no treatments aiming to cure the condition,” said Winick-Ng. “These medical treatments are also not fully effective in alleviating issues experienced by autism patients, even when combined with behavioural therapies. We want to have a more long-lasting impact on patients by drilling down into the precise variants of neuronal activation genes that lead to increased risk for ASD.”

Winick-Ng is conducting the first large experiment of his research this Fall, which involves studying the spatial proximity of around 200 genes to each other and structures in the nucleus associated with transcriptional changes. He is working with the Simons Foundation to access post-mortem ASD patient samples that will help him determine if there is a direct link between structural differences in DNA and gene disruption.

“Warren has been a pleasure to work with over the last year-and-a-half, and I believe he has everything it takes to run a successful research group after he completes his projects at the Donnelly Centre,” said Blencowe. “Through Warren’s work, I believe we will gain a deeper understanding of how altered chromatin states and higher-order nuclear organization relate to RNA regulation in brain disorders like autism.”

The Donnelly Centre for Cellular and Biomolecular Research established the Robert Home Research Fellowship Fund to support current and future fellows. You can contribute to research conducted by early-career scientists who are making strides in biomedicine by donating to the fund.