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Upstate neuroscientists awarded $3.6 million NIH grant to study role of new brain protein involved in social memory

Two Upstate Medical University neuroscientists have received a multi-million, multi-year grant from the National Institute of Mental Health to continue their work on the role of a new brain protein involved in social memory.

Julio Licinio, MD, PhD, MBA, and Ma-Li Wong, MD, PhD, both SUNY Distinguished Professors of Psychiatry and Behavioral Sciences and Neuroscience and Physiology, will continue researching how a plant gene functions in the mammalian brain with a $3.6 million five-year grant from NIH.

The pair had the paper “The epigenetic reader PHF21B modulates murine social memory and synaptic plasticity–related genes,” published in JCI Insight (https://insight.jci.org/articles/view/158081) last month.

In a previous paper published in Molecular Psychiatry, Licinio and Wong were the first to discover that a plant gene that guides plant root growth (PHF21B) is actually expressed in the mammalian brain and is regulated by stress.

This new paper, published July 22, shows that this gene and the protein it encodes regulates social behavior, synaptic proteins, and long-term potentiation (LTP).

Licinio said that LTP is a process involving persistent strengthening of synapses that leads to a long-lasting increase in signal transmission between neurons. It is an essential process in the context of synaptic plasticity. LTP recording is widely recognized as a cellular model for the study of memory.

Licinio said they were initially studying depression and had some initial clues from their studies that this plant gene could be involved in the risk to have depression.

“We then thought, what does a plant gene have to do with depression?” he said. “We decided to see if it was expressed in the brain, and to our surprise, it was. It’s part of a gene family that was initially found in plants, and its full name is plant homeodomain finger protein 21B. We showed that it was expressed in the mammalian brain and contributes to regulate the response to stress.”

This discovery came in 2016 and was the first paper to show this connection. After that, a team of German researchers took Licinio and Wong’s work a step further and showed that this same gene guides the development of neurons in the brain’s cortex. The researchers knocked down the gene and saw a disruption of that migration during development.

Licinio and Wong’s most recent paper builds on that first finding. They now discovered that knocking down the PHF21B gene impacts social memory. In their work, mammals deficient in the gene treated other animals like new each time they were introduced.

“We tried to show that this gene continues to be important throughout life,” Licinio said. “One of the potential implications is for disorders like autism or some psychiatric disorders where social memory is affected.”

The NIH grant will allow the pair and their team of researchers to continue this work.

“In the grant, we propose to understand the mechanism by which this gene disrupts social memory,” Wong said. “Some brain circuitries and specific brain areas are disrupted when this gene is deficient, so we are going to focus on those areas and try to understand the precise mechanisms by which social memory is impaired.”

“This gene has not been implicated in brain dysfunction before,” she adds.

The multi-year grant will give a significant boost to the research as well as put Upstate on the front lines of this cutting-edge research field.

“This grant is great for our work,” Wong said. “This funding will support the lab to take the next steps to understand the circuitries and novel regulatory mechanisms that modulate social recognition memory. This state of art research investigation joins other innovative studies at Upstate, strengthening Upstate’s standing at the forefront of neuroscience and psychiatry research.”

Adds Licinio: “People have been studying the same genes implicated in psychiatric disorders for 50, 60 years. They are implicated but don’t explain the whole thing, so we don’t have optimal treatments. Much research still needs to happen, and most researchers study the same old pathways. I think what’s really exciting about this is the innovation and that we are pursuing a new pathway that goes way beyond what people have been looking at.”

The team of researchers on the recently published paper includes the following participants from Upstate: Eunice W. M. Chin, PhD; Qi Ma, PhD; Hongyu Ruan, PhD; Camille Chin, PhD candidate-NEUP; Aditya Somasundaram (MS3); Chunling Zhang, MS; Chunyu Liu, PhD, and Wei-Dong Yao, PhD. In addition, national (Rutgers New Jersey Medical School and Medical College of Georgia) and international collaborators (Flinders University, South Australian Medical Research Institute, and the University of Adelaide) also contributed to the work.


Julio Licinio, MD, PhD, MBA, and Ma-Li Wong, MD, PhD, have been awarded a $3.6 million grant from the NIH to study the role of new brain protein involved in social memory.