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An Upstate first: PhD candidate studying brain dysfunction wins prestigious NIH transition award

After building a research project studying empathy loss related to dementia, Aya Kobeissi has been awarded a Predoctoral to Postdoctoral Fellow Transition Award (F99/K00) from the National Institute of Health (NIH). The NIH awards seeks to “encourage and retain outstanding graduate students who have demonstrated potential and interest in pursuing careers as independent researchers.”

A first for an Upstate graduate student, this award provides up to six years of funding for the completion of dissertation research and during the postdoctoral phase, helping students transition into successful, independent research scientists.

Kobeissi has been honored for her research previously; she is also the  recipient  of the prestigious Diana Jacobs Kalman Scholarship from the American Federation for Aging Research.

Life-Changing and Incurable

Kobeissi is currently studying dysfunction in the prefrontal cortex; specifically, what causes behavioral variant frontotemporal dementia (bvFTD)-associated symptoms. FTD is a type of dementia that affects the frontal and/or temporal lobes of the brain, leading to the deterioration of these areas over time. It is the most common cause of dementia for people under 60 and the second most common after Alzheimer's disease. The most common type is the behavioral variant, which makes up about 50% of FTD cases. bvFTD leads to significant changes in personality, poor judgment, inappropriate social behavior, and a lack of emotional responses, including a loss of empathy, which is one of the most distressing symptoms.

Restoring Empathy

Her work focuses on mutations of the C9orf72 gene; discovered to be one of the most frequent genetic causes of FTD in humans. Mutations in C9orf72 lead to several pathologies, including the formation of dipeptide repeat (DPR) proteins. She’s been working with a mouse model that mimics one of the DPRs.  

“Of those DPRs, polyGR is one of the most toxic and that's the focus of my research,” explains Kobeissi. “We found that these mutant mice exhibit hallmark behavioral symptoms of bvFTD, including a loss of empathy-driven consolation towards distressed partners.  Further, excitatory neurons in the dorsomedial prefrontal cortex (dmPFC) are hypoexcitable and display abnormal ion channel properties. 

"A single dose of the social hormone oxytocin can restore consolation and neuronal excitability in our bvFTD mouse model," she continues. "These exciting results suggest that oxytocin has promise as a novel non-invasive therapeutic strategy to treat loss of empathy in bvFTD.  For the remaining year of my dissertation, we are investigating the detailed neurophysiological mechanisms that underly lost consolation and how oxytocin can restore these behavioral and neurophysiological deficits.”

Motivation from Curiosity

Her advisor, Wei-Dong Yao, Distinguished Professor of Psychiatry and Behavioral Sciences, highlights how impressive Kobeissi’s success in winning this NIH award is.

“They not only look at what you have accomplished, but also your potential,” he says. “They’re supporting bright, young scientists."

Kobeissi credits Yao’s commitment to letting students explore research that interested them as a factor in her success.

“Along the way, there's a lot of positive learning experiences that happen,” she explains. “You learn about the science, you explore your interests, and you build your skillsets. You learn how to become an independent thinker and think critically.”

“That's essentially the nature of research,” says Yao. “The motivation comes from curiosity.”

Yao continues; “I usually do not like the model in which the students come in, you give them a project, and they work on for five, six years. That’s less exciting, right? You start with several projects, you compare, you explore, and you focus on something that you are really interested in.”

Kobeissi plans to continue to look deeper into the mechanisms of bvFTD.

“The symptoms of bvFTD typically start in middle age, so there seems to be an age dependent component," she said. "The next questions I want to explore are what is it about aging that's causing these deficits and why don't younger people exhibit these behavioral symptoms even though they harbor FTD-associated genetic mutations?” She plans on exploring these questions during her post-doctoral studies, characterizing changes in the neurophysiology and associated molecular signatures underlying bvFTD to elucidate age-dependent processes that contribute to bvFTD. 

You can read more about the Yao lab here.

Caption: Aya Kobeissi is the first Upstate graduate student to receive the NIH Predoctoral to Postdoctoral Fellow Transition Award.

 

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