Summary Reports from 2015 Summer Student Fellowship Research Fund Studies

This summer, the NFXF funded four summer student research fellowships at $2500 each through the  Summer Student Fellowship Research Fund.

Since its inception in 2000, the fund has awarded $225,000 to 90 students focused on advancing the knowledge and understanding of Fragile X.

Today, we’re proud to present the four summaries of this year’s award recipients.

Cellular and Biomolecular Characterization of Fragile X Patient Induced Pluripotent Stem Cell Derived Neurons

Kanisha Desai

Emory University
Mentor: Dr. Gary Bassell

The loss of the Fragile X mental retardation protein (FMRP) in Fragile X syndrome has been linked to an increase in protein synthesis and increased activity of the phosphoinositide-3 kinase (PI3K) signaling pathway. Previous work in the Bassell lab has shown that FMRP directly regulates the catalytic subunit of PI3K and that reduction of overactive PI3K signaling corrects specific deficits associated with FXS. During my summer project, I used control and FXS patient-derived induced pluripotent stem cells (iPSCs) to generate neurons. Work in progress has been to characterize cellular and morphological deficits in FXS iPSC-derived neurons and assess the potential therapeutic value of PI3K inhibition.

The Effect of Genetic Background on Kv4.2 Expression in FXS Mouse Models

Nada El-Sayed

Cincinnati Children’s Medical Hospital Center
Mentor: Christina Gross, PhD

Fragile X syndrome (FXS) is often characterized by hyperactivity and is associated with epilepsy, especially in children. The underlying molecular causes of this hyperactivity remain unknown. Kv4.2, a protein that helps transmit signals between nerve cells, is a key regulator of nerve cell activity in the brain. My lab has previously shown that in a mouse model of FXS, levels of Kv4.2 are decreased. In pilot studies, which were part of my summer research, we showed similarly decreased Kv4.2 levels in another mouse model of FXS suggesting that reduced Kv4.2 function could contribute to neuronal hyperactivity and epilepsy in FXS.

My research this summer focused on regulation of Kv4.2 production, as identifying ways to increase Kv4.2 levels could potentially lead to the development of novel treatment strategies for FXS. I worked with microRNAs, which are natural and selective inhibitors of protein production that lead to reduced protein levels of their targets. I was able to confirm regulation of Kv4.2 by a specific microRNA. By inhibiting this microRNA in the future, we could potentially increase Kv4.2 expression in patients with FXS, which may help to reduce neuronal hyperactivity.

Effects of Cognitive Function and Dual-Task Interference on Balance and Gait in Premutation Carriers of the Fragile X Mental Retardation 1 Gene

Erin Robertson-Dick

Rush University Medical Center
Mentors: Joan A. O’Keefe, PT, PhD and Deborah A. Hall, MD, PhD

My summer project was to determine the impact of cognitive interference on balance and gait function in carriers of a premutation on the Fragile X mental retardation 1 (FMR1) gene compared to age matched healthy controls. I did this using dual-task gait and balance paradigms involving i-SWAY and i-WALK inertial sensor testing in conjunction with neuropsychological assessments of executive function. My results showed no significant differences in dual-task interference between the two groups, likely due to low sample size. However, I am continuing to collect data in order to increase my sample size.

Institute A Controlled Trial of Sertraline in Young Children with Fragile X Syndrome

Sarah Fitzpatrick

UC Davis MIND
Randi Hagerman, MD

My project involved managing the extensive process of completing a trial of sertraline in young children with FXS by bringing in the final subjects and preparing the data for analysis. The analysis is complete and we are currently writing the paper for publication. In addition, I collaborated with many brilliant people, shadowed Dr. Hagerman in patient visits, learned about the Fragile X field, and developed important research, clinical, and management skills. Ultimately, I discovered my passion for working with families affected by Fragile X and greatly look forward to specializing in FXS as a physician and researcher in the future.