NFXF Summer Scholar Research Awards

The National Fragile X Foundation (NFXF) funds one or more summer student research at $2,500 each. The work can be in the area of Fragile X syndrome (FXS), Fragile X-associated tremor/ataxia syndrome (FXTAS), or Fragile X-associated primary ovarian syndrome (FXPOI).

These awards are meant to introduce undergraduate students or students in professional training programs to research in the Fragile X field by providing funding for a summer project that adds to the body of knowledge around Fragile X in a meaningful way while providing a distinct training experience.  Projects can be new or existing. Once completed,  each awardee will summarize their summer project in a 15-minute video presentation.

2021 Summer Scholars

Congratulations to our four NFXF Summer Scholars!

Watch each of the 15-minute presentations here.

Collis Brown

Potential Drug Therapy for Fragile X Tremor/Ataxia Syndrome

Affiliation: Howard University, Department of Pharmacology
Supervisor: Dr. Tamaro Hudson

John Burwinkle

MicroRNA-Mediated Correction of Dendritic Spine Abnormalities in a Mouse Model for FXS via Modulation of Cytoskeletal Proteins

Affiliation: Cincinnati Children’s Hospital Medical Center
Supervisor: Dr. Christina Gross

Bonnie McKinnon

The Diagnostic Experience of Women with Fragile X-Associated Primary Ovarian Insufficiency (FXPOI)

Affiliation: Emory University, Department of Human Genetics
Supervisor: Dr. Emily Allen

Elizabeth Saoud

A Study of Visual Evoked Potentials in Children with Fragile X Syndrome

Affiliation: Boston Children’s Hospital, Harvard Medical School
Supervisor: Dr. Carol Wilkinson

2018 Scholars

Andrew Snider

Investigation of the Potential of AZD7325 Treatment on EEG Oscillations, Gamma Waveforms, and Dendritic Spine Morphology in the Mouse Model of FXS

Supervisor: Christina Gross, PhD

Hypothesis: We hypothesize that treatment with the GABAAα2/3 agonist AZD7325 will rescue increased gamma oscillations and abnormal dendritic spine morphology in FMR1 KO mice.

Aim 1 will analyze the effect of AZD7325 treatment on basal gamma EEG power in FMR1 KO mice and their WT littermates.

Approach: We will test the potential of the GABAAα2/3 agonist, AZD7325 (AstraZeneca), on normalizing basal EEG levels and, in particular, the increased gamma EEG power observed in FMR1 KO mice. 6-8-week-old FMR1 KO mice and their WT littermates will be implanted with cortical electrodes for continuous video/EEG recording using a wireless system from Data Sciences International. Three days after surgery, baseline EEGs will be recorded for a period of 7 days to confirm basal EEG waveforms in the mice. Then, the mice will be administered with daily injections 1mg/kg of AZD7325 or the vehicle control (0.05% SBECD (Sulfobutyletherbetacyclodextrin)) in Milli-Q water for 10 consecutive days (dose established by previous studies in mice). The recorded EEG data will be analyzed for individual waveforms, total power, and relative and absolute gamma oscillations using NeuroScore software. Feasibility of these experiments is confirmed by our previous publications using mouse EEG analyses (Gross et al., 2016), and preliminary data that recapitulate published data.

Aim 2 will examine the effect of treatment of AZD7325 on dendritic spine density and morphology.

Approach: Post completion of ten days of drug treatment and recording, the mice brains will be collected and preserved for analysis of dendritic morphology. The brains will be first treated through the Golgi staining process using the FD Rapid Golgi Staining Kit as we have done previously Gross et al., 2015b. Briefly brains will be sectioned using a vibratome (160 μm slices), stained according to the manufacturer’s protocol and dendritic spines of CA1 pyramidal neurons will be imaged using a widefield microscope using a 60X objective, and quantified using Image J (NIH). The dendritic spine counting techniques are routinely performed in the laboratory (Gross et al., 2015b). Most recently, we have used a similar treatment paradigm (10 days of daily dosing) with a different drug to show that dendritic spine density was reduced after treatment. [Figures not included.]

Kara Brown

Brain Microstates as a Window into Sensory Sensitivity in Fragile X Syndrome

Supervisor: Dr. Lauren Ethridge

This study will be the first to observe the microstates in FXS in both the resting and prestimulus states. We aim to 1) assess whether FXS, similar to ASD, maintain more stable microstates during resting EEG, and whether this is correlated with behavioral or sensory rigidity; and 2) assess whether pre-stimulus microstates affect sensory processing in FXS specifically associated with sensory hypersensitivity. We hypothesize that people with FXS will have more stable resting microstates and also will spend more time in an abnormal pre-stimulus microstate, potentially associated with increased activity in primary sensory cortices, leading to hyperexcitability and hypersensitivity to auditory stimuli.

Ryan Risgaard

Development and Screening of Novel Compounds for FMR1 Gene Reactivation

Affiliation: University of Wisconsin-Madison
Supervisor: Dr. Xinyu Zhao, Professor of Neuroscience

Developments in stem cell research and sequence-specific synthetic molecules have presented promising opportunities for potential drug therapies of Fragile X Syndrome (FXS). FXS is an X-linked genetic disease and the largest known cause of inherited intellectual disability. Caused by a CGG repeat expansion in the FMR1 gene, FXS results in hypermethylation and subsequent shutdown of gene activity and protein expression. Past therapeutic strategies have attempted to restore FMR1 activity through drug compound screens, but to date, no compounds have successfully, fully reactivated the FMR1 gene. To address this challenge, my mentor Dr. Zhao’s lab has created a luciferase-based reporter cell line that has allowed for the large-scale screening of compounds for FMR1 gene reactivation. Additionally, my co-mentor Dr. Ansari’s lab has successfully developed sequence-specific polyamides that have been shown to bind methylated DNA and reduce methylation of targeted sites. Design of a novel polyamide compound that binds and reactivates the FMR1 gene would represent a significant step towards therapeutic strategies of FXS. Therefore, this project will focus on (1) conducting a secondary screening of potential small molecule gene reactivators and (2) aiding in the development of novel polyamide compounds that bind CGG repeats and reduce methylation of the FMR1 gene.

Scholar Archives

Ellie Eckert

Social Gaze Differences in Fragile X Syndrome and Idiopathic Autism Spectrum Disorder

Supervisor: Craig Erickson, MD

There are a number of noted similar behaviors and social impairments between individuals with Fragile X syndrome and Autism spectrum disorder, so much so that roughly 30% of children with FXS also receive a diagnosis of autism. This study will investigate the fundamental differences in mechanisms that drive these behavioral features seen in both FXS and ASD, and may provide the basis to develop tools that will accurately measure social deficits specific to FXS. These findings will allow for future investigation into distinguishing features between FXS and ASD that may aid in accurate diagnosis and tailored treatment.

Ndeye Marieme Ndiaye

Social Reward Learning in Human Patients with Autism

Supervisor: Gül Dölen, MD, PhD

The recent development of a human version of the conditioned place preference (CPP) assay we use to measure the rewarding properties of social interactions in mice, dramatically improves the translational validity of neural mechanisms and therapeutic targets uncovered using this assay. Preliminary data collected in the Dölen lab indicates that FMR1 knockout autism and Fragile X model mice have impaired social reward learning. In collaboration with the Thompson lab, I will conduct experiments to test the hypothesis that patients with Fragile X and autism have a similar impairment in social reward learning, using the human version of the social CPP assay.

Marwa Zafarullah

Genomic Editing of FMR1 Premutation in Human Fibroblast Cell Lines via Delivery of Purified Cas9 Ribonucleoproteins

Supervisor: Flora Tassone, PhD

This study will help us to better understand the impact of the CGG repeats on the different clinical premutation phenotypes and the molecular mechanisms behind the development of Fragile X-associated disorders. The CRISPR Cas9 technology has a profound impact on research efforts including identification of genes as well as the development of new disease models. The genome editing by transient expression of Cas9 (as RNP) will permit the consideration of a range of delivery options for therapeutic applications. In the future, with the optimization of suitable delivery system and proper assessment of specificity, we can clinically translate this study for the therapeutic editing in the Fragile X-associated disorders. (Also see: CRISPR, a New Genome Editing Tool: Could it Work for Fragile X-Associated Syndromes?)

Joseph Krzeski

Testing MicroRNA-Mediated Silencing of Kv4.2 as Therapeutic Target in an FXS Mouse Model

Supervisor: Dr. Christina Gross

Mika Nagamoto and Jenna Nagamoto

Evaluation of a Direct Outcome Measure of Social Interaction in Children and Adults with Fragile X Syndrome

Supervisor: Nicole Tartaglia, MD

Chandler Robinson

Activity-Dependent Dysfunction of Microglia in Fragile X Syndrome

Supervisor: Craig A. Erickson, MD

Seokyu (Philip) Shin

Understanding the Role of Agranular Insular Cortex Projections to the Nucleus Accumbens in the Pathogenesis of Blunted Social Affect in Fragile X

Supervisor: Dr. Gül Dölen

Kanisha Desai

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

Affiliation: Emory University
Supervisor: 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.

Nada El-Sayed

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

Affiliation: Cincinnati Children’s Medical Hospital Center
Supervisor: 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.

Sarah Fitzpatrick

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

Affiliation: UC Davis MIND Institute
Supervisor: 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.

Erin Robertson-Dick

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

Affiliation:Rush University Medical Center
Supervisors: 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.

Salpi Siyahian

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

Affiliation: University of California, Davis
Mentor: Dr. Randy Hagerman

Salpi SiyahianI had the honor of working at the UC Davis MIND Institute as a research study coordinator under the mentorship of Dr. Randi Hagerman. The study I helped coordinate looked at the benefits of a low dose of sertraline, an SSRI that increases the level of serotonin, on language, anxiety, and social deficits in young children with Fragile X syndrome (FXS).

A preliminary analysis of the first 30 subjects showed improvements in cognition, language, and social behavior through significant improvements in the CGI-I, VAS, and Mullen assessments. Working on this project has reinforced my interest in targeted treatments in FXS and I am excited to see the positive impact of this study on the younger FXS population.

This study will continue to enroll children with FXS between the ages of 24-68 months until mid-January 2015.

Matthew Davenport

Excitatory/Inhibitory Modulation and the Fragile X Synapses

Affiliation: Cincinnati Children’s Hospital Medical Center
Mentor: Dr. Craig A. Erickson

Matthew DavenportI worked with Drs. Craig Erickson and Tori Schaefer to assess the efficacy of two GABA(A) modulators, which boost inhibitory signaling in the FMR1 knock-out mouse model of FXS. Deficiencies in inhibitory signaling, dendritic spine number and spine morphology are suspected to contribute to the pathophysiology of FXS in both patients with FXS and in mouse models.

My work included the chronic treatment of FNR1 knock-out mice, collection and processing of brain tissue, microscopy and quantification of dendritic spine density and characterization of spine morphology.

Preliminary data indicate a differential effect of the therapeutics on the FXS dendritic spine phenotype, likely related to the different specificity of the drugs to regulate inhibitory signaling. Further studies evaluating the effects of these drugs on neural physiology and behavior are currently ongoing.

Whitney Espinel

Improving Health Education for Women Who Carry an FMR1 Premutation

Affiliation: Emory University School of Medicine
Mentor: Dr. Stephanie Sherman

Whitney EspinelMuch of the current research on the FX premutation is focused on defining health risks (e.g. FXPOI/FXTAS) and less is dedicated to understanding the personal experiences of women seeking to understand and navigate their own health journey.

My project used focus group discussions to uncover both barriers and facilitators faced by women who carry the premutation when seeking medical care. We uncovered many barriers to personal healthcare including the lack of knowledge among medical providers, inability to keep pace with findings from research in the field, and the shortage of premutation-specific educational materials and support.

The second half of this project aims to create and distribute premutation-specific educational materials for women. Many premutation carriers face the task of educating not only themselves but also healthcare providers and family members. Having access to up-to-date materials can help diminish misperceptions regarding health risks and aid in information sharing and awareness.

Stefan Sweha

Genetic Markers Predictive of Sertraline Treatment Response in Young Children with Fragile X Syndrome

Affiliation: Department of Biochemistry and Molecular Medicine, University of California, Davis
Mentor: Dr. Flora Tassone

Young children with FXS can present with anxiety, irritability, and hyperactivity related to sensory hyperarousal and language delay. Recently, Winarni et al. (2012) reported that treatment with Sertraline led to improvement in expressive language capability in boys with FXS. A positive response to sertraline was recently observed (Winarni et al., 2010) in young children with FXS and autism spectrum disorders. In addition, a preliminary analysis of children in a double-blind, placebo-controlled trial of sertraline in young children with FXS showed a marked improvement in anxiety.

In this study we determined if the genetic allelic variants of several genes related to the serotonergic pathway correlate with the observed clinical response. Data analysis is currently in progress.

Winarni TI, Chonchaiya W, Adams E, Au J, Mu Y, Rivera SM, Nguyen DV, Hagerman RJ. (2012) Sertraline may improve language developmental trajectory in young children with Fragile X syndrome: a retrospective chart review. Autism ResTreat. 104317. doi: 10.1155/2012/104317.

Ben King

Affiliation: Stanford University
Mentor: Dr. Allan Reiss

Ben KingThis summer, I worked with CIBSR at Stanford University under director Dr. Allan Reiss and project manager Mai Manchanda on a double-blind, placebo-controlled trial of donepezil in Fragile X syndrome (FXS). My work included administering and scoring behavioral and cognitive outcome measures to study participants with a focus on the CNT as well as aiding with the collection of neuroimaging data, including structural and functional MRI and near infrared spectroscopy (NIRS). Furthermore, I carried out structural MRI data editing and quality checking using the brain imaging software FreeSurfer 5.3, a semi-automated anatomical parcellation and segmentation tool.

Based on preliminary analyses of CNT data, donepezil had no effect on cognition in FraX. However, our study utilized many other behavioral/cognitive outcome measures beyond the CNT that must be analyzed to further determine whether donepezil enhances cognition or behavior in FraX.

Liqi Shu

Affiliation: Emory University School of Medicine
Mentor: Peng Jin

Liqi ShuGiven the high prevalence of Fragile X premutation carriers among the general population and the high risk of developing FXTAS among the male carriers, it is important to develop therapeutic intervention for FXTAS. Using our established assay, we screened multiple libraries, and identified and validated 34 small molecules. Some of them have the unknown biological activities while others have been implicated in different biological pathways, which will be further tested in the mammalian system in the near future. Our studies should provide new insight on the therapeutic development for FXTAS.

Hayley McCausland

Hayley McCauslandFragile X syndrome is characterized by hyperactivity, and about 25% of patients have epilepsy. FMRP, the protein lost in Fragile X, regulates many different functions in nerve cells. One of its targets is Kv4.2, a protein that is critical for the activity of brain cells. Abnormal levels of Kv4.2 in FXS patients may contribute to the cause of epilepsy. My project was to determine how Kv4.2 is regulated by FMRP. The results suggest a new model for the regulation of Kv4.2 by FMRP.

Zaynah Sadiq

Quality of Life as an Outcome of Developmental Trajectories in Fragile X During the Transition from Adolescence to Adulthood

Affiliation: Stanford University School of Medicine

Michelle Frazer

Correction of Behavioral Phenotypes in FXTAS Model Mice

Affiliation: University of Michigan

Cynthia Chen

Structural Basis for the Recognition of RNA by the Fragile X Mental Retardation Protein, FMRP

Affiliation: Massachusetts Institute of Technology

Scott Danielson

Targeting Excess PI3K Signaling to Rescue Dendritic Spine Morphology in a FXS Mouse Model

Affiliation: Emory University School of Medicine

Annie Pally

FMRP Regulation of the Central Mevalonate Pathway in a Fragile X Mouse Model

Affiliation: University of Houston

Emily Liang

Evaluating FreeSurfer as an Analysis Tool for Longitudinal Structural MRI in Young Adults with FXS

Affiliation: Stanford University

Questions?

If you have questions about anything research-related, we’d love to hear from you! You can reach out to Hilary Rosselot directly, or submit your question or comment through our contact form below.

Hilary Rosselot headshot

Hilary Rosselot,
Director of Research Facilitation
hilary@fragilex.org
(202) 747-6208

Last Updated: 8/31/2021