NFXF Junior Investigator Awards: Helping Secure the Future of Fragile X Scientific Research
The NFXF is committed to promoting scientific and treatment research advancements for Fragile X-associated conditions and disorders through our research facilitation programming, which includes our NFXF Junior Investigator awards. This program exists to promote and grow future research and treatment professionals in the Fragile X field by providing the invaluable experience of attending, networking, and presenting at the NFXF International Fragile X Conference.
If you have any questions about the awards, please contact us. We also have archives of past Jr. Investigator awardees.
Our 2024 Jr. Investigators are:
Lisa DeStefano, PhD
Affiliation: Cincinnati Children’s Hospital
Visual Discrimination in FXS: Insights From Behavior and EEG
Project Summary: Sensory abnormalities are common in Fragile X syndrome, including in the visual domain. To understand this better, participants completed a task in which they viewed a visual stimulus moving to the left or right and pressed a button corresponding to the direction of movement. In half of the trials, an auditory distractor was present. In FXS, we found that males performed worse with the distractor present, but females continued to improve. EEG analyses suggest that FXS males have an exaggerated brain response to the appearance of the visual stimulus, but less change in later brain activity associated with movement.
Brett Dufour, PhD
Affiliation: UC Davis
Evidence for Widespread Loss of Parvalbumin Expressing GABAergic Interneurons Throughout the Human Fragile X Brain
Project Summary: Parvalbumin-expressing (PV+) interneurons, critical inhibitory cells in the brain, are reduced in number in human autism and epilepsy. Here, in the largest postmortem neuroanatomical study of the human Fragile X syndrome brain to date (9 FXS and 9 control), we tested the hypothesis that PV+ INs are also reduced in the FXS brain. The number of PV+ neurons were significantly reduced in FXS subjects by 40-81% across all regions of the brain that were examined, including six cortical regions, amygdala, and hippocampus. These results implicate PV+ IN loss as a mechanism underlying E/I imbalance in FXS and can guide the development of targeted therapeutics.
Nell Maltman, PhD
Affiliation: University of Arizona
Language Features Among Individuals with Symptoms of Fragile X-Associated Tremor/Ataxia Syndrome
Project Summary: Individuals with FXTAS have known cognitive and motor difficulties, but how language may be impacted in this population is poorly understood. The primary aims of this study were to determine (a) the extent to which males and females with FXTAS symptoms differed in their language use and (b) associations between language production and FXTAS symptoms. Language did not differ between sexes, but aspects of language use predicted symptom expression. Thus, language production may be a promising candidate measure for future clinical trials.
Caroline Dias, MD, PhD
Affiliation: Children’s Colorado
Cell-Type-Specific Effects of the Fragile X Premutation in Human Brain
Project Summary: Although animal models have been critical in revealing molecular mechanisms of cellular dysfunction in Fragile X-related disorders, understanding how the human brain is directly impacted remains unresolved. We conducted a cell type-specific transcriptomic analysis of postmortem human brains from individuals with Fragile X mutations and matched controls, sequencing over 120,000 nuclei from the frontal cortex and cerebellum (areas of the brain). We found evidence for cell type-specific, disease-specific, and regional-specific patterns of transcriptional and FMR1 protein (FMRP) network perturbations, including in oligodendrocytes, the key myelinating cells of the central nervous system.
Andrew Dakopolos, PhD
Affiliation: UC Davis
Developmental Links Between Cognition, Adaptive Behavior, and Intelligence in Individuals with Fragile X Syndrome
Project Summary: Individuals with Fragile X syndrome often experience challenges related to intellectual and adaptive functioning that may interfere with learning, independence, and living skills. While these areas of relative challenge are well-established, less is known about how they interact and relate to one another in development — particularly for people with FXS. The present study sought out to examine associations of developmental changes over two years in the domains of cognition, adaptive behavior (including socialization, communication, and daily living skills), and IQ.
Our previous work has established longitudinal associations of change between cognition, adaptive behavior, and IQ in a sample of 264 individuals with intellectual disability, and the purpose of the present study is to extend and examine these patterns of associations, specifically for individuals with FXS. This investigation represents a new and innovative approach to understanding specific developmental patterns in individuals with FXS.
Sarah Nelson Potter, PhD, CCC-SLP
Affiliation: RTI International
Correlates of Parenting Stress in Mothers and Fathers of Young Boys with Fragile X Syndrome
Project Summary: Many parents of children with FXS experience elevated levels of parenting stress due to the challenges associated with raising a child with significant delays. This study examined relationships among parenting stress and measures of individual and couple well-being, as well as child characteristics, for mothers compared to fathers of young boys with FXS. Overall, we found similar relationships between mothers’ and fathers’ parenting stress and the other measures. However, we found a significant relationship between parenting stress and child autism symptoms for fathers but not mothers, suggesting that the causes of parenting stress may not be the same for mothers and fathers.
Walker McKinney, PhD
Affiliation: Cincinnati Children’s Hospital
Results from a Double-Blind, Randomized, Placebo-Control Trial of lovastatin and Minocycline in Fragile X Syndrome
Project Summary: Single-dose drug trials in Fragile X syndrome can establish drug safety and identify small changes in behavior or brain function that help clinicians decide early on if a drug is working and for whom the drug may work best. We completed a placebo-controlled, double-blind, crossover, single-dose study of lovastatin and minocycline in 29 participants with FXS. Participants completed several measures of cognitive functioning and an EEG (a measure of brain function) before and after dosing. Both drugs were safe and well-tolerated. We discuss differences in behavior and brain function associated with the use of lovastatin or minocycline.
Kimaya Sarmukadam, PhD
Affiliation: University of South Carolina
Sensory Impairments Predict Anxiety Symptoms in Preschoolers with Fragile X Syndrome: A Cross-Sectional Study
Project Summary: Anxiety symptoms and sensory impairments are common features of Fragile X syndrome. However, the relationship between anxiety and sensory symptoms in FXS remains unknown. Therefore, the current study aimed to clarify the relationship between sensory symptoms and anxiety symptoms in 42 preschoolers with FXS and 35 typically developing preschoolers. Results suggest that children with FXS had significantly elevated sensory symptoms, and sensory symptoms predicted anxiety symptoms similarly in both groups. Further research is needed to determine how sensory symptoms impact the development of anxiety in children with FXS across childhood.
Scholar Archives
Kate Shelley, PhD
FXPOI Alters Omega-6 Fatty Acid Metabolism and Formation of Pro-inflammatory Metabolites Compared to FMR1 PM Carriers Without FXPOI
Affiliation: Emory University
Project Summary: Metabolomic analysis of blood plasma from female FMR1 premutation carriers revealed levels of omega-6 fatty acids and arachidonic acids are increased in women with FXPOI. The identified metabolites are linked to specific ovarian functions perturbed in the FMR1 premutation mouse ovary. We used both human and mouse data to investigate how CGG repeats lead to impaired function of the ovaries.
Maria Jimena Salcedo-Arellano, MD
Metabolic Profile in the Brain With Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)
Affiliation: University of California – Davis, MIND Institute
Project Summary: We analyzed changes in the concentration of primary metabolites, with emphasis in glucose and the gluconeogenesis pathway precursors, activators, and inhibitors, in the brain with FXTAS. We also investigated how these changes relate to the levels of Fragile X mental retardation protein, to the number of CGG repeats, and to the presence of the APOE ε4 allele.
Carolyn Yrigollen, PhD
Evaluation of a CRISPR Gene Editing Strategy in CGG Knock-In Mice
Affiliation: Children’s Hospital of Philadelphia
Project Summary: AAV delivery of FMR1 targeting CRISPR Cas9 and guideRNAs into the brains of CGG knock-in mice induced partial deletion of the trinucleotide repeats. These mice model FXTAS molecular and motor phenotypes. The CRISPR-treated mice showed rescued molecular and motor phenotypes compared to uninjected knock-in littermates. Next-generation Nanopore sequencing identified outcomes of in vivo editing including partial CGG repeat deletion and AAV integration events. These results inform the future development of CRISPR therapeutics for the treatment of FXTAS and other Fragile X-associated disorders.
Connor Maltby, PhD
Human Stem Cell Models for Investigating Disease Mechanisms of Fragile X-Associated Tremor/Ataxia Syndrome
Affiliation: University of Michigan
Project Summary: Fragile X-associated tremor/ataxia syndrome is caused by the expansion of a CGG trinucleotide repeat to a pre-mutation range of between 55 and 200 repeats in the 5’UTR of the FMR1 gene. Multiple lines of evidence suggest that the translation of a toxic repeat-associated polyglycine peptide, FMRPolyG, is a significant driver of toxicity in FXTAS. We have utilized genetic editing in patient-derived neurons to allow accurate detection of this product, which has allowed us to investigate how novel compounds that accurately inhibit the production of FMRPolyG lead to enhanced neuronal survival as well as restoring neuronal function.
Anubhuti Goel, PhD
Of Mice and Humans: Hypersensitivity to Distractors in Fragile X Syndrome
Affiliation: University of California – Riverside
Project Summary: Sensory hypersensitivity is one of the most prominent and disabling features of Fragile X syndrome, often limiting social interactions, delaying learning, and impeding daily functioning. Using a novel analogous task in humans with FXS and in FMR1-/- mice, we find that auditory distractors impair task performance to a greater extent in FXS than controls. Using two photon calcium imaging and EEG we also uncover the neural deficits that contribute to sensory hypersensitivity and distractibility, thus paving the way for targeted therapeutic strategies.
Sungeun Kang, PhD
Developing Improved Outcome Measures in FXS: Key Stakeholder Feedback
Affiliation: Cincinnati Children’s Hospital Medical Center
Project Summary: Since there are limited behavioral outcome measures of behavior inflexibility available for Fragile X syndrome, the Cincinnati Fragile X Treatment and Research Center (Dr. Schmitt) is in the process of developing a novel scale of inflexible behavior for FXS. For the instrument development, we invited individuals with FXS, families, and professionals to participate in focus groups to enhance validity by generating items significant and relevant to the population. In particular, we sought to incorporate caregivers’ experiences in reporting preexisting measures. Participants provided suggestions on question formats and contents, inclusion of certain items, and shared their challenges completing common measures.
Erin Robertson, PhD, AuD
Gait Impairments Distinguish Fragile X-Associated Tremor/Ataxia Syndrome From Parkinson’s Disease and Essential Tremor
Affiliation: Rush University
Project Summary: Fragile X-associated tremor/ataxia syndrome may be misdiagnosed as Parkinson’s disease or essential tremor due to overlapping motor symptoms. Therefore, we sought to compare FXTAS, Parkinson’s disease, essential tremor, and controls using quantitative measures of gait under fast speed and dual-task conditions to reveal subtle gait impairments. Distinct gait profiles in FXTAS, Parkinson’s disease, and essential tremor were found, which if confirmed may assist in more accurate and timely diagnosis and could be used to choose the most appropriate outcome measures for future clinical trials.
Tracy Jordan, PhD
Brain Anatomy in Child and Adolescent Girls With and Without Fragile X Syndrome
Affiliation: Stanford University
Project Summary: This study utilized MRI data to examine neuroanatomy in child and adolescent girls with and without Fragile X syndrome. Participants included 43 girls with FXS and 31 age- and verbal IQ-matched girls without FXS. Regional analyses revealed significantly different between-group volumes for bilateral caudate, pallidum, and accumbens such that the FXS group, on average, displayed increased brain area volumes. Exploratory analyses examining potential associations between brain region volume and key domains of social, affective, and cognitive development revealed differential patterns of associations between groups. Findings fill a critical gap in the literature by describing neuroanatomy among girls with FXS.
Michelle Tosin, PhD
Development of Fragile X-Associated Tremor Ataxia Syndrome Rating Scale (FXTAS-RS)
Affiliation: Rush University
Project Summary: We describe the stepwise methodology used for the development of a revised and improved version of the Fragile X-Associated Tremor/Ataxia Syndrome Rating Scale (FXTAS-RS) for motor signs assessment. We conduct a multimethod approach using Delphi panel and cognitive pretesting techniques to establish the five domains, 13 subdomains, and 18 items of the revised FXTAS-RS. We tested the revised version of the scale determining its readability, comprehensiveness, applicability, and relevance.
Talia Thompson, PhD
Using Qualitative Methods to Enhance our Understanding of Anxiety in Individuals with Fragile X Syndrome
Affiliation: University of Colorado
Project Summary: Qualitative research methods can generate hypotheses and highlight patient voices to convey a range of subjective life experiences. This electronic survey study aimed to describe the observable behaviors caregivers and self-advocates ascribe to anxiety in Fragile X syndrome. Qualitative findings from free-text responses elaborated and expanded upon quantitative results revealing new information on how individuals with FXS experience anxiety and how caregivers recognize symptoms. As regulatory agencies require proxy-reported measures to reflect the lived experiences of patients and their families, qualitative methods offer a promising approach to developing valid and patient-centered outcome measures without the overlay of researcher bias.
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.
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
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
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
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
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
Mentor: Dr. Randy Hagerman
I 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
Mentor: Dr. Craig A. Erickson
I 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
Mentor: Dr. Stephanie Sherman
Much 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
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
This 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
Given 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
Fragile 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
Michelle Frazer
Correction of Behavioral Phenotypes in FXTAS Model Mice
Cynthia Chen
Structural Basis for the Recognition of RNA by the Fragile X Mental Retardation Protein, FMRP
Scott Danielson
Targeting Excess PI3K Signaling to Rescue Dendritic Spine Morphology in a FXS Mouse Model
Annie Pally
FMRP Regulation of the Central Mevalonate Pathway in a Fragile X Mouse Model
Emily Liang
Evaluating FreeSurfer as an Analysis Tool for Longitudinal Structural MRI in Young Adults with FXS
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Randi J. Hagerman Summer Scholar Research Awards
The goal of the Summer Scholars program has always been to add to the body of knowledge around Fragile X in a meaningful way while providing a distinct training experience for future clinicians and scientists. Dr. Hagerman’s actions have contributed to the unmatched culture of collaboration in Fragile X today. Learn more about the Randi J. Hagerman Summer Scholar awards, and the person behind them.
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.
Anna De Sonia, Director of Research Facilitation
anna@fragilex.org