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 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.

The NFXF offered 10 Junior Investigator Awards for 2022, sponsored in part by the NFXF Heartland Chapter, and are listed below. If you have any questions about the awards, please contact us.

Each of our Junior Investigators will:

  • Meet with other Junior Investigators and NFXF team members prior to the conference taking place July 14-17, 2022, in San Diego, during a one-hour Zoom session.
  • Receive a complimentary professional registration to attend the International Fragile X Conference ($500 value), taking place July 14-17, 2022, in San Diego.
  • Present a poster presentation during the conference.
  • Attend the conference and write a summary of one research presentation as assigned by the NFXF. The family-friendly summary will be published by the NFXF post-event.

2022 Junior Investigators

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 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 (FXTAS) is caused by the expansion of a CGG trinucleotide repeat to a pre-mutation range of between 55-200 repeats in the 5’UTR of the FMR1 gene. Multiple lines of evidence suggest that 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 which accurately inhibit 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 (FXS), 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 (FXS), 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 questions 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 disease and essential tremor

Affiliation: Rush University

Project Summary: Fragile X-associated tremor/ataxia syndrome (FXTAS) may be misdiagnosed as Parkinson disease (PD) or essential tremor (ET) due to overlapping motor symptoms. Therefore, we sought to compare FXTAS, PD, ET and controls using quantitative measures of gait under fast speed and dual-task conditions to reveal subtle gait impairments. Distinct gait profiles in FXTAS, PD, and ET 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 (FXS). 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 FXS. 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. 

LEARN MORE

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.

Hilary Rosselot headshot

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

Last Updated: 5/13/2022

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