Congratulations to our 2026 Junior Investigators! These rising stars in the Fragile X field will join us at the NFXF 20th International Fragile X Conference, where they’ll have the opportunity to present their research and connect with the broader community.
If you see them at the conference, be sure to say hello!
The Jr. Investigator Awards exist to invest in the future of Fragile X research and treatment — providing emerging professionals with the experience of attending, networking, and presenting at the NFXF International Fragile X Conference.
The NFXF is proud to support them as they grow into the next generation of Fragile X experts.
Join Us in Celebrating Our 6 Jr. Investigator Awardees!
Project Title: Insights into Disease Pathogenesis from FXTAS Patient iPSC Derived Neurons
Affiliation: University of Michigan
Project Summary: FXTAS results from a transcribed CGG repeat expansion in FMR1. The mechanisms of pathogenesis in human remain enigmatic. Here we generated human FXTAS iPSC-derived Neurons and corresponding isogenic control lines where the repeat has been removed. Using these gene-specific controls, we observe differences in neuronal activity and physiology, with survival studies still ongoing. We propose that this platform provides a valuable tool for assessing the mechanisms underlying FXTAS pathogenesis and a useful tool for secondary screening of potential FXTAS therapeutic strategies.
Project Title: Mental Health Symptoms, Medication, and Service Use Among Young Women with Fragile X Syndrome
Affiliation: University of Texas at Austin
Project Summary: This study explored mental health symptoms, medication, and service use among 13 young adult women with Fragile X syndrome (FXS), aged 17-25 years. Caregivers reported a high frequency of depression symptoms, while only 38% of females were on a medication to target depression or anxiety, 25% of females were receiving psychological services for their mental health challenges, and 54% received neither. This work is essential for addressing an overlooked need in young women with FXS and has implications for establishing evidence-based interventions for this population as well as promoting policy that allows these services to be easily accessible.
Project Title: Unraveling the Root Cause of Fragile X Syndrome by R-loop Mediated Epigenetic Mechanisms on Repeats
Affiliation: Johns Hopkins School of Medicine
Project Summary: Fragile X syndrome arises from epigenetic silencing of FMR1 caused by CGG repeat expansion. We identified approaches to shorten the repeats and reactivate FMR1 in human ES and iPS cells carrying the full mutation. Treatment with defined small molecules restored FMR1 mRNA and FMRP protein while inducing contraction of the expanded repeats. R loop formation by catalytically dead Cas9 was necessary and sufficient for contraction, promoting DNA demethylation and transcriptional reactivation, which further increased R loops in a self-reinforcing feedback loop. Repeat contraction was dependent on the DNA mismatch repair pathway. RNA seq confirmed specificity, highlighting a therapeutic path without nuclease-mediated genome editing.
Project Title: Effects of Kv3 Positive Modulators on EEG Biomarkers in FMR1 Knockout Mice
Affiliation: Cincinnati Children’s Hospital Medical Center
Project Summary: We investigated the effects of Kv3 potassium channel positive modulators (AUT00206 and AUT00201) on EEG biomarkers in FMR1 knockout mice. Preliminary analyses indicate both compounds reduced resting gamma power, steepened aperiodic slope, and enhanced auditory steady-state phase-locking relative to Vehicle, consistent with improved fast-spiking interneuron function and restored excitatory-inhibitory balance. These translatable EEG biomarkers support Kv3 modulation as a therapeutic mechanism for sensory processing deficits in Fragile X Syndrome. Compounds provided by Autifony Therapeutics Ltd.
Project Title: Diagnosis of the FMR1 Premutation in a Cohort of Children with Neurodevelopmental Disorders: Definition of a Pediatric Clinical Phenotype
Affiliation: Parc Tauli Hospital, Barcelona
Project Summary: The clinical and neuropsychiatric features of the FMR1 gene premutation (55–200 CGG repeats) remain poorly defined in children, despite its relatively high prevalence in the general population. This study aimed to investigate the prevalence of the FMR1 premutation in a cohort of children with neurodevelopmental disorders and to describe the associated clinical phenotype, contributing to a better understanding of its role and impact in pediatric neurodevelopmental conditions and potential implications for diagnosis and clinical management.
Project Title: Reduced Steady State Responses in Fragile X Syndrome Highlight Difficulties with Stimulus Representation Maintenance That are Linked to GABAergic Mechanisms
Affiliation: Rush University Medical Center
Project Summary: Fragile X syndrome (FXS) is characterized by sensory hypersensitivities and atypical auditory processing, particularly in the gamma frequency range. We examined the 40-Hz auditory steady-state response (ASSR) measured with EEG in adolescents and adults with FXS compared to matched typically developing controls. Results indicate reduced neural entrainment and impaired stimulus representation maintenance in FXS, with uniformly diminished responses across stimulus duration relative to the robust transient-to-sustained response observed in controls. Findings highlight altered temporal precision of auditory synchronization in FXS and suggest underlying disruptions in excitatory–inhibitory neural balance related to altered GABAergic modulation.
