By Hilary Rosselot

Congratulations to 2022’s five NFXF Summer Scholars — Andy King, Natalia Rivera Alfaro, Dominic DeBiasi, Jordan Norris, and Jessica Tang!

The Summer Scholars Research Awards are designed to introduce undergraduate and/or graduate students to the field of Fragile X research. We do this by funding summer projects that add to the body of knowledge around Fragile X in meaningful ways.

Our 2022 Awardees were asked to summarize their summer project in a 15-minute video presentation, and here they are.

Join us in celebrating the future of Fragile X research and thanking these students and their mentors for their dedication to Fragile X!

Andy King

Andy is a first-year student in the Emory University Genetic Counseling Training Program, supervised by Dr. Emily G. Allen, Emory University, Department of Human Genetics.

The Personal Healthcare Experiences of African American Women Who Carry a Fragile X Premutation


Our study explores the personal healthcare experiences of African American women who carry a Fragile X premutation. We conducted phone interviews with 20 African American women with a premutation. We asked about the barriers to accessing and receiving adequate healthcare that they have experienced, including treatment of any Fragile X-associated primary ovarian insufficiency (FXPOI) symptoms they may have.

Our study highlights particular healthcare disparities experienced by underrepresented women in Fragile X research and improves health outcomes for all women with a premutation.

In their own words:

“Our study investigates the personal healthcare experiences of African American women who carry the Fragile X premutation. Throughout the summer and continuing this fall, we are interviewing 8–10 women with a premutation to understand their experiences with healthcare, any barriers they have had in their care, their emotional health, and other factors impacting their experiences.

“Our preliminary results show that African American women experience a worry over their symptoms being taken seriously. This is a similar experience to other women studied previously. They have expressed the difficulties in sharing their diagnosis with family, which has led to lack of support and strained relationships. We have also found that most participants endorse experiencing anxiety and depression throughout their experiences, with various approaches to care that has helped address these symptoms.

“We hope our research deepens our knowledge of underrepresented women’s experiences in genetic research, particularly in the Fragile X community.”

—Andy King, Emory University

Natalia Rivera Alfaro

Natalia is junior at the Universidad Nacional Autónoma de México, majoring in Genomic Sciences, supervised by Dr. Peng Jin, Emory University School of Medicine, Department of Human Genetics.

Searching FXTAS Genetic Modifiers by Combining Whole Genome Sequencing and Drosophila Model


Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative genetic disorder. People with FXTAS suffer from cognitive decline, tremors and ataxias (difficulty with balance and coordination). It is caused by CGG trinucleotide repeats, which are associated with the Fragile X mental retardation gene (FMR1).

The number of CGG repeats can cause Fragile X syndrome (with over 200 repeats) or FXTAS (between 55 and 199 repeats). However, people with the same number of repeats can show differences in the degree of expression of certain traits, this means that one person can have complete FXTAS and another one only mild symptoms even though they have the same number of repeats (this is known as incomplete penetrance).

We hypothesize that there may be other genes involved in FXTAS that affect how much it is expressed. We use the genomic information of 100 patients with FXTAS and 100 controls with mild expression of FXTAS. We then compare patients and controls to find a list of candidate genes that may be modulating the incomplete penetrance. Finally, we use fly models to see what happens if each candidate gene is overexpressed or depleted in combination with FXTAS. This allows us to determine which of the candidate genes are involved in the modulation of FXTAS.

This study will help interpret the genetic architecture of neurodegeneration, both associated with FXTAS and ataxia in general, as well as provide the opportunity for early intervention that may delay or prevent the onset of FXTAS.

In their own words:

“This summer I had the amazing opportunity of working with fly models in order to investigate the mechanisms responsible for the incomplete penetrance seen in FXTAS patients. I worked with various fly lines that knock down genes that we know are different between patients with mild FXTAS symptoms and patients with more severe symptoms in order to test their interaction with the CGG repeats. This will hopefully give us some interesting genes to look at more in depth in order to understand the reasons behind the incomplete penetrance of FXTAS.

“As an international student I also learned a lot from the American culture and work style and I am overall very thankful for this opportunity.”

—Natalia Rivera Alfaro, Universidad Nacional Autónoma de México

Dominic DeBiasi

Dominic is a senior at the University of Michigan, double majoring in Biopsychology, Cognition, and Neuroscience and Molecular, Cellular, and Developmental Biology, supervised by Dr. Peter Todd, University of Michigan, Department of Neurology.

Unraveling the Role of Repetitive RNA and RANprotein in FXTAS


Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease that stems from multiple copies of a short sequence in the FMR1 gene. Within a mid-range of copies, there exists an unorthodox way to make protein that would not be expected to be produced otherwise. Whether this “new” protein plays a role in the disease pathology remains unknown; therefore, this project provides insight as to whether this protein is sufficient to drive neurodegenerative-like phenotypes.

In their own words:

“I am incredibly grateful to have been selected as a Randi J. Hagerman National Fragile X Foundation Summer Scholar. The award provided me with the opportunity to engage in exciting research and gain experience working in the lab, but more importantly, introduced me to the wonderful Fragile X community. Throughout the course of this project, I’ve learned that community outreach and communication is just as important as the scientific research itself, if not more so. Organizations like the NFXF help to bring issues of human disease and medicine to the forefront, creating a bridge between the scientific community and the public, which results in huge impacts for treating these diseases that afflict so many.”

—Dominic DeBiasi, University of Michigan

Jordan Norris

Jordan is a second-year doctoral student of Cellular and Behavioral Neurobiology at the University of Oklahoma, supervised by Dr. Lauren Ethridge, University of Oklahoma, Department of Psychology, University of Oklahoma Health Sciences Center, Department of Pediatrics.

ROC Analysis of Biomarker Combination in Fragile X Syndrome-Specific Clinical Trials: Evaluating Treatment Efficacy via Exploratory Biomarkers


Clinical trials, specifically phase 2 clinical trials, are important steps in the process of developing novel treatments that are specific to Fragile X syndrome (FXS) and treating underlying causes of FXS over treating symptoms, alone. The goal of treating the source of FXS is to create long-term shifts that improve the quality of life of patients with FXS and their loved ones. Phase 2 clinical trials aim to establish safety and tolerability, but also give an indication in a relatively small group of individuals of whether the treatment is working.

A recent phase 2 clinical trial of the drug BPN14770 showed cognitive improvements through treatment, but measures of drug effects on brain function were relatively small. The study aims to revisit these physiological measures and assess them using a classification method that combines multiple brain function measures. We propose that combinations of brain function measures may give us a better idea of the complex interplay between individual characteristics of those with FXS and their response to treatment.

In their own words:

“Being an NFXF Randi Hagerman Summer Scholar recipient is an amazing opportunity to work on a project that may have important implications for Fragile X Syndrome–specific clinical trial methods and for the specific outcomes of the recent, successful phase 2 clinical trial testing BPN14770 (now zatolmilast). Specifically, it gave me the time to take a data-driven approach to biomarker selection where multiple biomarkers can be assessed without additional statistical strain.

Clinical trials, specifically phase 2 clinical trials, are important steps in the process of developing novel treatments that are specific to FXS and treating underlying causes of FXS over treating symptoms, alone. Developing feasible methods for FXS-specific clinical trials is an important step in evaluating the gap between known pharmaceutical mechanisms and measurable behaviors/clinical outcomes, especially when methodological issues arise. The chance to serve as a summer scholar allowed me to take these important first steps with existing clinical trial data with the hope that these results make a lasting impact on the way that we approach the measurement of pharmaceutical effects in FXS clinical trials.”

—Jordan Norris, University of Oklahoma

Jessica Tang

Jessica is a first-year medical student, University of California Davis School of Medicine, supervised by Dr. Paul Hagerman, Distinguished Professor of the Department of Biochemistry and Molecular Medicine and MIND Institute UC Davis School of Medicine

Transcriptional Gene Silencing of FMR1 as a Treatment for Fragile X-Associated Tremor/Ataxia Syndrome


Fragile X-associated tremor/ataxia syndrome (FXTAS) is caused by an abnormal Fragile X (FMR1) gene that produces high levels of the Fragile X protein (FMRP) that leads to neurodegeneration. We propose a gene therapy to knock out the abnormal FMR1 gene and, in follow-on work, add a coding cassette comprising a mini-promoter and FMRP coding region.

The goal of my project is to identify the RNA sequence(s) that can successfully target and silence the abnormal FMR1 gene. To do this, I package multiple RNA candidates into small (nano)particles that are then delivered to fibroblast cells. After the fibroblasts have grown for 1 week, 4 weeks, and 8 weeks, I will quantify how much FMR1 RNA and protein are produced by the fibroblasts. This allows us to determine how effective a given candidate sequence is in silencing the FMR1 gene. From my results, we will select the candidate RNA to be used in subsequent studies to silence FMR1 in rat and rhesus models. Our long-term goal is to develop a genetic therapy that will prevent neurodegenerative difficulties in patients with FXTAS by targeting the expression of the abnormal FMR1 gene.

In their own words:

“During my first year of medical school, I worked with Dr. Randi Hagerman, helping out with clinical trials and shadowing her through patient visits. This summer through the RJH NFXF Summer Scholar Program, I had the amazing opportunity to work under Dr. Paul Hagerman and see the translational science side of research — something that is often difficult to do during the school year.

“This summer, I am proud to have created a pipeline for identifying and screening small transcriptional gene silencing-RNAs (sTGSs) for gene therapy in Fragile X and FXTAS. Furthermore, I was able to identify two potential sTGSs that could lead to long-term suppression of abnormal FMR1 gene.

“Thank you NFXF for providing a platform to share my work and for supporting my aspirations of becoming a physician in academic medicine. I am so excited to continue working in the field of Fragile X among amazing mentors and leaders of their field!”

—Jessica Tang, University of California Davis School of Medicine

Congratulations Andy, Natalia, Dominic, Jordan, and Jessica! We can’t wait to see what your futures hold.

Author Hilary Rosselot

Hilary Rosselot
Hilary joined the NFXF team in 2019. Prior to joining the NFXF team, she worked at the Cincinnati Fragile X Research and Treatment Center for over five years. She has experience as a clinical research coordinator across many types of clinical trials and served as the clinical research manager for the Cincinnati program. She earned a bachelor’s degree in psychology, a master’s, and is a SOCRA certified clinical research professional (CCRP). She enjoys time with family and friends, a great book, a strong cup of coffee and, of course, a good laugh!