My research explores the regulatory roles of RNA sequences and structures in gene expression and neurological diseases, uncovering how RNA modifications and R-loops contribute to transcriptional regulation and how their dysregulation leads to disorders such as ALS and Alzheimer’s Disease, with the ultimate goal of developing targeted therapies.

My research focuses on the regulatory role of RNA sequence and structure. As a neurologist and RNA biologist, I study the natural regulatory roles of RNA and how impairments in these processes lead to neurological diseases. I began my research by examining DNA sequences, which led to RNA sequences and now extends to nucleic acid structures. We demonstrated that DNA sequence variation in regulatory elements explains individual differences in human gene expression and developed a genetics-of-human-gene-expression approach that has been widely adopted to identify regulatory elements influencing susceptibility to complex diseases. These studies revealed the critical role of DNA variants and gene expression levels (mRNA abundance) as quantitative traits, which we analyzed using paired DNA and RNA samples sequenced from human cells. This led to our discovery of RNA sequences differing from corresponding DNA sequences, beyond known RNA editing mechanisms.

Further studies revealed that RNA modifications and structures such as R-loops, three-stranded nucleic acid formations, contribute to these differences. Using genetics, biochemistry, and mass spectrometry, we identified RNA modifications within R-loops, such as the formation of RNA abasic sites by methylpurine DNA glycosylase. These findings provide evidence that RNA sequences differing from DNA are explained by chemical modifications of ribonucleotides. Recently, my research has focused on how these RNA modifications and structures are dysregulated in neurological disorders. For example, we showed that senataxin mutations causing juvenile-onset ALS (ALS4) disrupt R-loops and the TGFβ pathway. Collaborating with NIH colleagues, we are developing allele-specific knockdown strategies for mutant senataxin to restore R-loop homeostasis.

In Alzheimer’s Disease research, we identified the noncoding RNA AANCR, which regulates APOE transcription via R-loop formation and RNA modifications. We showed that AANCR sequence variants modify Alzheimer’s Disease risk conferred by APOE4, highlighting its potential as a therapeutic target. By leveraging extensive knowledge of gene regulation, our goal is to establish the foundation for targeted Alzheimer’s Disease treatments.

Beyond research, I am deeply committed to mentoring the next generation of scientists and fostering diversity in STEMM. As a faculty member, I teach genetics to medical students, lead graduate seminar courses, and mentor a diverse group of individuals, including undergraduates, graduate students, and clinical fellows. Drawing on my personal experiences as a woman of color with a rare genetic disease, I support trainees with disabilities and those from underrepresented backgrounds, helping them achieve success. My mentorship has guided students to notable accomplishments, such as a Rhodes Scholarship recipient and faculty appointments at prestigious institutions. Additionally, I co-founded the Physician-Scientist Support Foundation to address the decline of physician-scientists by supporting students lacking research experience.  I also serve on the advisory board of the National of Academy of Medicine Emerging Leadership Program to diversify the membership of the Academy.

Elected Member, American Society for Clinical Investigation

Elected Member, Association of American Physicians 

Elected Member, National Academy of Medicine

Scientific Achievement Award, American Society of Human Genetics

American Society of Human Genetics

The RNA Society

Human RNome Project Consortiuma